CA2288994A1 - Polyalkylene oxide-modified single chain polypeptides - Google Patents

Polyalkylene oxide-modified single chain polypeptides Download PDF

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CA2288994A1
CA2288994A1 CA002288994A CA2288994A CA2288994A1 CA 2288994 A1 CA2288994 A1 CA 2288994A1 CA 002288994 A CA002288994 A CA 002288994A CA 2288994 A CA2288994 A CA 2288994A CA 2288994 A1 CA2288994 A1 CA 2288994A1
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polypeptide
antigen
chain
binding
polyalkylene oxide
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CA2288994C (en
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Marc D. Whitlow
Robert G. L. Shorr
David R. Filpula
Lihsyng S. Lee
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Enzon Pharmaceuticals Inc
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6854—Immunoglobulins
    • G01N33/6857—Antibody fragments
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
    • C07K2317/41—Glycosylation, sialylation, or fucosylation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

Abstract

The present invention relates to the chemical modification of single chain polypeptides by means of covalent attachment of strands of poly(ethylene glycol) PEG and similar poly(alkylene oxides) to single chain polypeptide binding molecules that have the three dimensional folding and, thus, the binding ability and specificity, of the variable region of an antibody. Such preparations of modified single chain polypeptide binding molecules have reduced immugenicity and antigenicity as well as having a longer halflife in the bloodstream as compared to the parent polypeptide. These beneficial properties of the modified single chain polypeptide binding molecules make them very useful in a variety of therapeutic applications. The invention also relates to multivalent antigen-binding molecules capable of PEGylation. Compositions of, genetic constructions for, methods of use, and methods for producing PEGylated antigen-binding proteins are disclosed.

Claims (63)

1. A single-chain antigen-binding polypeptide-polyalkylene oxide conjugate, comprising a single-chain antigen-binding polypeptide comprising:
(a) a first polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain;
(b) a second polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain; and (c) a peptide linker linking the first and second polypeptides (a) and (b) into a single chain polypeptide having an antigen binding site, wherein said single-chain antigen-binding polypeptide is conjugated to polyalkylene oxide and wherein said single-chain antigen-binding polypeptide-polyalkylene oxide conjugate has an antigen binding affinity within a range of about one-fold to about ten-fold of the antigen binding affinity of said single-chain antigen-binding polypeptide in its unconjugated form.
2. A single-chain antigen-binding polypeptide-polyalkylene oxide conjugate, comprising a single-chain antigen-binding polypeptide comprising:
(a) a first polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain;
(b) a second polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain; and (c) a peptide linker linking the first and second polypeptides (a) and (b) into a single chain polypeptide having an antigen binding site, wherein said single-chain antigen-binding polypeptide is conjugated to polyalkylene oxide and wherein said single-chain antigen-binding polypeptide-polyalkylene oxide conjugate has an antigen binding affinity within about ten-fold of the antigen binding affinity of said single-chain antigen-binding polypeptide in its unconjugated form.
3. A single-chain antigen-binding polypeptide-polyalkylene oxide conjugate, comprising a single-chain antigen-binding polypeptide comprising:
(a) a first polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain;
(b) a second polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain; and (c) a peptide linker linking the first and second polypeptides (a) and (b) into a single chain polypeptide having an antigen binding site, wherein said single-chain antigen-binding polypeptide is conjugated to polyalkylene oxide and wherein said single-chain antigen-binding polypeptide-polyalkylene oxide conjugate has an antigen binding affinity within about five-fold of the antigen binding affinity of said single-chain antigen-binding polypeptide in its unconjugated form.
4. A single-chain antigen-binding polypeptide-polyalkylene oxide conjugate, comprising a single-chain antigen-binding polypeptide comprising:
(a) a first polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain;
(b) a second polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain; and (c) a peptide linker linking the first and second polypeptides (a) and (b) into a single chain polypeptide having an antigen binding site, wherein said single-chain antigen-binding polypeptide is conjugated to polyalkylene oxide and wherein said single-chain antigen-binding polypeptide-polyalkylene oxide conjugate has an antigen binding affinity within about two-fold of the antigen binding amity of said single-chain antigen-binding polypeptide in its unconjugated form.
5. A single-chain antigen-binding polypeptide capable of polyalkylene oxide conjugation, comprising:
(a) a first polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain;
(b) a second polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain; and (c) a peptide linker linking said first and second polypeptides (a) and (b) into a single chain polypeptide having an antigen binding site, wherein the single-chain antigen-binding polypeptide has at least one Cys residue which is capable of polyalkylene oxide conjugation, wherein said Cys residue is located at a position selected from the group consisting of:
(i) the amino acid position 11, 12, 13, 14 or 15 of the light chain variable region;
(ii) the amino acid position 77, 78 or 79 of the light chain variable region;
(iii) the amino acid position 11, 12, 13, 14 or 15 of the heavy chain variable region;
(iv) the amino acid position 82B, 82C or 83 of the heavy chain variable region;
(v) any amino acid position of the peptide linker;
(vi) adjacent to the C-terminus of polypeptide (a) or (b); and (vii) combinations thereof, wherein the polyalkylene oxide conjugated single-chain antigen-binding polypeptide is capable of binding an antigen.
6. The single-chain antigen-binding polypeptide of claim 5, wherein said Cys residue capable of polyalkylene oxide conjugation is located at a position selected from the group consisting of:
(i') the amino acid position 77 of the light chain variable region;
(ii') the amino acid position 82B of the heavy chain variable region;
(iii') the amino acid position 3 of the peptide linker;
(iv') adjacent to the C-terminus of said polypeptide (a) or (b); and (v') combinations thereof.
7. The single-chain antigen-binding polypeptide of claim 5, wherein said first polypeptide (a) comprises the antigen binding portion of the variable region of an antibody light chain and said second polypeptide (b) comprises the antigen binding portion of the variable region of an antibody heavy chain.
8. The single-chain antigen-binding polypeptide of claim 5, wherein the C-terminus of said second polypeptide (b) is the native C-terminus.
9. The single-chain antigen-binding polypeptide of claim 5, wherein the C-terminus of said second polypeptide (b) comprises a deletion of one or plurality of amino acid residue(s), such that the remaining N-terminus amino acid residues of the second polypeptide are sufficient for the polyalkylene oxide conjugated single-chain antigen-binding polypeptide to be capable of binding an antigen.
10. The single-chain antigen-binding polypeptide of claim 5, wherein the C-terminus of said second polypeptide (b) comprises an addition of one or plurality of amino acid residue(s), such that the polyalkylene oxide conjugated single-chain antigen-binding polypeptide is capable of binding an antigen.
11. The single-chain antigen-binding polypeptide of claim 5, wherein said wherein said Cys residue capable of polyalkylene oxide conjugation is attached to a polyalkylene oxide moiety.
12. The polyalkylene oxide conjugated single-chain antigen-binding polypeptide of claim 11, wherein said polyalkylene oxide conjugated single-chain antigen-binding polypeptide is conjugated to one or plurality of peptide, lipid, nucleic acid, drug, toxin, chelator, boron addend or detectable label molecules.
13. The polyalkylene oxide conjugated single-chain antigen-binding polypeptide of claim 11, wherein said polyalkylene oxide conjugated single-chain antigen-binding polypeptide is conjugated to a carrier having one or plurality of peptide, lipid, nucleic acid, drug, toxin, chelator, boron addend or detectable label molecules bound to said carrier.
14. A polynucleotide sequence encoding a single-chain antigen-binding polypeptide capable of polyalkylene oxide conjugation, comprising:
(a) a first polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain;
(b) a second polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain; and (c) a peptide linker linking said first and second polypeptides (a) and (b) into a single chain polypeptide having an antigen binding site, wherein the single-chain antigen-binding polypeptide has at least one Cys residue which is capable of polyalkylene oxide conjugation, wherein said Cys residue is located at a position selected from the group consisting of:
(i) the amino acid position 11, 12, 13, 14 or 15 of said light chain variable region;

(ii) the amino acid position 77, 78 or 79 of said light chain variable region;
(iii) the amino acid position 11, 12, 13, 14 or 15 of said heavy chain variable region;
(iv) the amino acid position 82B, 82C or 83 of said heavy chain variable region;
(v) any amino acid position of said peptide linker;
(vi) adjacent to the C-terminus of said polypeptide (a) or (b); and (vii) combinations thereof, and wherein the polyalkylene oxide conjugated single-chain antigen-binding polypeptide is capable of binding an antigen.
15. The polynucleotide sequence of claim 14, wherein said Cys residue capable of polyalkylene oxide conjugation is located at a position selected from the group consisting of:
(i') the amino acid position 77 of the light chain variable region;
(ii') the amino acid position 82B of the heavy chain variable region;
(iii') the amino acid position 3 of the peptide linker;
(iv') adjacent to the C-terminus of said polypeptide (a) or (b); and (v') combinations thereof.
16. A replicable cloning or expression vehicle comprising the polynucleotide sequence of claim 14.
17. The vehicle of claim 16 which is a plasmid.
18. A host cell transformed with the polynucleotide of claim 17.
19. The host cell of claim 18 which is a bacterial cell, a yeast cell or other fungal cell, an insect cell or a mammalian cell line.
20. The host cell of claim 19 which is Pichia pastoris.
21. A method of a producing single-chain antigen-binding polypeptide-polyalkylene oxide conjugate, comprising a single-chain antigen-binding polypeptide comprising:
(a) providing a first genetic sequence encoding a first polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain;
(b) providing a second genetic sequence encoding a second polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain; and (c) linking the first and second genetic sequences (a) and (b) with a third genetic sequence encoding a linker into a fourth genetic sequence encoding a single chain polypeptide having an antigen binding site, wherein said single-chain antigen-binding polypeptide is capable of polyalkylene oxide conjugation and wherein said single-chain antigen-binding polypeptide-polyalkylene oxide conjugate retains antigen binding affinity within a range of about one-fold to about ten-fold of the antigen binding affinity of said single-chain antigen-binding polypeptide in its unconjugated form.
22. A method of producing a single-chain antigen-binding polypeptide capable of polyalkylene oxide conjugation, comprising:
(a) providing a first genetic sequence encoding a first polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain;
(b) providing a second genetic sequence encoding a second polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain; and (c) linking said first and second genetic sequences (a) and (b) with a third genetic sequence encoding a peptide linker into a fourth genetic sequence encoding a single chain polypeptide having an antigen binding site, wherein the single-chain antigen-binding polypeptide has at least one Cys residue which is capable of polyalkylene oxide conjugation, wherein said Cys residue is located at a position selected from the group consisting of:
(i) the amino acid position 11, 12, 13, 14 or 15 of said light chain variable region;
(ii) the amino acid position 77, 78 or 79 of said light chain variable region;
(iii) the amino acid position 11, 12, 13, 14 or 15 of said heavy chain variable region;
(iv) the amino acid position 82B, 82C or 83 of said heavy chain variable region;
(v) any amino acid position of said peptide linker;
(vi) adjacent to the C-terminus of said polypeptide (a) or (b); and (vii) combinations thereof, and wherein the polyalkylene oxide conjugated single-chain antigen-binding polypeptide is capable of binding an antigen;
(d) transforming a host cell with said fourth genetic sequence encoding said single-chain antigen-binding polypeptide of step (c); and (e) expressing said single-chain antigen-binding polypeptide of step (c) in said host, thereby producing a single-chain antigen-binding polypeptide capable of polyalkylene oxide conjugation.
23. The method of claim 22, wherein said Cys residue capable of polyalkylene oxide conjugation is located at a position selected from the group consisting of (i') the amino acid position 77 of the light chain variable region;
(ii') the amino acid position 82B of the heavy chain variable region;

(iii') the amino acid position 3 of the peptide linker;
(iv') adjacent to the C-terminus of said polypeptide (a) or (b); and (v') combinations thereof.
24. The method of claim 22, said first genetic sequence encoding a first polypeptide (a) comprises the antigen binding portion of the variable region of an antibody light chain and said second genetic sequence encoding a second polypeptide (b) comprises the antigen binding portion of the variable region of an antibody heavy chain.
25. The method of claim 22, wherein the C-terminus of said second polypeptide (b) is the native C-terminus.
26. The method of claim 22, wherein the C-terminus of said second polypeptide (b) comprises a deletion of one or plurality of amino acid residue(s), such that the remaining N-terminus amino acid residues of the second polypeptide are sufficient for the polyalkylene oxide conjugated single-chain antigen-binding polypeptide to be capable of binding an antigen.
27. The method of claim 22, wherein the C-terminus of said second polypeptide (b) comprises an addition of one or plurality of amino acid residue(s), such that the polyalkylene oxide conjugated single-chain antigen-binding polypeptide is capable of binding an antigen.
28. A multivalent single-chain antigen-binding polypeptide-polyalkylene oxide conjugate, comprising two or more single-chain antigen binding polypeptides, each single-chain antigen-binding polypeptide comprising:
(a) a first polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain;

(b) a second polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain; and (c) a peptide linker linking the first and second polypeptides (a) and (b) into a single chain polypeptide having an antigen binding site, wherein said single-chain antigen-binding polypeptide is conjugated to polyalkylene oxide and wherein said single-chain antigen-binding polypeptide-polyalkylene oxide conjugate retains antigen binding affinity within a range of about one-fold to about ten-fold of the antigen binding affinity of said single-chain antigen-binding polypeptide in its unconjugated form.
29. A multivalent single-chain antigen-binding protein, comprising two or more single-chain antigen-binding polypeptides, each single-chain antigen-binding polypeptide comprising:
(a) a first polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain;
(b) a second polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain; and (c) a peptide linker linking said first and second polypeptides wherein one of the two single-chain antigen-binding polypeptide has at least one Cys residue which is capable of polyalkylene oxide conjugation, wherein said Cys residue is located at a position selected from the group consisting of:
(i) the amino acid position 11, 12, 13, 14 or 15 of said light chain variable region;
(ii) the amino acid position 77, 78 or 79 of said light chain variable region;
(iii) the amino acid position 11, 12, I3, 14 or 15 of said heavy chain variable region;
(iv) the amino acid position 82B, 82C or 83 of said heavy chain variable region;

(v) any amino acid position of said peptide linker;
(vi) adjacent to the C-terminus of said polypeptide (a) or (b); and (vii) combinations thereof, and wherein the polyalkylene oxide conjugated single-chain antigen-binding polypeptide is capable of binding an antigen.
30. The multivalent protein of claim 29, wherein said Cys residue capable of polyalkylene oxide conjugation is located at a position selected from the group consisting of:
(i') the amino acid position 77 of the light chain variable region;
{ii') the amino acid position 82B of the heavy chain variable region;
(iii') the amino acid position 3 of the peptide linker;
(iv') adjacent to the C-terminus of said polypeptide (a) or (b); and (v') combinations thereof.
31. The multivalent protein of claim 29, wherein said first polypeptide (a) comprises the antigen binding portion of the variable region of an antibody light chain and said second polypeptide (b) comprises the antigen binding portion of the variable region of an antibody heavy chain.
32. The multivalent protein of claim 29, wherein the C-terminus of said second polypeptide (b) is the native C-terminus.
33. The multivalent protein of claim 29, wherein the C-terminus of said second polypeptide (b) comprises a deletion of one or plurality of amino acid residue(s), such that the remaining N-terminus amino acid residues of the second polypeptide are sufficient for the polyalkylene oxide conjugated single-chain antigen-binding polypeptide to be capable of binding an antigen.
34. The multivalent protein of claim 29, wherein the C-terminus of said second polypeptide comprises an addition of one or plurality of amino acid residue(s), such that the polyalkylene oxide conjugated single-chain antigen-binding polypeptide is capable of binding an antigen.
35. The multivalent protein of claim 29, wherein said wherein said Cys residue capable of polyalkylene oxide conjugation is attached to a polyalkylene oxide moiety.
36. The polyalkylene oxide conjugated multivalent protein of claim 35, wherein said polyalkylene oxide conjugated multivalent protein is conjugated to one or plurality of peptide, lipid, nucleic acid, drug, toxin, chelator, boron addend or detectable label molecule(s).
37. A method of detecting an antigen suspected of being in a sample, comprising:
(a) contacting said sample with the polyalkylene oxide conjugated polypeptide or protein of claim 1 or 11, wherein said polyalkylene oxide conjugated polypeptide or protein is conjugated to one or plurality of detectable label molecule(s), or conjugated to a carrier having one or plurality of detectable label molecules) bound to said carrier; and (b) detecting whether said polyalkylene oxide conjugated single-chain antigen-binding polypeptide or protein has bound to said antigen.
38. A method of imaging the internal structure of an animal, comprising administering to said animal an effective amount of the polyalkylene oxide conjugated polypeptide or protein of claim 1 or 11, wherein said polyalkylene oxide conjugated polypeptide or protein is conjugated to one or plurality of detectable label or chelator molecule(s), or conjugated to a carrier having one or plurality of detectable label or chelator molecule(s) bound to said carrier, and measuring detectable radiation associated with said animal.
39. The method of claim 38, wherein said animal includes a human.
40. A method for treating a targeted disease, comprising administering an effective amount of a composition comprising the polyalkylene oxide conjugated polypeptide or protein of claim 1 or 11 and a pharmaceutically acceptable carrier vehicle, wherein said polyalkylene oxide conjugated polypeptide or protein is conjugated to one or plurality of peptide, lipid, nucleic acid, drug, toxin, boron addend or radioisotope molecule(s), or conjugated to a carrier having one or plurality of peptide, lipid, nucleic acid, drug, toxin, boron addend or radioisotope molecule(s) bound to said carrier.
41. A single-chain antigen-binding polypeptide capable of polyalkylene oxide conjugation, comprising:
(a) a first polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain;
(b) a second polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain; and (c) a peptide linker linking the first and second polypeptides (a) and (b) into a single chain polypeptide having an antigen binding site, wherein the single-chain antigen-binding polypeptide has at least three consecutive Lys residues which are capable of polyalkylene oxide conjugation and wherein any one of said consecutive Lys residues is located at a position selected from the group consisting of (i) any amino acid position of the peptide linker;
(ii) adjacent to the C-terminus of the second polypeptide (b); and (iii) combinations thereof, wherein the polyalkylene oxide conjugated single-chain antigen-binding polypeptide is capable of binding an antigen.
42. A polynucleotide sequence encoding a single-chain antigen-binding polypeptide capable of polyalkylene oxide conjugation, comprising:
(a) a first polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain;
(b) a second polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain; and (c) a peptide linker linking the first and second polypeptides (a) and (b) into a single chain polypeptide having an antigen binding site, wherein the single-chain antigen-binding polypeptide has at least three consecutive Lys residues which are capable of polyalkylene oxide conjugation and wherein any one of said consecutive Lys residues is located at a position selected from the group consisting of (i) any amino acid position of the peptide linker;
(ii) adjacent to the C-terminus of the second polypeptide (b); and (iii) combinations thereof, wherein the polyalkylene oxide conjugated single-chain antigen-binding polypeptide is capable of binding an antigen.
43. A replicable cloning or expression vehicle comprising the polynucleotide sequence of claim 42.
44. The vehicle of claim 43 which is a plasmid.
45. A host cell transformed with the polynucleotide of claim 42.
46. The host cell of claim 39 which is a bacterial cell, a yeast cell or other fungal cell, an insect cell or a mammalian cell line.
47. The host cell of claim 46 which is Pichia pastoris.
48. A method of producing a single-chain antigen-binding polypeptide capable of polyalkylene oxide conjugation, comprising:
{a) a first polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain;
(b) a second polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain; and (c) a peptide linker linking the first and second polypeptides (a) and (b) into a single chain polypeptide having an antigen binding site, wherein the single-chain antigen-binding polypeptide has at least three consecutive Lys residues which are capable of polyalkylene oxide conjugation and wherein any one of said consecutive Lys residues is located at a position selected from the group consisting of (i) any amino acid position of the peptide linker;
(ii) adjacent to the C-terminus of the second polypeptide (b); and (iii) combinations thereof, wherein the polyalkylene oxide conjugated single-chain antigen-binding polypeptide is capable of binding an antigen.
49. The single-chain antigen-binding polypeptide of claim 41, wherein said wherein said wherein any one of said consecutive Lys residues capable of polyalkylene oxide conjugation is attached to a polyalkylene oxide moiety.
50. The polyalkylene oxide conjugated single-chain antigen-binding polypeptide of claim 49, wherein said polyalkylene oxide conjugated single-chain antigen-binding polypeptide is conjugated to one or plurality of peptide, lipid, nucleic acid, drug, toxin, chelator, boron addend or detectable label molecules.
51. The polyalkylene oxide conjugated single-chain antigen-binding polypeptide of claim 49, wherein said polyalkylene oxide conjugated single-chain antigen-binding polypeptide is conjugated to a carrier having one or plurality of peptide, lipid, nucleic acid, drug, toxin, chelator, boron addend or detectable label molecules bound to said carrier.
52. A method of producing a single-chain antigen-binding polypeptide capable of polyalkylene oxide conjugation, comprising:
(a) providing a first genetic sequence encoding a first polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain;
(b) providing a second genetic sequence encoding a second polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain; and (c) linking said first and second genetic sequences (a) and (b) with a third genetic sequence encoding a peptide linker into a fourth genetic sequence encoding a single chain polypeptide having an antigen binding site, wherein the single-chain antigen-binding polypeptide has at least three consecutive Lys residues which are capable of polyalkylene oxide conjugation and wherein any one of said consecutive Lys residues is located at a position selected from the group consisting of (i) any amino acid position of the peptide linker;
(ii) adjacent to the C-terminus of the second polypeptide (b); and (iii) combinations thereof, wherein the polyalkylene oxide conjugated single-chain antigen-binding polypeptide is capable of binding an antigen;
(d) transforming a host cell with said fourth genetic sequence encoding said single-chain antigen-binding polypeptide of step (c); and (e) expressing said single-chain antigen-binding polypeptide of step (c) in said host, thereby producing a single-chain antigen-binding polypeptide capable of polyalkylene oxide conjugation.
53. The method of claim 52, said first genetic sequence encoding a first polypeptide (a) comprises the antigen binding portion of the variable region of an antibody light chain and said second genetic sequence encoding a second polypeptide (b) comprises the antigen binding portion of the variable region of an antibody heavy chain.
54. The method of claim 52, wherein the C-terminus of said second polypeptide (b) is the native C-terminus.
55. The method of claim 52, wherein the C-terminus of said second polypeptide (b) comprises a deletion of one or plurality of amino acid residue(s), such that the remaining N-terminus amino acid residues of the second polypeptide are sufficient for the polyalkylene oxide conjugated single-chain antigen-binding polypeptide to be capable of binding an antigen.
56. The method of claim 52, wherein the C-terminus of said second polypeptide (b) comprises an addition of one or plurality of amino acid residue(s), such that the polyalkylene oxide conjugated single-chain antigen-binding polypeptide is capable of binding an antigen.
57. A multivalent single-chain antigen-binding protein, comprising two or more single-chain antigen-binding polypeptides, each single-chain antigen-binding polypeptide comprising:
(a) a first polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain;

(b) a second polypeptide comprising the antigen binding portion of the variable region of an antibody heavy or light chain; and (c) a peptide linker linking said first and second polypeptides wherein one of the two single-chain antigen-binding polypeptides has at least three consecutive Lys residues which are capable of polyalkylene oxide conjugation and wherein any one of said consecutive Lys residues is located at a position selected from the group consisting of (i) any amino acid position of the peptide linker;
(ii) adjacent to the C-terminus of the second polypeptide (b); and (iii) combinations thereof, wherein the polyalkylene oxide conjugated single-chain antigen-binding polypeptide is capable of binding an antigen.
58. The multivalent protein of claim 57, wherein said first polypeptide (a) comprises the antigen binding portion of the variable region of an antibody light chain and said second polypeptide (b) comprises the antigen binding portion of the variable region of an antibody heavy chain.
59. The multivalent protein of claim 57, wherein the C-terminus of said second polypeptide (b) is the native C-terminus.
60. The multivalent protein of claim 57, wherein the C-terminus of said second polypeptide (b) comprises a deletion of one or plurality of amino acid residue(s), such that the remaining N-terminus amino acid residues of the second polypeptide are sufficient for the polyalkylene oxide conjugated single-chain antigen-binding polypeptide to be capable of binding an antigen.
61. The multivalent protein of claim 57, wherein the C-terminus of said second polypeptide comprises an addition of one or plurality of amino acid residue(s), such that the polyalkylene oxide conjugated single-chain antigen-binding polypeptide is capable of binding an antigen.
62. The multivalent protein of claim 57, wherein any one of said consecutive Lys residues capable of polyalkylene oxide conjugation is attached to a polyalkylene oxide moiety.
63. The polyalkylene oxide conjugation multivalent protein of claim 62, wherein said polyalkylene oxide conjugated multivalent protein is conjugated to one or plurality of peptide, lipid, nucleic acid, drug, toxin, chelator, boron addend or detectable label molecule(s).
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Families Citing this family (364)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002505574A (en) * 1997-04-30 2002-02-19 エンゾン，インコーポレイテッド Polyalkylene oxide-modified single-chain polypeptides
US20040009166A1 (en) * 1997-04-30 2004-01-15 Filpula David R. Single chain antigen-binding polypeptides for polymer conjugation
US6333396B1 (en) 1998-10-20 2001-12-25 Enzon, Inc. Method for targeted delivery of nucleic acids
ES2257094T3 (en) * 1998-11-03 2006-07-16 Centocor, Inc. MODIFIED ANTIBODIES AND ANTIBODY FRAGMENTS WITH INCREASED DURATION OF ACTIVITY.
US7122632B2 (en) 1999-12-23 2006-10-17 Zymogenetics, Inc. Soluble Interleukin-20 receptor
US6610286B2 (en) 1999-12-23 2003-08-26 Zymogenetics, Inc. Method for treating inflammation using soluble receptors to interleukin-20
DE60139110D1 (en) 2000-01-10 2009-08-13 Maxygen Holdings Ltd G-CSF CONJUGATES
DK1257295T3 (en) 2000-02-11 2009-08-10 Bayer Healthcare Llc Factor VII or VIIA-like molecules
US20030027207A1 (en) * 2000-02-29 2003-02-06 Filpula David Ray Anti-platelet binding proteins and polymer conjugates containing the same
US6410246B1 (en) * 2000-06-23 2002-06-25 Genetastix Corporation Highly diverse library of yeast expression vectors
US6410271B1 (en) * 2000-06-23 2002-06-25 Genetastix Corporation Generation of highly diverse library of expression vectors via homologous recombination in yeast
US7118737B2 (en) * 2000-09-08 2006-10-10 Amylin Pharmaceuticals, Inc. Polymer-modified synthetic proteins
EP1318827A4 (en) * 2000-09-08 2005-09-14 Gryphon Therapeutics Inc Polymer-modified synthetic proteins
US20070141135A1 (en) * 2005-06-29 2007-06-21 Balu-Lyer Sathy V Compositions and methods for less immunogenic protein-lipid complexes
US8110218B2 (en) * 2000-11-30 2012-02-07 The Research Foundation Of State University Of New York Compositions and methods for less immunogenic protein-lipid complexes
WO2002044197A2 (en) * 2000-12-01 2002-06-06 Fish Eleanor N Cytokine receptor binding peptides
US6979556B2 (en) 2000-12-14 2005-12-27 Genentech, Inc. Separate-cistron contructs for secretion of aglycosylated antibodies from prokaryotes
US7195923B2 (en) * 2001-01-31 2007-03-27 Scripps Laboratories, Inc. Ratiometric determination of glycated protein
DE60232434D1 (en) 2001-02-27 2009-07-09 Maxygen Aps NEW INTERFERON-BETA-LIKE MOLECULES
US20030077739A1 (en) 2001-08-27 2003-04-24 Genentech, Inc. System for antibody expression and assembly
US7157277B2 (en) 2001-11-28 2007-01-02 Neose Technologies, Inc. Factor VIII remodeling and glycoconjugation of Factor VIII
US7173003B2 (en) 2001-10-10 2007-02-06 Neose Technologies, Inc. Granulocyte colony stimulating factor: remodeling and glycoconjugation of G-CSF
US7795210B2 (en) * 2001-10-10 2010-09-14 Novo Nordisk A/S Protein remodeling methods and proteins/peptides produced by the methods
US7214660B2 (en) 2001-10-10 2007-05-08 Neose Technologies, Inc. Erythropoietin: remodeling and glycoconjugation of erythropoietin
US8008252B2 (en) 2001-10-10 2011-08-30 Novo Nordisk A/S Factor VII: remodeling and glycoconjugation of Factor VII
AU2004236174B2 (en) 2001-10-10 2011-06-02 Novo Nordisk A/S Glycopegylation methods and proteins/peptides produced by the methods
CA2467723C (en) 2001-12-17 2011-09-27 Zymogenetics, Inc. Method for treating cervical cancer
WO2003062278A1 (en) 2002-01-25 2003-07-31 G2 Therapies Ltd MONOCLONAL ANTIBODIES AGAINST EXTRACELLULAR LOOPS OF C5aR
PL211175B1 (en) 2002-06-21 2012-04-30 Novo Nordisk Healthcare Ag Pegylated factor vii glycoforms
DE60336555D1 (en) 2002-06-21 2011-05-12 Novo Nordisk Healthcare Ag PEGYLATED GLYCO FORMS OF FACTOR VII
US9321832B2 (en) 2002-06-28 2016-04-26 Domantis Limited Ligand
US20050026866A1 (en) * 2002-08-02 2005-02-03 Pawelek John M. Agents and methods for treatment of disease by oligosaccharide targeting agents
US20040067532A1 (en) 2002-08-12 2004-04-08 Genetastix Corporation High throughput generation and affinity maturation of humanized antibody
WO2004020673A1 (en) * 2002-08-28 2004-03-11 Millipore Corporation Compositions of solution for sequencing reaction clean-up
US20040062748A1 (en) * 2002-09-30 2004-04-01 Mountain View Pharmaceuticals, Inc. Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof
US8129330B2 (en) 2002-09-30 2012-03-06 Mountain View Pharmaceuticals, Inc. Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof
EP1616003A4 (en) 2002-12-30 2007-06-20 Gryphon Therapeutics Inc Water-soluble thioester and selenoester compounds and methods for making and using the same
US7351688B2 (en) * 2003-02-05 2008-04-01 The Research Foundation Of State University Of New York Compositions and methods for less immunogenic protein formulations
WO2004071420A2 (en) * 2003-02-05 2004-08-26 The Research Foundation Of State University Of New York Compositions and methods for less immunogenic protein formulations
CA2519092C (en) 2003-03-14 2014-08-05 Neose Technologies, Inc. Branched water-soluble polymers and their conjugates
US8791070B2 (en) 2003-04-09 2014-07-29 Novo Nordisk A/S Glycopegylated factor IX
ES2380093T3 (en) * 2003-05-09 2012-05-08 Biogenerix Ag Compositions and methods for the preparation of human growth hormone glycosylation mutants
AU2004220325B2 (en) * 2003-06-30 2011-05-12 Domantis Limited Polypeptides
WO2005012484A2 (en) * 2003-07-25 2005-02-10 Neose Technologies, Inc. Antibody-toxin conjugates
WO2005017526A1 (en) * 2003-08-05 2005-02-24 The Research Foundation Of State University Of New York Reconstitution medium for protein and peptide formulations
US20050055024A1 (en) * 2003-09-08 2005-03-10 James Anthony H. Orthopaedic implant and screw assembly
WO2005035565A1 (en) 2003-10-10 2005-04-21 Novo Nordisk A/S Il-21 derivatives
ES2428358T3 (en) 2003-10-17 2013-11-07 Novo Nordisk A/S Combination therapy
ATE447587T1 (en) * 2003-11-21 2009-11-15 Zymogenetics Inc ANTI-IL-20 ANTIBODIES AND BINDING PARTNERS AND METHOD FOR USE IN INFLAMMATION
US8633157B2 (en) 2003-11-24 2014-01-21 Novo Nordisk A/S Glycopegylated erythropoietin
US20080305992A1 (en) 2003-11-24 2008-12-11 Neose Technologies, Inc. Glycopegylated erythropoietin
US7842661B2 (en) 2003-11-24 2010-11-30 Novo Nordisk A/S Glycopegylated erythropoietin formulations
US20060040856A1 (en) 2003-12-03 2006-02-23 Neose Technologies, Inc. Glycopegylated factor IX
US7956032B2 (en) 2003-12-03 2011-06-07 Novo Nordisk A/S Glycopegylated granulocyte colony stimulating factor
US20080220049A1 (en) * 2003-12-05 2008-09-11 Adnexus, A Bristol-Myers Squibb R&D Company Compositions and methods for intraocular delivery of fibronectin scaffold domain proteins
KR20060129246A (en) 2003-12-05 2006-12-15 컴파운드 쎄라퓨틱스, 인크. Inhibitors of type 2 vascular endothelial growth factor receptors
CN101072789B (en) 2004-01-08 2013-05-15 生物种属学股份公司 O-linked glycosylation of peptides
WO2005074524A2 (en) 2004-02-02 2005-08-18 Ambrx, Inc. Modified human interferon polypeptides and their uses
AU2005319099B2 (en) 2004-02-02 2010-09-16 Ambrx, Inc. Modified human growth hormone
KR101699142B1 (en) 2004-06-18 2017-01-23 암브룩스, 인코포레이티드 Novel antigen-binding polypeptides and their uses
WO2006010143A2 (en) 2004-07-13 2006-01-26 Neose Technologies, Inc. Branched peg remodeling and glycosylation of glucagon-like peptide-1 [glp-1]
US20090292110A1 (en) * 2004-07-23 2009-11-26 Defrees Shawn Enzymatic modification of glycopeptides
US20060045866A1 (en) * 2004-09-01 2006-03-02 Chris Chappelow Novel high purity and high molecular weight mPEG alcohol compositions
EP1799249A2 (en) 2004-09-10 2007-06-27 Neose Technologies, Inc. Glycopegylated interferon alpha
EP1814573B1 (en) 2004-10-29 2016-03-09 ratiopharm GmbH Remodeling and glycopegylation of fibroblast growth factor (fgf)
MX2007007587A (en) 2004-12-22 2007-12-11 Ambrx Inc Formulations of human growth hormone comprising a non-naturally encoded amino acid.
JP4990792B2 (en) 2004-12-22 2012-08-01 アンブレツクス・インコーポレイテツド Compositions of aminoacyl-tRNA synthetases and uses thereof
CN103290084A (en) 2004-12-22 2013-09-11 Ambrx公司 Method for expression and purification of recombinant human growth hormone
NZ556436A (en) 2005-01-10 2010-11-26 Biogenerix Ag Glycopegylated granulocyte colony stimulating factor
EP1841787A2 (en) * 2005-01-25 2007-10-10 Cell Therapeutics, Inc. Conjugates of biologically active proteins having a modified in vivo half-life
JP2008533114A (en) * 2005-03-18 2008-08-21 ユーシーエル ビジネス パブリック リミテッド カンパニー Mechano growth factor peptides and uses thereof
US20060233740A1 (en) * 2005-03-23 2006-10-19 Bossard Mary J Conjugates of an hGH moiety and a polymer
EP1868652A2 (en) 2005-04-05 2007-12-26 Istituto di Richerche di Biologia Molecolare P. Angeletti S.p.A. Method for shielding functional sites or epitopes on proteins
US9187546B2 (en) 2005-04-08 2015-11-17 Novo Nordisk A/S Compositions and methods for the preparation of protease resistant human growth hormone glycosylation mutants
JP5216580B2 (en) 2005-05-25 2013-06-19 ノヴォ ノルディスク アー／エス Glycopegylated factor IX
US20110003744A1 (en) * 2005-05-25 2011-01-06 Novo Nordisk A/S Glycopegylated Erythropoietin Formulations
JP2008541769A (en) 2005-06-03 2008-11-27 アンブレツクス・インコーポレイテツド Improved human interferon molecules and their use
US8028453B2 (en) * 2005-06-16 2011-10-04 Hold That Thought, Inc. Apparatus and methods for displaying a card
ES2553160T3 (en) 2005-06-17 2015-12-04 Novo Nordisk Health Care Ag Selective reduction and derivatization of engineered Factor VII proteins comprising at least one non-native cysteine
US7695710B2 (en) * 2005-06-20 2010-04-13 Pepgen Corporation Antitumor and antiviral combination therapies using low-toxicity, long-circulating human interferon-alpha analogs
JP2008543943A (en) * 2005-06-20 2008-12-04 ペプゲン コーポレイション Low toxicity long-circulating chimeras of human interferon alpha analogues and interferon tau
WO2007021822A2 (en) * 2005-08-09 2007-02-22 The Research Foundation Of State Of University Of New York At Buffalo Compositions and methods of preparation of liposomal microparticulate il-12
US20070105755A1 (en) 2005-10-26 2007-05-10 Neose Technologies, Inc. One pot desialylation and glycopegylation of therapeutic peptides
WO2007026972A2 (en) * 2005-09-01 2007-03-08 Canon Kabushiki Kaisha Binding protein molecule
US8168592B2 (en) 2005-10-21 2012-05-01 Amgen Inc. CGRP peptide antagonists and conjugates
US20090048440A1 (en) 2005-11-03 2009-02-19 Neose Technologies, Inc. Nucleotide Sugar Purification Using Membranes
CA2626522A1 (en) 2005-11-16 2007-05-24 Ambrx, Inc. Methods and compositions comprising non-natural amino acids
AU2007235463B2 (en) * 2006-03-30 2012-11-22 The Research Foundation Of State University Of New York Compositions of less immunogenic and long-circulating protein-lipid complexes
US7875288B2 (en) * 2006-03-30 2011-01-25 The Research Foundation Of State University Of New York Method for treating blood coagulation disorders
US7985839B2 (en) * 2006-03-31 2011-07-26 Baxter International Inc. Factor VIII polymer conjugates
US7982010B2 (en) * 2006-03-31 2011-07-19 Baxter International Inc. Factor VIII polymer conjugates
US7645860B2 (en) * 2006-03-31 2010-01-12 Baxter Healthcare S.A. Factor VIII polymer conjugates
KR20080108147A (en) 2006-03-31 2008-12-11 백스터 인터내셔널 인코포레이티드 Pegylated factor viii
EP2004231A4 (en) 2006-04-07 2013-07-10 Nektar Therapeutics Conjugates of an anti-tnf-alpha antibody
CA2653748A1 (en) 2006-05-02 2007-11-15 Allozyne, Inc. Non-natural amino acid substituted polypeptides
US20080096819A1 (en) * 2006-05-02 2008-04-24 Allozyne, Inc. Amino acid substituted molecules
CN101484576A (en) 2006-05-24 2009-07-15 诺沃-诺迪斯克保健股份有限公司 Factor IX analogues having prolonged in vivo half life
ES2656359T3 (en) 2006-06-30 2018-02-26 Novo Nordisk A/S Anti-NKG2A antibodies and uses thereof
JP2009544327A (en) 2006-07-21 2009-12-17 ノヴォ ノルディスク アー／エス Glycosylation of peptides with O-linked glycosylation sequences
CN106008699A (en) 2006-09-08 2016-10-12 Ambrx公司 Modified human plasma polypeptide or Fc scaffolds and their uses
JP5399906B2 (en) 2006-09-08 2014-01-29 アンブルックス，インコーポレイテッド Hybrid suppressor TRNA for vertebrate cells
JP2008069073A (en) * 2006-09-12 2008-03-27 Yokohama Tlo Co Ltd Lactoferrin conjugate and its manufacturing method
WO2008034124A2 (en) * 2006-09-15 2008-03-20 Enzon Pharmaceuticals, Inc. Targeted polymeric prodrugs containing multifunctional linkers
US8367065B2 (en) * 2006-09-15 2013-02-05 Enzon Pharmaceuticals, Inc. Targeted polymeric prodrugs containing multifunctional linkers
US7985783B2 (en) 2006-09-21 2011-07-26 The Regents Of The University Of California Aldehyde tags, uses thereof in site-specific protein modification
JP2010505874A (en) 2006-10-03 2010-02-25 ノヴォ ノルディスク アー／エス Purification method for polypeptide conjugates
KR20090110295A (en) 2006-11-22 2009-10-21 에드넥서스, 어 브리스톨-마이어스 스퀴브 알＆디 컴파니 Targeted therapeutics based on engineered proteins for tyrosine kinases receptors, including igf-ir
DK2101821T3 (en) 2006-12-15 2014-10-06 Baxter Healthcare Sa Factor VIIA (poly) sialic acid conjugate with extended half-life in vivo
EP2896630B1 (en) * 2007-01-30 2020-12-23 Epivax, Inc. Regulatory t cell epitopes, compositions and uses thereof
WO2008097497A2 (en) * 2007-02-02 2008-08-14 Adnexus, A Bristol-Myers Squibb R & D Company Vegf pathway blockade
CN107501407B (en) 2007-03-30 2022-03-18 Ambrx公司 Modified FGF-21 polypeptides and uses thereof
KR20150064246A (en) 2007-04-03 2015-06-10 바이오제너릭스 게엠베하 Methods of treatment using glycopegylated g―csf
AU2008247815B2 (en) 2007-05-02 2012-09-06 Ambrx, Inc. Modified interferon beta polypeptides and their uses
JP5876649B2 (en) 2007-06-12 2016-03-02 ラツィオファルム ゲーエムベーハーｒａｔｉｏｐｈａｒｍ ＧｍｂＨ Improved process for producing nucleotide sugars
US7968811B2 (en) * 2007-06-29 2011-06-28 Harley-Davidson Motor Company Group, Inc. Integrated ignition and key switch
EP2173380A4 (en) * 2007-07-13 2011-08-31 Abbott Biotech Ltd METHODS AND COMPOSITIONS FOR PULMONARY ADMINISTRATION OF A TNFa INHIBITOR
CA2707840A1 (en) * 2007-08-20 2009-02-26 Allozyne, Inc. Amino acid substituted molecules
AU2008289441A1 (en) 2007-08-22 2009-02-26 Cytomx Therapeutics, Inc. Activatable binding polypeptides and methods of identification and use thereof
US8207112B2 (en) 2007-08-29 2012-06-26 Biogenerix Ag Liquid formulation of G-CSF conjugate
US8877688B2 (en) 2007-09-14 2014-11-04 Adimab, Llc Rationally designed, synthetic antibody libraries and uses therefor
WO2009036379A2 (en) 2007-09-14 2009-03-19 Adimab, Inc. Rationally designed, synthetic antibody libraries and uses therefor
EP2219472B1 (en) * 2007-11-15 2011-08-03 Nestec S.A. Production of food products with enhanced in mouth and mental refreshment
NZ603812A (en) 2007-11-20 2014-06-27 Ambrx Inc Modified insulin polypeptides and their uses
DK2222706T4 (en) 2007-12-14 2016-11-21 Novo Nordisk As Antibodies that bind to NKG2D and its use
US9097667B2 (en) * 2007-12-14 2015-08-04 Biotium, Inc. Fluorescent compounds
CA2712220A1 (en) 2008-01-24 2009-07-30 Novo Nordisk A/S Humanized anti-human nkg2a monoclonal antibody
NZ620606A (en) 2008-02-08 2015-08-28 Ambrx Inc Modified leptin polypeptides and their uses
AU2009213141A1 (en) 2008-02-14 2009-08-20 Bristol-Myers Squibb Company Targeted therapeutics based on engineered proteins that bind EGFR
WO2009103113A1 (en) 2008-02-20 2009-08-27 G2 Inflammation Pty Ltd HUMANIZED ANTI-C5aR ANTIBODIES
CN103497246B (en) 2008-02-27 2016-08-10 诺沃—诺迪斯克有限公司 The Factor VlII molecule puted together
PE20091931A1 (en) 2008-05-22 2009-12-31 Bristol Myers Squibb Co MULTIVALENT FIBRONECTIN-BASED FRAME DOMAIN PROTEINS
PE20110426A1 (en) 2008-07-23 2011-07-01 Ambrx Inc MODIFIED BOVINE G-CSF POLYPEPTIDES
CN107022020A (en) 2008-09-26 2017-08-08 Ambrx公司 The animal erythropoietin polypeptides and its purposes of modification
CN102224238B (en) 2008-09-26 2015-06-10 Ambrx公司 Non-natural amino acid replication-dependent microorganisms and vaccines
US8927694B2 (en) 2008-11-18 2015-01-06 Merrimack Pharmaceuticals, Inc. Human serum albumin linkers and conjugates thereof
TWI496582B (en) 2008-11-24 2015-08-21 必治妥美雅史谷比公司 Bispecific egfr/igfir binding molecules
PT2379600E (en) 2008-12-22 2014-04-29 Novo Nordisk As Antibodies against tissue factor pathway inhibitor
CN106995495A (en) 2009-01-12 2017-08-01 希托马克斯医疗有限责任公司 Modified antibodies composition and its preparation and application
ES2539045T3 (en) 2009-01-19 2015-06-25 Innate Pharma Anti-KIR3D antibodies
RU2011138951A (en) 2009-02-23 2013-03-27 Сайтомкс Терапьютикс, Инк. PROTEINS AND WAYS OF THEIR APPLICATION
US8067201B2 (en) * 2009-04-17 2011-11-29 Bristol-Myers Squibb Company Methods for protein refolding
JP2012531197A (en) * 2009-06-25 2012-12-10 デュポン ニュートリション バイオサイエンシーズ エーピーエス protein
BR112012000032A2 (en) 2009-07-03 2016-03-15 Bionor Immuno As innovative therapeutic and diagnostic means
NZ623810A (en) 2009-07-27 2015-10-30 Lipoxen Technologies Ltd Glycopolysialylation of non-blood coagulation proteins
AU2010277438B2 (en) 2009-07-27 2015-08-20 Baxalta GmbH Glycopolysialylation of non-blood coagulation proteins
US8809501B2 (en) 2009-07-27 2014-08-19 Baxter International Inc. Nucleophilic catalysts for oxime linkage
US8642737B2 (en) 2010-07-26 2014-02-04 Baxter International Inc. Nucleophilic catalysts for oxime linkage
CN102497884A (en) * 2009-07-27 2012-06-13 巴克斯特国际公司 Blood coagulation protein conjugates
US20120283415A1 (en) 2009-09-10 2012-11-08 Ucb Pharma S.A. Multivalent Antibodies
US8658434B2 (en) * 2009-10-28 2014-02-25 Biotium, Inc. Fluorescent pyrene compounds
GB0920127D0 (en) * 2009-11-17 2009-12-30 Ucb Pharma Sa Antibodies
CA2784793A1 (en) 2009-12-21 2011-07-21 Ambrx, Inc. Modified bovine somatotropin polypeptides and their uses
CA2784800A1 (en) 2009-12-21 2011-07-21 Ambrx, Inc. Modified porcine somatotropin polypeptides and their uses
TWI513466B (en) 2010-01-20 2015-12-21 Boehringer Ingelheim Int Anticoagulant antidotes
WO2011100508A2 (en) * 2010-02-12 2011-08-18 Arizona Board Of Regents For And On Behalf Of Arizona State University Methods and compositions related to glycoprotein-immunoglobulin fusions
CA2789061A1 (en) 2010-02-26 2011-09-01 Henrik Parshad Stable antibody containing compositions
CA2791841C (en) 2010-03-05 2023-01-03 Rigshospitalet Chimeric inhibitor molecules of complement activation
TW201138808A (en) 2010-05-03 2011-11-16 Bristol Myers Squibb Co Serum albumin binding molecules
JP2013528374A (en) 2010-05-10 2013-07-11 パーシード セラピューティクス リミテッド ライアビリティ カンパニー Polypeptide inhibitors of VLA4
WO2011150133A2 (en) 2010-05-26 2011-12-01 Bristol-Myers Squibb Company Fibronectin based scaffold proteins having improved stability
CN105055306B (en) 2010-05-28 2019-10-01 诺沃—诺迪斯克有限公司 Stable multi-dose compositions comprising antibody and preservative
EP3443981B1 (en) 2010-06-29 2021-03-10 Centre National de la Recherche Scientifique (CNRS) Llt-1 antibodies with new functional properties
CN103080135B (en) 2010-06-30 2017-06-13 诺沃—诺迪斯克有限公司 The antibody of tissue factor approach restrainer can be specifically bound
DK3741883T3 (en) 2010-07-16 2023-02-20 Adimab Llc ANTIBODIES LIBRARIES
RS59193B1 (en) 2010-08-17 2019-10-31 Ambrx Inc Modified relaxin polypeptides and their uses
US9567386B2 (en) 2010-08-17 2017-02-14 Ambrx, Inc. Therapeutic uses of modified relaxin polypeptides
AR083006A1 (en) 2010-09-23 2013-01-23 Lilly Co Eli FORMULATIONS FOR THE STIMULATING FACTOR OF COLONIES OF GRANULOCITS (G-CSF) BOVINE AND VARIANTS OF THE SAME
NZ612320A (en) 2010-12-22 2015-06-26 Baxter Healthcare Sa Materials and methods for conjugating a water soluble fatty acid derivative to a protein
AP2013007046A0 (en) 2011-03-30 2013-08-31 Boehringer Ingelheim Int Anticoagulant antidotes
CN103619877B (en) 2011-04-21 2018-01-02 加文医学研究所 The variable domains molecule and its generation and application method B of modification
CN103702721A (en) 2011-05-31 2014-04-02 诺沃—诺迪斯克有限公司 IL-21 epitope and IL-21 ligands
DK3798230T3 (en) 2011-06-06 2022-10-31 Novo Nordisk As Terapeutiske antistoffer
MX342131B (en) 2011-06-17 2016-09-14 Novo Nordisk As Selective elimination of erosive cells.
AU2012280474A1 (en) 2011-07-01 2014-01-16 Bayer Intellectual Property Gmbh Relaxin fusion polypeptides and uses thereof
PT2717917T (en) 2011-07-05 2016-07-27 Bioasis Technologies Inc P97-antibody conjugates
WO2013011059A1 (en) 2011-07-18 2013-01-24 Novo Nordisk A/S Antagonist antibodies against oscar
WO2013011061A1 (en) 2011-07-18 2013-01-24 Novo Nordisk A/S Antagonistic antibodies against oscar
WO2013011062A2 (en) 2011-07-18 2013-01-24 Novo Nordisk A/S Oscar antagonists
WO2013011063A1 (en) 2011-07-18 2013-01-24 Novo Nordisk A/S Antagonistic antibodies against oscar
EP2793947B1 (en) 2011-12-23 2021-02-03 Innate Pharma Enzymatic conjugation of polypeptides
CN108103069B (en) 2012-02-15 2021-08-10 诺和诺德股份有限公司 Antibodies that bind to and block trigger receptor-1 (TREM-1) expressed by myeloid cells
PL2814842T3 (en) 2012-02-15 2018-12-31 Novo Nordisk A/S Antibodies that bind peptidoglycan recognition protein 1
US9550830B2 (en) 2012-02-15 2017-01-24 Novo Nordisk A/S Antibodies that bind and block triggering receptor expressed on myeloid cells-1 (TREM-1)
EP3967323A3 (en) 2012-06-06 2022-05-04 Bionor Immuno AS Hiv vaccine
CA2875989A1 (en) 2012-06-08 2013-12-12 Sutro Biopharma, Inc. Antibodies comprising site-specific non-natural amino acid residues, methods of their preparation and methods of their use
DK2863955T3 (en) 2012-06-26 2017-01-23 Sutro Biopharma Inc MODIFIED FC PROTEINS, INCLUDING LOCATION-SPECIFIC NON-NATURAL AMINO ACID RESIDUES, CONJUGATES THEREOF, METHODS OF PRODUCING ITS AND PROCEDURES FOR USE THEREOF
WO2014006230A1 (en) 2012-07-06 2014-01-09 Novo Nordisk A/S Il-20 epitopes and il-20 ligands
US10132799B2 (en) 2012-07-13 2018-11-20 Innate Pharma Screening of conjugated antibodies
AU2013296557B2 (en) 2012-07-31 2019-04-18 Bioasis Technologies Inc. Dephosphorylated lysosomal storage disease proteins and methods of use thereof
US20150202287A1 (en) 2012-08-30 2015-07-23 Merrimack Pharmaceuticals, Inc. Combination therapies comprising anti-erbb3 agents
HUE045227T2 (en) 2012-08-31 2019-12-30 Sutro Biopharma Inc Modified amino acids comprising an azido group
EP3564259A3 (en) 2012-11-09 2020-02-12 Innate Pharma Recognition tags for tgase-mediated conjugation
EP2916835A4 (en) 2012-11-12 2016-07-27 Redwood Bioscience Inc Compounds and methods for producing a conjugate
WO2014078733A1 (en) 2012-11-16 2014-05-22 The Regents Of The University Of California Pictet-spengler ligation for protein chemical modification
US9310374B2 (en) 2012-11-16 2016-04-12 Redwood Bioscience, Inc. Hydrazinyl-indole compounds and methods for producing a conjugate
EP2762496A1 (en) 2013-02-05 2014-08-06 EngMab AG Method for the selection of antibodies against BCMA
JP6636803B2 (en) 2013-02-05 2020-01-29 エンクマフ エスアーエールエル Method for selection of antibodies to BCMA
NZ711373A (en) 2013-03-13 2020-07-31 Bioasis Technologies Inc Fragments of p97 and uses thereof
WO2014140300A1 (en) 2013-03-15 2014-09-18 Innate Pharma Solid phase tgase-mediated conjugation of antibodies
US9896513B2 (en) 2013-03-15 2018-02-20 Novo Nordisk A/S Antibodies capable of specifically binding two epitopes on tissue factor pathway inhibitor
EP2789630A1 (en) 2013-04-09 2014-10-15 EngMab AG Bispecific antibodies against CD3e and ROR1
EP3010547B1 (en) 2013-06-20 2021-04-21 Innate Pharma Enzymatic conjugation of polypeptides
EP3010548A1 (en) 2013-06-21 2016-04-27 Innate Pharma Enzymatic conjugation of polypeptides
US9764039B2 (en) 2013-07-10 2017-09-19 Sutro Biopharma, Inc. Antibodies comprising multiple site-specific non-natural amino acid residues, methods of their preparation and methods of their use
WO2015007337A1 (en) 2013-07-19 2015-01-22 Bionor Immuno As Method for the vaccination against hiv
AU2014312190A1 (en) 2013-08-28 2016-02-18 Bioasis Technologies Inc. CNS-targeted conjugates of antibodies
WO2015054658A1 (en) 2013-10-11 2015-04-16 Sutro Biopharma, Inc. Modified amino acids comprising tetrazine functional groups, methods of preparation, and methods of their use
IL293071A (en) 2013-10-15 2022-07-01 Seagen Inc Pegylated drug-linkers for improved ligand-drug conjugate pharmacokinetics
WO2015067755A2 (en) 2013-11-07 2015-05-14 Novo Nordisk A/S Novel methods and antibodies for treating coagulapathy
US9493413B2 (en) 2013-11-27 2016-11-15 Redwood Bioscience, Inc. Hydrazinyl-pyrrolo compounds and methods for producing a conjugate
JOP20200094A1 (en) 2014-01-24 2017-06-16 Dana Farber Cancer Inst Inc Antibody molecules to pd-1 and uses thereof
JOP20200096A1 (en) 2014-01-31 2017-06-16 Children’S Medical Center Corp Antibody molecules to tim-3 and uses thereof
EP3110448B1 (en) 2014-02-26 2020-09-09 The Board of Regents of The University of Texas System Nitrobenzaldehyde proton release for manipulation of cellular acidosis
TWI777174B (en) 2014-03-14 2022-09-11 瑞士商諾華公司 Antibody molecules to lag-3 and uses thereof
WO2015142675A2 (en) 2014-03-15 2015-09-24 Novartis Ag Treatment of cancer using chimeric antigen receptor
KR102472862B1 (en) 2014-03-20 2022-12-05 브리스톨-마이어스 스큅 컴퍼니 Serum albumin-binding fibronectin type iii domains
US10519234B2 (en) 2014-06-27 2019-12-31 Innate Pharma NKp46 binding proteins
WO2015197598A2 (en) 2014-06-27 2015-12-30 Innate Pharma Multispecific antigen binding proteins
TN2017000008A1 (en) 2014-07-17 2018-07-04 Novo Nordisk As Site directed mutagenesis of trem-1 antibodies for decreasing viscosity.
EP3026061A1 (en) 2014-11-26 2016-06-01 Novo Nordisk A/S Site directed mutagenesis of trem-1 antibodies for decreasing viscosity.
EP2975056A1 (en) 2014-07-17 2016-01-20 Novo Nordisk A/S Site directed mutagenesis of TREM-1 antibodies for decreasing viscosity
US9777061B2 (en) 2014-07-21 2017-10-03 Novartis Ag Treatment of cancer using a CD33 chimeric antigen receptor
WO2016014530A1 (en) 2014-07-21 2016-01-28 Novartis Ag Combinations of low, immune enhancing. doses of mtor inhibitors and cars
EP3172237A2 (en) 2014-07-21 2017-05-31 Novartis AG Treatment of cancer using humanized anti-bcma chimeric antigen receptor
WO2016014553A1 (en) 2014-07-21 2016-01-28 Novartis Ag Sortase synthesized chimeric antigen receptors
US20170209492A1 (en) 2014-07-31 2017-07-27 Novartis Ag Subset-optimized chimeric antigen receptor-containing t-cells
JP6919118B2 (en) 2014-08-14 2021-08-18 ノバルティス アーゲー Treatment of cancer with GFRα-4 chimeric antigen receptor
BR112017003104A2 (en) 2014-08-19 2017-12-05 Novartis Ag cancer treatment using an anti-cd123 chimeric antigen receptor
US10577417B2 (en) 2014-09-17 2020-03-03 Novartis Ag Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy
CA2963692A1 (en) 2014-10-09 2016-04-14 Engmab Ag Bispecific antibodies against cd3epsilon and ror1
TWI716362B (en) 2014-10-14 2021-01-21 瑞士商諾華公司 Antibody molecules to pd-l1 and uses thereof
PT3412302T (en) 2014-10-24 2021-06-09 Bristol Myers Squibb Co Modified fgf-21 polypeptides and uses thereof
US20180334490A1 (en) 2014-12-03 2018-11-22 Qilong H. Wu Methods for b cell preconditioning in car therapy
US10610504B2 (en) 2014-12-23 2020-04-07 INSERM (Institut National de la Santé et de la Recherche Médicale) Alpha-cell re-generation combined with conversion to beta cells
IL254817B2 (en) 2015-04-08 2023-12-01 Novartis Ag Cd20 therapies, cd22 therapies, and combination therapies with a cd19 chimeric antigen receptor (car) - expressing cell
EP3286211A1 (en) 2015-04-23 2018-02-28 Novartis AG Treatment of cancer using chimeric antigen receptor and protein kinase a blocker
AU2016284871B2 (en) 2015-06-23 2022-09-29 Innate Pharma Multispecific NK engager proteins
AU2016284866B2 (en) 2015-06-23 2022-09-29 Innate Pharma Multispecific antigen binding proteins
SI3317301T1 (en) 2015-07-29 2021-10-29 Novartis Ag Combination therapies comprising antibody molecules to lag-3
WO2017019897A1 (en) 2015-07-29 2017-02-02 Novartis Ag Combination therapies comprising antibody molecules to tim-3
CN108350073B (en) 2015-08-03 2022-03-18 英格玛布有限责任公司 Monoclonal antibodies against BCMA
JP6893504B2 (en) 2015-09-23 2021-06-23 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ Serum albumin-binding fibronectin type III domain with fast dissociation rate
US11793880B2 (en) 2015-12-04 2023-10-24 Seagen Inc. Conjugates of quaternized tubulysin compounds
AU2016363013B2 (en) 2015-12-04 2022-03-10 Seagen Inc. Conjugates of quaternized tubulysin compounds
KR20180088907A (en) 2015-12-17 2018-08-07 노파르티스 아게 Antibody molecules to PD-1 and uses thereof
RU2018125603A (en) 2015-12-17 2020-01-21 Новартис Аг COMBINATION OF C-MET INHIBITOR WITH ANTIBODY MOLECULE TO PD-1 AND ITS APPLICATIONS
WO2017125897A1 (en) 2016-01-21 2017-07-27 Novartis Ag Multispecific molecules targeting cll-1
KR20180118175A (en) 2016-03-04 2018-10-30 노파르티스 아게 Cells expressing multiple chimeric antigen receptor (CAR) molecules and their uses
EP3432924A1 (en) 2016-03-23 2019-01-30 Novartis AG Cell secreted minibodies and uses thereof
WO2017165851A1 (en) 2016-03-25 2017-09-28 Seattle Genetics, Inc. Process for the preparation of pegylated drug-linkers and intermediates thereof
HRP20230457T1 (en) 2016-04-15 2023-07-21 Novartis Ag Compositions and methods for selective expression of chimeric antigen receptors
KR102419412B1 (en) 2016-05-18 2022-07-12 베링거 인겔하임 인터내셔날 게엠베하 Anti-PD1 and anti-LAG3 antibodies for the treatment of cancer
WO2017203057A1 (en) 2016-05-27 2017-11-30 Alk-Abelló A/S Immunogenic proteins and fragments thereof from allergenic mites
EP3464375A2 (en) 2016-06-02 2019-04-10 Novartis AG Therapeutic regimens for chimeric antigen receptor (car)- expressing cells
WO2018013563A1 (en) 2016-07-12 2018-01-18 Kite Pharma, Inc. Antigen binding molecules and methods of use thereof
CN110461315A (en) 2016-07-15 2019-11-15 诺华股份有限公司 Cytokines release syndrome is treated and prevented using with the Chimeric antigen receptor of kinase inhibitor combination
BR112019001570A2 (en) 2016-07-28 2019-07-09 Novartis Ag chimeric antigen receptor combination therapies and pd-1 inhibitors
BR112019002035A2 (en) 2016-08-01 2019-05-14 Novartis Ag cancer treatment using a chimeric antigen receptor in combination with an inhibitor of a m2 pro-macrophage molecule
US10525083B2 (en) 2016-10-07 2020-01-07 Novartis Ag Nucleic acid molecules encoding chimeric antigen receptors comprising a CD20 binding domain
BR112019008426A2 (en) 2016-11-02 2019-09-03 Engmab Sarl bispecific antibody against bcma and cd3 and an immunological drug for combined use in the treatment of multiple myeloma
US11135307B2 (en) 2016-11-23 2021-10-05 Mersana Therapeutics, Inc. Peptide-containing linkers for antibody-drug conjugates
US11129906B1 (en) 2016-12-07 2021-09-28 David Gordon Bermudes Chimeric protein toxins for expression by therapeutic bacteria
EP3360898A1 (en) 2017-02-14 2018-08-15 Boehringer Ingelheim International GmbH Bispecific anti-tnf-related apoptosis-inducing ligand receptor 2 and anti-cadherin 17 binding molecules for the treatment of cancer
WO2018115262A1 (en) 2016-12-23 2018-06-28 Innate Pharma Heterodimeric antigen binding proteins
US11535662B2 (en) 2017-01-26 2022-12-27 Novartis Ag CD28 compositions and methods for chimeric antigen receptor therapy
CN110637027A (en) 2017-02-08 2019-12-31 百时美施贵宝公司 Modified relaxin polypeptides comprising pharmacokinetic enhancers and uses thereof
US20200048359A1 (en) 2017-02-28 2020-02-13 Novartis Ag Shp inhibitor compositions and uses for chimeric antigen receptor therapy
AU2018237683A1 (en) 2017-03-24 2019-10-31 Seagen Inc. Process for the preparation of glucuronide drug-linkers and intermediates thereof
EP3615055A1 (en) 2017-04-28 2020-03-04 Novartis AG Cells expressing a bcma-targeting chimeric antigen receptor, and combination therapy with a gamma secretase inhibitor
WO2018201051A1 (en) 2017-04-28 2018-11-01 Novartis Ag Bcma-targeting agent, and combination therapy with a gamma secretase inhibitor
US11312783B2 (en) 2017-06-22 2022-04-26 Novartis Ag Antibody molecules to CD73 and uses thereof
WO2019006007A1 (en) 2017-06-27 2019-01-03 Novartis Ag Dosage regimens for anti-tim-3 antibodies and uses thereof
SG11201913137VA (en) 2017-07-11 2020-01-30 Compass Therapeutics Llc Agonist antibodies that bind human cd137 and uses thereof
CN111163798A (en) 2017-07-20 2020-05-15 诺华股份有限公司 Dosing regimens for anti-LAG-3 antibodies and uses thereof
WO2019089753A2 (en) 2017-10-31 2019-05-09 Compass Therapeutics Llc Cd137 antibodies and pd-1 antagonists and uses thereof
WO2019099838A1 (en) 2017-11-16 2019-05-23 Novartis Ag Combination therapies
EP3713961A2 (en) 2017-11-20 2020-09-30 Compass Therapeutics LLC Cd137 antibodies and tumor antigen-targeting antibodies and uses thereof
AU2018371114A1 (en) 2017-11-21 2020-05-07 Innate Pharma Multispecific antigen binding proteins
EP3732254A4 (en) 2017-12-26 2021-12-22 Becton, Dickinson and Company Deep ultraviolet-excitable water-solvated polymeric dyes
US20210038659A1 (en) 2018-01-31 2021-02-11 Novartis Ag Combination therapy using a chimeric antigen receptor
US10844228B2 (en) 2018-03-30 2020-11-24 Becton, Dickinson And Company Water-soluble polymeric dyes having pendant chromophores
JOP20200240A1 (en) 2018-04-02 2020-09-27 Bristol Myers Squibb Co Anti-trem-1 antibodies and uses thereof reference to sequence listing submitted electronically via efs-web
US20210147547A1 (en) 2018-04-13 2021-05-20 Novartis Ag Dosage Regimens For Anti-Pd-L1 Antibodies And Uses Thereof
WO2019210153A1 (en) 2018-04-27 2019-10-31 Novartis Ag Car t cell therapies with enhanced efficacy
EP3569618A1 (en) 2018-05-19 2019-11-20 Boehringer Ingelheim International GmbH Antagonizing cd73 antibody
WO2019226658A1 (en) 2018-05-21 2019-11-28 Compass Therapeutics Llc Multispecific antigen-binding compositions and methods of use
US20200109195A1 (en) 2018-05-21 2020-04-09 Compass Therapeutics Llc Compositions and methods for enhancing the killing of target cells by nk cells
WO2019227003A1 (en) 2018-05-25 2019-11-28 Novartis Ag Combination therapy with chimeric antigen receptor (car) therapies
US20210214459A1 (en) 2018-05-31 2021-07-15 Novartis Ag Antibody molecules to cd73 and uses thereof
SG11202011830SA (en) 2018-06-13 2020-12-30 Novartis Ag Bcma chimeric antigen receptors and uses thereof
US20210238268A1 (en) 2018-06-19 2021-08-05 Atarga, Llc Antibody molecules to complement component 5 and uses thereof
AR116109A1 (en) 2018-07-10 2021-03-31 Novartis Ag DERIVATIVES OF 3- (5-AMINO-1-OXOISOINDOLIN-2-IL) PIPERIDINE-2,6-DIONA AND USES OF THE SAME
CA3107332A1 (en) 2018-07-22 2020-01-30 Bioasis Technologies Inc. Treatment of lymphatic metastases
WO2020021465A1 (en) 2018-07-25 2020-01-30 Advanced Accelerator Applications (Italy) S.R.L. Method of treatment of neuroendocrine tumors
SG11202102427XA (en) 2018-09-11 2021-04-29 Ambrx Inc Interleukin-2 polypeptide conjugates and their uses
EP3867265A1 (en) 2018-10-19 2021-08-25 Ambrx, Inc. Interleukin-10 polypeptide conjugates, dimers thereof, and their uses
GB201818477D0 (en) 2018-11-13 2018-12-26 Emstopa Ltd Tissue plasminogen activator antibodies and method of use thereof
BR112021008795A2 (en) 2018-11-13 2021-08-31 Compass Therapeutics Llc MULTISPECIFIC BINDING CONSTRUCTS AGAINST CHECKPOINT MOLECULES AND THEIR USES
CN113195539A (en) 2018-12-20 2021-07-30 诺华股份有限公司 Pharmaceutical combination
EP3897637A1 (en) 2018-12-20 2021-10-27 Novartis AG Dosing regimen and pharmaceutical combination comprising 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives
WO2020168017A1 (en) 2019-02-12 2020-08-20 Ambrx, Inc. Compositions containing, methods and uses of antibody-tlr agonist conjugates
CA3123519A1 (en) 2019-02-15 2020-08-20 Novartis Ag Substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
WO2020165833A1 (en) 2019-02-15 2020-08-20 Novartis Ag 3-(1-oxo-5-(piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
US10871640B2 (en) 2019-02-15 2020-12-22 Perkinelmer Cellular Technologies Germany Gmbh Methods and systems for automated imaging of three-dimensional objects
WO2020172553A1 (en) 2019-02-22 2020-08-27 Novartis Ag Combination therapies of egfrviii chimeric antigen receptors and pd-1 inhibitors
SG11202110732XA (en) 2019-03-29 2021-10-28 Atarga Llc Anti fgf23 antibody
MA55504A (en) 2019-04-01 2022-02-09 Novo Nordisk As ANTIBODIES AGAINST LIRAGLUTIDE AND THEIR USE
CN114174536A (en) 2019-07-15 2022-03-11 百时美施贵宝公司 anti-TREM-1 antibodies and uses thereof
CN114144435A (en) 2019-07-15 2022-03-04 百时美施贵宝公司 Antibodies against human TREM-1 and uses thereof
US20230049954A1 (en) * 2019-09-06 2023-02-16 The Regents Of The University Of California Chimeric antigen receptors and related methods and compositions for the treatment of cancer
JP2022553293A (en) 2019-10-21 2022-12-22 ノバルティス アーゲー Combination therapy with venetoclax and a TIM-3 inhibitor
CA3157665A1 (en) 2019-10-21 2021-04-29 Novartis Ag Tim-3 inhibitors and uses thereof
BR112022010206A2 (en) 2019-11-26 2022-11-29 Novartis Ag CHIMERIC ANTIGEN RECEPTORS AND USES THEREOF
JP2023507190A (en) 2019-12-20 2023-02-21 ノバルティス アーゲー Use of anti-TGFβ antibodies and checkpoint inhibitors to treat proliferative diseases
CN113186185B (en) * 2020-01-14 2023-05-26 东北林业大学 Method for efficiently enriching host DNA from mammal feces
US20210222244A1 (en) 2020-01-17 2021-07-22 Becton, Dickinson And Company Methods and compositions for single cell secretomics
IL293752A (en) 2020-01-17 2022-08-01 Novartis Ag Combination comprising a tim-3 inhibitor and a hypomethylating agent for use in treating myelodysplastic syndrome or chronic myelomonocytic leukemia
BR112022016633A2 (en) 2020-02-27 2022-12-13 Novartis Ag METHODS FOR PRODUCING CELLS THAT EXPRESS CHIMERIC ANTIGEN RECEPTOR
WO2021183832A1 (en) 2020-03-11 2021-09-16 Ambrx, Inc. Interleukin-2 polypeptide conjugates and methods of use thereof
US20210355468A1 (en) 2020-05-18 2021-11-18 Bioasis Technologies, Inc. Compositions and methods for treating lewy body dementia
JP2023504675A (en) 2020-05-19 2023-02-06 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Binding molecules for cancer treatment
EP4157455A1 (en) 2020-05-29 2023-04-05 Universität zu Köln Neutralizing antibodies against sars-related coronavirus
US20210393787A1 (en) 2020-06-17 2021-12-23 Bioasis Technologies, Inc. Compositions and methods for treating frontotemporal dementia
AU2021297099A1 (en) 2020-06-23 2023-01-05 Novartis Ag Dosing regimen comprising 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives
CR20230009A (en) 2020-07-16 2023-01-25 Novartis Ag Anti-betacellulin antibodies, fragments thereof, and multi-specific binding molecules
WO2022026592A2 (en) 2020-07-28 2022-02-03 Celltas Bio, Inc. Antibody molecules to coronavirus and uses thereof
EP4188549A1 (en) 2020-08-03 2023-06-07 Novartis AG Heteroaryl substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
WO2022033975A1 (en) 2020-08-10 2022-02-17 Innate Pharma Cell surface mica and micb detection using antibodies
EP4199968A1 (en) 2020-08-20 2023-06-28 Ambrx, Inc. Antibody-tlr agonist conjugates, methods and uses thereof
EP4204021A1 (en) 2020-08-31 2023-07-05 Advanced Accelerator Applications International S.A. Method of treating psma-expressing cancers
WO2022043558A1 (en) 2020-08-31 2022-03-03 Advanced Accelerator Applications International Sa Method of treating psma-expressing cancers
EP4232474A1 (en) 2020-10-21 2023-08-30 Boehringer Ingelheim International GmbH Bispecific anti-vegf and anti-trkb binding molecules for the treatment of eye diseases
CA3199319A1 (en) 2020-10-22 2022-04-28 Janssen Biotech, Inc. Proteins comprising delta-like ligand 3 (dll3) antigen binding domains and their uses
EP4240765A2 (en) 2020-11-06 2023-09-13 Novartis AG Antibody fc variants
US20240033358A1 (en) 2020-11-13 2024-02-01 Novartis Ag Combination therapies with chimeric antigen receptor (car)-expressing cells
EP4284510A1 (en) 2021-01-29 2023-12-06 Novartis AG Dosage regimes for anti-cd73 and anti-entpd2 antibodies and uses thereof
WO2022182872A2 (en) 2021-02-24 2022-09-01 Alladapt Immunotherapeutics, Inc. Compositions and methods for identification of cross-reactive allergenic proteins and treatment of allergies
KR20230162793A (en) 2021-03-26 2023-11-28 얀센 바이오테크 인코포레이티드 Humanized antibodies against paired helical filament tau and uses thereof
CA3207652A1 (en) 2021-03-26 2022-09-29 Stephanie Cornen Cytokine anchors for nkp46-binding nk cell engager proteins
CA3213805A1 (en) 2021-04-03 2022-10-06 Feng Tian Anti-her2 antibody-drug conjugates and uses thereof
WO2022214432A1 (en) 2021-04-05 2022-10-13 Innate Pharma Immunohistochemistry methods and kir3dl2-specific reagents
TW202304979A (en) 2021-04-07 2023-02-01 瑞士商諾華公司 USES OF ANTI-TGFβ ANTIBODIES AND OTHER THERAPEUTIC AGENTS FOR THE TREATMENT OF PROLIFERATIVE DISEASES
AR125874A1 (en) 2021-05-18 2023-08-23 Novartis Ag COMBINATION THERAPIES
EP4095156A1 (en) 2021-05-28 2022-11-30 Universität zu Köln Neutralizing antibodies against hepatitis c virus
EP4352098A1 (en) 2021-06-09 2024-04-17 Innate Pharma Multispecific proteins binding to nkp46, a cytokine receptor, a tumour antigen and cd16a
WO2022258691A1 (en) 2021-06-09 2022-12-15 Innate Pharma Multispecific proteins binding to nkg2d, a cytokine receptor, a tumour antigen and cd16a
CA3227227A1 (en) 2021-06-09 2022-12-15 Laurent Gauthier Multispecific antibodies binding to cd20, nkp46, cd16 and conjugated to il-2
WO2022258678A1 (en) 2021-06-09 2022-12-15 Innate Pharma Multispecific proteins binding to nkp30, a cytokine receptor, a tumour antigen and cd16a
TW202317625A (en) 2021-06-17 2023-05-01 德商百靈佳殷格翰國際股份有限公司 Novel tri-specific binding molecules
WO2023044483A2 (en) 2021-09-20 2023-03-23 Voyager Therapeutics, Inc. Compositions and methods for the treatment of her2 positive cancer
EP4155349A1 (en) 2021-09-24 2023-03-29 Becton, Dickinson and Company Water-soluble yellow green absorbing dyes
WO2023092004A1 (en) 2021-11-17 2023-05-25 Voyager Therapeutics, Inc. Compositions and methods for the treatment of tau-related disorders
EP4190810A1 (en) 2021-12-01 2023-06-07 Universität zu Köln Neutralizing antibodies against sars-related coronavirus
WO2023099688A1 (en) 2021-12-01 2023-06-08 Universität Zu Köln Neutralizing antibodies against sars-related coronavirus
US20230383010A1 (en) 2022-02-07 2023-11-30 Visterra, Inc. Anti-idiotype antibody molecules and uses thereof
WO2023170291A1 (en) 2022-03-11 2023-09-14 Janssen Pharmaceutica Nv Multispecific antibodies and uses thereof
TW202346355A (en) 2022-03-11 2023-12-01 比利時商健生藥品公司 Multispecific antibodies and uses thereof
WO2023170295A1 (en) 2022-03-11 2023-09-14 Janssen Pharmaceutica Nv Multispecific antibodies and uses thereof
WO2023220695A2 (en) 2022-05-13 2023-11-16 Voyager Therapeutics, Inc. Compositions and methods for the treatment of her2 positive cancer
WO2024007016A2 (en) 2022-07-01 2024-01-04 Beckman Coulter, Inc. Novel fluorescent dyes and polymers from dihydrophenanthrene derivatives
WO2024013315A1 (en) 2022-07-15 2024-01-18 Boehringer Ingelheim International Gmbh Binding molecules for the treatment of cancer
WO2024030976A2 (en) 2022-08-03 2024-02-08 Voyager Therapeutics, Inc. Compositions and methods for crossing the blood brain barrier
WO2024044327A1 (en) 2022-08-26 2024-02-29 Beckman Coulter, Inc. Dhnt monomers and polymer dyes with modified photophysical properties
WO2024056861A1 (en) 2022-09-15 2024-03-21 Avidicure Ip B.V. Multispecific antigen binding proteins for stimulating nk cells and use thereof

Family Cites Families (58)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4179337A (en) 1973-07-20 1979-12-18 Davis Frank F Non-immunogenic polypeptides
US5049504A (en) 1986-11-24 1991-09-17 Genex Corporation Bioadhesive coding sequences
US5202256A (en) 1984-09-13 1993-04-13 Enzon Labs, Inc. Bioadhesive precursor protein expression vectors
US5202236A (en) 1984-09-13 1993-04-13 Enzon Labs Inc. Method of producing bioadhesive protein
US5260203A (en) * 1986-09-02 1993-11-09 Enzon, Inc. Single polypeptide chain binding molecules
US5869620A (en) 1986-09-02 1999-02-09 Enzon, Inc. Multivalent antigen-binding proteins
US4704692A (en) 1986-09-02 1987-11-03 Ladner Robert C Computer based system and method for determining and displaying possible chemical structures for converting double- or multiple-chain polypeptides to single-chain polypeptides
US4946778A (en) * 1987-09-21 1990-08-07 Genex Corporation Single polypeptide chain binding molecules
US4881175A (en) 1986-09-02 1989-11-14 Genex Corporation Computer based system and method for determining and displaying possible chemical structures for converting double- or multiple-chain polypeptides to single-chain polypeptides
US5166320A (en) 1987-04-22 1992-11-24 University Of Connecticut Carrier system and method for the introduction of genes into mammalian cells
US5258498A (en) 1987-05-21 1993-11-02 Creative Biomolecules, Inc. Polypeptide linkers for production of biosynthetic proteins
US5091513A (en) 1987-05-21 1992-02-25 Creative Biomolecules, Inc. Biosynthetic antibody binding sites
US4904582A (en) 1987-06-11 1990-02-27 Synthetic Genetics Novel amphiphilic nucleic acid conjugates
US5122614A (en) 1989-04-19 1992-06-16 Enzon, Inc. Active carbonates of polyalkylene oxides for modification of polypeptides
US5358932A (en) * 1989-12-29 1994-10-25 Zymogenetics, Inc. Hybrid protein C
GB9012995D0 (en) * 1990-06-11 1990-08-01 Celltech Ltd Multivalent antigen-binding proteins
US5766897A (en) * 1990-06-21 1998-06-16 Incyte Pharmaceuticals, Inc. Cysteine-pegylated proteins
JPH06506217A (en) 1991-03-18 1994-07-14 エンゾン，インコーポレーテッド Hydrazine-containing conjugates of polypeptides or glycopolypeptides and polymers
US5212075A (en) 1991-04-15 1993-05-18 The Regents Of The University Of California Compositions and methods for introducing effectors to pathogens and cells
US5872222A (en) 1991-04-19 1999-02-16 Tanox Biosystems, Inc. Conjugates of polymers and antibodies specific for T lymphocytes, and their use as adjuvants
US6787153B1 (en) * 1991-06-28 2004-09-07 Mitsubishi Chemical Corporation Human monoclonal antibody specifically binding to surface antigen of cancer cell membrane
US5521291A (en) 1991-09-30 1996-05-28 Boehringer Ingelheim International, Gmbh Conjugates for introducing nucleic acid into higher eucaryotic cells
US5981273A (en) 1991-09-30 1999-11-09 Boehringer Ingelheim Int'l. Gmbh Composition comprising an endosomolytic agent for introducing nucleic acid complexes into higher eucaryotic cells
NZ244306A (en) 1991-09-30 1995-07-26 Boehringer Ingelheim Int Composition for introducing nucleic acid complexes into eucaryotic cells, complex containing nucleic acid and endosomolytic agent, peptide with endosomolytic domain and nucleic acid binding domain and preparation
JPH07501451A (en) 1991-11-25 1995-02-16 エンゾン・インコーポレイテッド Multivalent antigen binding protein
US6025165A (en) 1991-11-25 2000-02-15 Enzon, Inc. Methods for producing multivalent antigen-binding proteins
EP1997894B1 (en) 1992-02-06 2011-03-30 Novartis Vaccines and Diagnostics, Inc. Biosynthetic binding protein for cancer marker
US5714350A (en) 1992-03-09 1998-02-03 Protein Design Labs, Inc. Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region
US6113946A (en) 1992-04-03 2000-09-05 The Regents Of The University Of California Self-assembling polynucleotide delivery system comprising dendrimer polycations
US6329507B1 (en) 1992-08-21 2001-12-11 The Dow Chemical Company Dimer and multimer forms of single chain polypeptides
WO1994012520A1 (en) 1992-11-20 1994-06-09 Enzon, Inc. Linker for linked fusion polypeptides
US5359030A (en) * 1993-05-10 1994-10-25 Protein Delivery, Inc. Conjugation-stabilized polypeptide compositions, therapeutic delivery and diagnostic formulations comprising same, and method of making and using the same
US5880131A (en) 1993-10-20 1999-03-09 Enzon, Inc. High molecular weight polymer-based prodrugs
AU8052194A (en) 1993-10-20 1995-05-08 Enzon, Inc. 2'- and/or 7- substituted taxoids
US5443953A (en) 1993-12-08 1995-08-22 Immunomedics, Inc. Preparation and use of immunoconjugates
US5844107A (en) 1994-03-23 1998-12-01 Case Western Reserve University Compacted nucleic acids and their delivery to cells
US5656465A (en) 1994-05-04 1997-08-12 Therion Biologics Corporation Methods of in vivo gene delivery
US5730990A (en) * 1994-06-24 1998-03-24 Enzon, Inc. Non-antigenic amine derived polymers and polymer conjugates
US5888773A (en) * 1994-08-17 1999-03-30 The United States Of America As Represented By The Department Of Health And Human Services Method of producing single-chain Fv molecules
US5670132A (en) 1994-09-20 1997-09-23 Immunomedics, Inc. Modified radioantibody fragments for reduced renal uptake
US5763733A (en) * 1994-10-13 1998-06-09 Enzon, Inc. Antigen-binding fusion proteins
ATE202145T1 (en) 1994-11-01 2001-06-15 Winfried Wels NUCLEIC ACID DELIVERY SYSTEM
WO1996040731A1 (en) 1995-06-07 1996-12-19 Mount Sinai School Of Medicine Of The City University Of New York Pegylated modified proteins
CA2232834A1 (en) 1995-09-21 1997-03-27 University Of Utah Targeting of conjugates of poly(ethylene glycol) and antibodies against glutamic acid decarboxylase to islet cells
CN1173878A (en) 1995-10-16 1998-02-18 尤尼利弗公司 Bifunctional or bivalent antibody fragment analogue
US6090382A (en) * 1996-02-09 2000-07-18 Basf Aktiengesellschaft Human antibodies that bind human TNFα
TR199801532T2 (en) * 1996-02-09 1998-11-23 Basf Aktiengesellschaft Human antibodies that bind human TNFalpha.
GB9625640D0 (en) 1996-12-10 1997-01-29 Celltech Therapeutics Ltd Biological products
US6117980A (en) 1997-02-21 2000-09-12 Genentech, Inc. Humanized anti-IL-8 monoclonal antibodies
US6025158A (en) 1997-02-21 2000-02-15 Genentech, Inc. Nucleic acids encoding humanized anti-IL-8 monoclonal antibodies
EP0968291B1 (en) 1997-02-21 2004-01-28 Genentech, Inc. Antibody fragment-polymer conjugates
US5830698A (en) * 1997-03-14 1998-11-03 Idec Pharmaceuticals Corporation Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same
JP2002505574A (en) * 1997-04-30 2002-02-19 エンゾン，インコーポレイテッド Polyalkylene oxide-modified single-chain polypeptides
GB9812545D0 (en) 1998-06-10 1998-08-05 Celltech Therapeutics Ltd Biological products
US6333396B1 (en) * 1998-10-20 2001-12-25 Enzon, Inc. Method for targeted delivery of nucleic acids
US6908963B2 (en) * 2001-10-09 2005-06-21 Nektar Therapeutics Al, Corporation Thioester polymer derivatives and method of modifying the N-terminus of a polypeptide therewith
RU2004117915A (en) * 2001-11-12 2005-05-10 Мерк Патент ГмбХ (DE) MODIFIED ANTI-TNF ALPHA ANTIBODY
US7101978B2 (en) * 2003-01-08 2006-09-05 Applied Molecular Evolution TNF-α binding molecules

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