Granted Patent B2

US 10,245,307 · App. 15/175,644 · Granted Apr 2, 2019

Inventors: Robert Charles Ladner (Ijamsville, MD); Arthur Charles Ley (Newton, MA); Shirish Hirani (Arlington, MA); Anthony Williams (Melrose, MA)

Assignee: Dyax Corp.

A61K38/57A61K9/0019A61K38/55C12N9/6445

Abstract

Claims (35)

1. A method for inhibiting plasma kallikrein in a patient in need thereof comprising,

administering to the patient a composition comprising a pharmaceutically acceptable carrier and a polypeptide comprising the amino acid sequence: Xaa1 Xaa2 Xaa3 Xaa4 Cys Xaa6 Xaa7Xaa8 Xaa9 Xaa10 Xaa11 Gly Xaa13 Cys Xaa15 Xaa16 Xaa17 Xaa18 Xaa19 Xaa20 Xaa21 Xaa22Xaa23 Xaa24 Xaa25 Xaa26 Xaa27 Xaa28 Xaa29 Cys Xaa31 Xaa32 Phe Xaa34 Xaa35 Gly Gly Cys Xaa39 Xaa40 Xaa41 Xaa42 Xaa43 Xaa44 Xaa45 Xaa46 Xaa47 Xaa48 Xaa49 Xaa50 Cys Xaa52Xaa53 Xaa54 Cys Xaa56 Xaa57 Xaa58 (SEQ ID NO:1), wherein

Xaa1, Xaa2, Xaa3, Xaa4, Xaa56, Xaa57 or Xaa58 are each individually an amino acid or absent;

Xaa6, Xaa7, Xaa8, Xaa9, Xaa20, Xaa24, Xaa25, Xaa26, Xaa27, Xaa28, Xaa29, Xaa41, Xaa42, Xaa44, Xaa46, Xaa47, Xaa48, Xaa49, Xaa50, Xaa52, Xaa53, and Xaa54 are each any amino acid;

Xaa10 is Asp;

Xaa11 is an amino acid selected from the group consisting of: Asp, Gly, Ser, Val, Asn, Ile, Ala and Thr;

Xaa13 is an amino acid selected from the group consisting of: Arg, His, Pro, Asn, Ser, Thr, Ala, Gly, Lys and Gln;

Xaa15 is an amino acid selected from the group consisting of: Arg, Lys, Ala, Ser, Gly, Met, Asn and Gln;

Xaa16 is an amino acid selected from the group consisting of: Ala, Gly, Ser, Asp and Asn;

Xaa17 is an amino acid selected from the group consisting of: Ala, Asn, Ser, Ile, Gly, Val, Gln and Thr;

Xaa18 is an amino acid selected from the group consisting of: His, Leu, Gln and Ala;

Xaa19 is an amino acid selected from the group consisting of: Pro, Gln, Leu, Asn and Ile;

Xaa21 is an amino acid selected from the group consisting of: Trp, Phe, Tyr, His and Ile;

Xaa22 is an amino acid selected from the group consisting of: Tyr and Phe;

Xaa23 is an amino acid selected from the group consisting of: Tyr and Phe;

Xaa31 is an amino acid selected from the group consisting of: Glu, Asp, Gln, Asn, Ser, Ala, Val, Leu, Ile and Thr;

Xaa32 is an amino acid selected from the group consisting of: Glu, Gln, Asp Asn, Pro, Thr, Leu, Ser, Ala, Gly and Val;

Xaa34 is an amino acid selected from the group consisting of: Ile, Asn, and Leu;

Xaa35 is an amino acid selected from the group consisting of: Tyr, Trp and Phe;

Xaa39 is an amino acid selected from the group consisting of: Glu, Gly, Ala, Ser and Asp;

Xaa40 is an amino acid selected from the group consisting of: Gly and Ala;

Xaa43 is an amino acid selected from the group consisting of: Asn and Gly;

Xaa45 is an amino acid selected from the group consisting of: Phe and Tyr;

and wherein the polypeptide inhibits kallikrein.

2. The method of claim 1 , wherein Xaa11 is Asp, Xaa21 is Trp, Xaa31is Glu, Xaa32 is Glu, Xaa34 is Ile, Xaa35 is Tyr, and/or Xaa39 is Glu.

3. The method of claim 1 , wherein Xaa13 is Pro, Xaa15 is Arg, Xaa16 is Ala, Xaa17is Ala, Xaa18 is His and Xaa19 is Pro.

4. A method for inhibiting plasma kallikrein in a patient in need thereof, comprising administering to the patient in need thereof a composition comprising a polypeptide consisting of the amino acid sequence: Glu Ala Met His Ser Phe Cys Ala Phe Lys Ala Asp Asp Gly Pro Cys Arg Ala Ala His Pro Arg Trp Phe Phe Asn Ile Phe Thr Arg Gln Cys Glu Glu Phe Ile Tyr Gly Gly Cys Glu Gly Asn Gln Asn Arg Phe Glu Ser Leu Glu Glu Cys Lys Lys Met Cys Thr Arg Asp (SEQ ID NO:2), wherein the polypeptide inhibits kallikrein.

5. The method of claim 1 , wherein the administering is performed intravenously, parenterally, or subcutaneously.

6. The method of claim 1 , wherein Xaa21 is Trp.

7. The method of claim 1 , wherein Xaa31 is Glu.

8. The method of claim 1 , wherein Xaa32 is Glu.

9. The method of claim 1 , wherein Xaa34 is Ile.

10. The method of claim 1 , wherein Xaa35 is Tyr.

11. The method of claim 1 , wherein Xaa39 is Glu.

12. The method of claim 4 , wherein the administering is performed intravenously, parenterally, or subcutaneously.

Assignments (2)

Continuity (9)