Human antibodies specific to kdr and uses thereof

US 20050234225A1
Filed: 03/04/2003
Published: 10/20/2005
Est. Priority Date: 03/04/2002
Status: Active Grant

First Claim

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1. An isolated human antibody or fragment thereof which binds selectively to KDR.

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Abstract

The invention provides an antibodies that bind to KDR with an affinity comparable to or higher than human VEGF, and that neutralizes activation of KDR. Antibodies include whole immunoglobulins, monovalent Fabs and single chain antibodies, multivalent single chain antibodies, diabodies, triabodies, and single domain antibodies. The invention further provides nucleic acids and host cells that encode and express these antibodies. The invention further provides a method of neutralizing the activation of KDR, a method of inhibiting angiogenesis in a mammal and a method of inhibiting tumor growth in a mammal.

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30 Claims

1. An isolated human antibody or fragment thereof which binds selectively to KDR.
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30)
- - 2. The antibody of claim 1, wherein the fragment is selected from the group consisting of a single chain antibody, a Fab, a single chain Fv, a diabody, and a triabody.
  - 3. The antibody of claim 1, wherein the antibody or fragment thereof inhibits binding of VEGF to KDR.
  - 4. The antibody of claim 1, wherein the antibody comprises complementarity determining regions represented by SEQ ID NO:
    - 1 at CDRL1;
      
      SEQ ID NO;
      
      2 at CDRL2;
      
      SEQ ID NO;
      
      3 at CDRL3;
      
      SEQ ID NO;
      
      13 at CDRH1;
      
      SEQ ID NO;
      
      14 at CDRH2; and
      
      SEQ ID NO;
      
      15 at CDRH3.
  - 5. The antobody of claim 1, wherein the antibody comprises a light chain variable domain represented by SEQ ID NO:
    - 26 and a heavy chain variable doamin represented by SEQ ID NO;
      
      24.
  - 6. The antibody of claim 1, wherein the antibody comprises complementarity determining regions represented by SEQ ID NO:
    - 81 at CDRL1;
      
      SEQ ID NO;
      
      82 at CDRL2;
      
      SEQ ID NO;
      
      83 at CDRL3;
      
      SEQ ID NO;
      
      13 at CDRH1;
      
      SEQ ID NO;
      
      14 at CDRH2; and
      
      SEQ ID NO;
      
      15 at CDRH3.
  - 7. The antibody of claim 1, wherein the antibody comprises a light chain variable domain respresented by SEQ ID NO:
    - 53 and a heavy chain variable domain represented by SEQ ID NO;
      
      24.
  - 8. The antibody of claim 1, wherein the antibody comprises a heavy chain variable domain selected from the group consisting of SEQ ID NO:
    - 20, SEQ ID NO;
      
      24, SEQ ID NO;
      
      31.
  - 9. The antibody of claim 1, wherein the antibody comprises a light chain variable domain selected from the group consisting of SEQ ID NO:
    - 22, SEQ ID NO;
      
      26, SEQ ID NO;
      
      29, SEQ ID NO;
      
      33, SEQ ID NO;
      
      35, SEQ ID NO;
      
      37, SEQ ID NO;
      
      39, SEQ ID NO;
      
      41, SEQ ID NO;
      
      43, SEQ ID NO;
      
      45, SEQ ID NO;
      
      47, SEQ ID NO;
      
      49, SEQ ID NO;
      
      51, and SEQ ID NO;
      
      53.
  - 18. A method of neutralizing activation of KDR comprising administering an effective amount of an antibody of claim 1.
  - 19. A method of inhibiting angiogenesis comprising adminstering an effective amount of an antibody of claim 1.
  - 20. A method of reducing tumor growth comprising adminstering an effective amount of an antibody of claim 1.
  - 21. The method of claim 19, wherein the antibody neutralizes KDR.
  - 22. The method of claim 20, wherein the tumor overexpresses KDR.
  - 23. The method of claim 20, wherein the tumor is a tumor of the colon.
  - 24. The method of claim 20, wherein the tumor is a breast tumor.
  - 25. The method of claim 20, wherein the tumor is a non-solid tumor.
  - 26. The method of claim 20, which further comprises administering of a therapeutically effective amount of an epidermal growth factor receptor (EGFR) antagonist.
  - 27. The method of claim 20, which further comprises administration of a therapeutically effective amount of fms-like tyrosine kinase receptor (flt-1) VEGFR-1.
  - 28. The method of claim 20, which further comprises administration of chemotherapeutic agent.
  - 29. The method of claim 20, which further comprises administration of radiation.
  - 30. The method of claim 20, wherein the antibody neutralizes KDR.

10. An isolated polynucleotide which comprises a nucleotide sequence that encodes an amino acid sequence selected from the group consisting of SEQ ID NO:
- 20, SEQ ID NO;
  
  22, SEQ ID NO;
  
  24, SEQ ID NO;
  
  26, SEQ ID NO;
  
  29, SEQ ID NO;
  
  31, SEQ ID NO;
  
  33, SEQ ID NO;
  
  35, SEQ ID NO;
  
  37, SEQ ID NO;
  
  39, SEQ ID NO;
  
  41, SEQ ID NO;
  
  43, SEQ ID NO;
  
  45, SEQ ID NO;
  
  47, SEQ ID NO;
  
  49, SEQ ID NO;
  
  51, and SEQ ID NO;
  
  53.
- View Dependent Claims (11, 12, 13, 14, 15, 16, 17)
- - 11. The polynucleotide of claim 10, wherein the nucleotide sequence is SEQ ID NO:
    - 23.
  - 12. The polynucleotide of claim 10, wherein the nucleotide sequence is SEQ ID NO:
    - 25.
  - 13. The polynucleotide of claim 10, wherein the nucleotide sequence is SEQ ID NO:
    - 52.
  - 14. An expression vector comprising the polynucleotide of claim 10.
  - 15. A recombinant host cell comprising the expression vector of claim 14.
  - 16. The recombinant host cell of claim 15 which produces a polypeptide comprising SEQ ID NO:
    - 24 and a polypeptide comprising SEQ ID NO;
      
      26.
  - 17. The recombinant host cell of claim 15 which produces a polypeptide comprising SEQ ID NO:
    - 24 and a polypeptide comprising SEQ ID NO;
      
      53.

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Current Assignee
IMCLONE LLC
Original Assignee
IMCLONE LLC
Inventors
Zhu, Zhenping

Granted Patent

US 7,498,414 B2
Time in Patent Office

Days
Field of Search
US Class Current

530/388.220
CPC Class Codes

A61K 2039/505   comprising antibodies

A61P 35/00   Antineoplastic agents

A61P 35/02   specific for leukemia

A61P 43/00   Drugs for specific purposes...

A61P 9/00   Drugs for disorders of the ...

C07K 16/2863   against receptors for growt...

C07K 2317/21   from primates, e.g. man

C07K 2317/55   Fab or Fab'

C07K 2317/56   variable (Fv) region, i.e. ...

C07K 2317/565   Complementarity determining...

C07K 2317/622   Single chain antibody (scFv)

C07K 2317/76   Antagonist effect on antige...

C07K 2317/92   Affinity (KD), association ...

Human antibodies specific to kdr and uses thereof

First Claim

2 Assignments

0 Petitions

Accused Products

Abstract

49 Citations

30 Claims

Specification

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Human antibodies specific to kdr and uses thereof

First Claim

2 Assignments

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0 Petitions

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Accused Products

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Abstract

49 Citations

30 Claims

Specification

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Solutions

Use Cases

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