Targeted therapeutics based on engineered proteins for tyrosine kinases receptors, including igf-ir

Patent metadata

Field	Value
Publication number	US-2017190761-A1
Application number	US-201715404749-A
Country	US
Kind code	A1
Filing date	Jan 12, 2017
Priority date	Nov 22, 2006
Publication date	Jul 6, 2017
Grant date	—

Abstract

The present invention provides innovative proteins that bind to insulin-like growth factor-I receptor (IGF-IR), as well as other important proteins. The invention also provides innovative proteins in pharmaceutical preparations and derivatives of such proteins and the uses of same in diagnostic, research and therapeutic applications. The invention further provides cells comprising such proteins, polynucleotide encoding such proteins or fragments thereof, and vectors comprising the polynucleotides encoding the innovative proteins.

First claim

1 - 15 . (canceled)

16 . A nucleic acid encoding a tenth fibronectin type III ( 10 Fn3) domain comprising an amino acid sequence that is at least 85% identical to any one of SEQ ID NOs: 184-203, wherein the 10 Fn3 domain binds human insulin-like growth factor-I receptor (IGF-IR) with a dissociation constant of about 1 μM or less.

17 . The nucleic acid of claim 16 , wherein the 10 Fn3 domain comprises an amino acid sequence that is at least 90% identical to any one of SEQ ID NOs: 184-203.

18 . The nucleic acid of claim 17 , wherein the 10 Fn3 domain comprises an amino acid sequence of any one of SEQ ID NOs: 184-203.

19 . A nucleic acid encoding a encoding a tenth fibronectin type III ( 10 Fn3) domain consisting of an amino acid sequence that is at least 85% identical to any one of SEQ ID NOs: 184-203, wherein the 10 Fn3 domain binds human insulin-like growth factor-I receptor (IGF-IR) with a dissociation constant of about 1 μM or less.

20 . The nucleic acid of claim 19 , wherein the amino acid sequence of the 10 Fn3 domain is at least 90% identical to any one of SEQ ID NOs: 184-203.

21 . The nucleic acid of claim 20 , wherein the amino acid sequence of the 10 Fn3 domain is identical to any one of SEQ ID NOs: 184-203.

22 . A vector comprising the nucleic acid of claim 16 .

23 . A vector comprising the nucleic acid of claim 19 .

24 . A host cell expressing the nucleic acid of claim 16 .

25 . A host cell expressing the nucleic acid of claim 19 .

26 . A method of treating a subject have cancer associated with increased insulin-like growth factor activity, the method comprising administering to a subject in need thereof a pharmaceutically effective amount of a polypeptide comprising an altered tenth fibronectin type III ( 10 Fn3) domain comprising an amino acid sequence that is at least 80% identical to any one of SEQ ID NOs: 184-203, and wherein the 10 Fn3 domain binds human insulin-like growth factor-I receptor (IGF-IR) with a dissociation constant of about 1 μM or less.

27 . The method of claim 26 , wherein the altered 10 Fn3 domain binds human IGF-IR with a disassociation constant of about 10 nM or less.

28 . The method of claim 26 , wherein the altered 10 Fn3 domain comprises an amino acid sequence that is at least 85% identical to any one of SEQ ID NOs: 184-203.

29 . The method of claim 26 , wherein the altered 10 Fn3 domain comprises an amino acid sequence that is at least 90% identical to any one of SEQ ID NOs: 184-203.

30 . The method of claim 26 , wherein the altered 10 Fn3 domain comprises an amino acid sequence that is at least 95% identical to any one of SEQ ID NOs: 184-203.

31 . The method of claim 26 , wherein the altered 10 Fn3 domain comprises an amino acid sequence that is identical to any one of SEQ ID NOs: 184-203.

32 . The method of claim 26 , wherein the altered 10 Fn3 domain comprises an amino acid sequence of SEQ ID NO: 184.

33 . The method of claim 26 , wherein the polypeptide further comprises one or more pharmacokinetic (PK) moieties selected from: a polyoxyalkylene moiety, a human serum albumin binding protein, sialic acid, human serum albumin, transferrin, and an Fc fragment.

34 . The method of claim 33 , wherein the PK moiety is the polyoxyalkylene moiety and said polyoxyalkylene moiety is polyethylene glycol.

35 . The method of claim 26 , wherein the cancer is selected from the group consisting of breast cancer, colon cancer, ovarian carcinoma, osteosarcoma, cervical cancer, prostate cancer lung cancer, synovial carcinoma, pancreatic cancer, plasmacytoma, rhabdomyosarcoma and multiple myeloma.

Assignees

• Bristol Myers Squibb Co

Inventors

• Camphausen Ray
• Fabrizio David
• Wright Martin C
• Gage Patrick
• Mendlein John

Classifications

• A61K47/644

  Transferrin, e.g. a lactoferrin or ovotransferrin · CPC title

• C07K14/78 Primary

  Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG] · CPC title

• C07K16/00

  Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies · CPC title

• A61K38/18

  Growth factors; Growth regulators · CPC title

• C07K2319/74

  containing a fusion for binding to a cell surface receptor · CPC title