Hemoglobin mutants with increased soluble expression and/or reduced nitric ...

(12) United States Patent

Weickert et al.

US006455676B1

(io) Patent No.: US 6,455,676 Bl (45) Date of Patent: Sep. 24,2002

(60)

(51) (52) (58)

(56)

WO

wo wo

PCT Pub. Date: Nov. 12, 1998

Related U.S. Application Data

Provisional application No. 60/057,986, filed on Sep. 5, 1997, and provisional application No. 60/045,364, filed on May 2, 1997.

Int. CI. C07K 14/805

U.S. CI 530/385

Field of Search 530/385

References Cited
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(List continued on next page.)

Primary Examiner—Karen Cochrane Carlson

(74) Attorney, Agent, or Firm—Senniger, Powers, Leavitt

& Roedel

Moore, E., et al., "Cooperativity in the Dissociation of Nitric Oxide from Hemoglobin*," 1976 (Journal of Biological Chemistry, vol. 251, pp. 2788-2794.

The invention relates to novel recombinant hemoglobins having reduced nitric oxide scavenging and/or increased high soluble expression. The invention further relates to methods of increasing the soluble expression of recombinant hemoglobin by adding exogenous hemin in molar excess of the heme binding sites of recombinant hemoglobin.

12 Claims, 13 Drawing Sheets

OTHER PUBLICATIONS

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