Agonist anti-trkC antibodies and methods using same

• US 7,968,690 B2
• Filed: 12/23/2004
• Issued: 06/28/2011
• Est. Priority Date: 12/23/2003
• Status: Active Grant

• Current Assignee: NXP B.V. (NXP Semiconductors NV)
• Original Assignee: Rinat Neuroscience Corp. (Pfizer Inc.)
• Inventors: Pons, Jaume
• Primary Examiner(s): GUSSOW, ANNE
• Application Number:
  US10/584,443
• Publication Number:
  US 20090202526A1
• Time in Patent Office: 2,378 Days
• Field of Search: None
• US Class Current: 530/388.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: C07K 16/2863 against receptors for growth factors, growth regulators
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/75 Agonist effect on antigen
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The invention concerns agonist anti-trkC antibodies, polypeptides, and polynucleotides encoding the same. The invention further concerns use of such antibodies, polypeptides and/or polynucleotides in the treatment and/or prevention of neuropathies, such as sensory neuropathies, including taxol-induced sensory neuropathy, cisplatin-induced sensory neuropathy, and pyridoxine-induced sensory neuropathy.

Claims

1. An isolated agonist anti-trkC antibody comprising:

(a) heavy chain CDRs (CDRHs) comprising;

(i) a CDRH1 of the formula GYTFTSYXaaXaaH (SEQ ID NO;

16), wherein Xaa at position 8 is R or W, and Xaa at position 9 is I, L, R, or M;

(ii) a CDRH2 of the formula EIYPSNXaaRTNYNEKFXaaS (SEQ ID NO;

17), wherein Xaa at position 7 is A, T, S, or G; and

Xaa at position 16 is K or E, and

(iii) a CDRH3 of the formula KYYYGNXaaXaaRSWYFDV (SEQ ID NO;

18), wherein Xaa at position 7 is T or S;

wherein Xaa at position 8 is R, Q, K, S, or Y; and

(b) light chain CDRs (CDRL) comprising;

(i) a CDRL1 of the formula RASESXaaDXaaYGISFXaaXaa (SEQ ID NO;

19), wherein Xaa at position 6 is I or V;

Xaa at position 8 is N or S;

Xaa at position 14 is L or M;

Xaa at position 15 is A, T, or N;

(ii) a CDRL2 of the formula AASNXaaGS (SEQ ID NO;

20), wherein Xaa at position 5 is R, L, or Q; and

(iii) a CDRL3 of the formula QQSKXaaVPRT (SEQ ID NO;

21), wherein Xaa at position 5 is T, A, S, or E;

wherein the agonist anti-trkC antibody is not an antibody comprising (a) a heavy chain CDRs comprising a CDRH1 of SEQ ID NO;

22, a CDRH2 of SEQ ID NO;

23, and a CDRH3 of SEQ ID NO;

24; and

(b) light chain CDRs comprising a CDRL1 of SEQ ID NO;

25, a CDRL2 of SEQ ID NO;

26, and a CDRL3 of SEQ ID NO;

27.

2. The isolated agonist anti-trkC antibody of claim 1, wherein the agonist anti-trkC antibody binds human trkC.

3. The isolated agonist anti-trkC antibody of claim 2, wherein the agonist anti-trkC antibody binds to human trkC with a K_D less than about 5 nM.

4. The isolated agonist anti-trkC antibody of claim 2, wherein the agonist anti-trkC antibody further binds rodent trkC.

5. The isolated agonist anti-trkC antibody of claim 1, wherein the agonist anti-trkC antibody is a monoclonal antibody.

6. The isolated agonist anti-trkC antibody of claim 1, wherein the agonist anti-trkC antibody is a humanized antibody.

7. The isolated agonist anti-trkC antibody of claim 1, wherein the agonist anti-trkC antibody comprises a heavy chain CDRs (CDRH) comprising:

(a) a CDRH1 region of SEQ ID NO;

4;

(b) a CDRH2 region of SEQ ID NO;

5; and

(c) a CDRH3 region of SEQ ID NO;

6.

8. The isolated agonist anti-trkC antibody of claim 7, wherein the heavy chain variable region consists of the sequence of SEQ ID NO:

1.

9. The isolated agonist anti-trkC antibody of claim 1, wherein the agonist anti-trkC antibody comprises a light chain CDRs (CDRL) comprising:

(a) a CDRL1 region of SEQ ID NO;

7;

(b) a CDRL2 region of SEQ ID NO;

8; and

(c) a CDRL3 region of SEQ ID NO;

9.

10. The isolated agonist anti-trkC antibody of claim 9, wherein the light chain variable region consists of the sequence of SEQ ID NO:

2.

11. An isolated agonist anti-trkC antibody of claim 1, wherein the agonist anti-trkC antibody comprises

(a) CDRHs comprising:

(i) a CDRH1 of SEQ ID NO;

4;

(ii) a CDRH2 of SEQ ID NO;

5; and

(iii) a CDRH3 of SEQ ID NO;

6; and

(b) CDRLs comprising;

(i) a CDRL1 of SEQ ID NO;

7;

(b) a CDRL2 of SEQ ID NO;

8; and

(c) a CDRL3 of SEQ ID NO;

9.

12. The isolated agonist anti-trkC antibody of claim 11, wherein the heavy chain variable region consists of SEQ ID NO:

1, and the light chain variable region consists of the sequence of SEQ ID NO;

2.

13. The isolated agonist anti-trkC antibody of claim 11, wherein the heavy chain consists of the sequence of SEQ ID NO:

28, and the light chain variable region consists of the sequence of SEQ ID NO;

29.

14. A pharmaceutical composition comprising (a) an effective amount of the agonist anti-trkC antibody of claim 1 and (b) a pharmaceutical acceptable excipient.

15. A kit comprising the agonist anti-trkC antibody of claim 1.

16. An isolated polypeptide that binds to trkC, comprising:

(a) a CDRH1 of the formula GYTFTSYXaaXaaH (SEQ ID NO;

16), wherein Xaa at position 8 is R or W, and Xaa at position 9 is I, L, R, or M;

(b) a CDRH2 of the formula EIYPSNXaaRTNYNEKFXaaS (SEQ ID NO;

17), wherein Xaa at position 7 is A, T, S, or G; and

Xaa at position 16 is K or E; and

(c) a CDRH3 of the formula KYYYGNXaaXaaRSWYFDV (SEQ ID NO;

18), wherein Xaa at position 7 is T or S;

wherein Xaa at position 8 is R, Q, K, S, or Y;

wherein the polypeptide is not a polypeptide comprising CDRHs comprising a CDRH1 region of SEQ ID NO;

22, a CDRH2region of SEQ ID NO;

23, and a CDRH3 region of SEQ ID NO;

24; and

further comprising;

(d) a CDRL1 of the formula RASESXaaDXaaYGISFXaaXaa (SEQ ID NO;

19), wherein Xaa at position 6 is I or V;

Xaa at position 8 is N or S;

Xaa at position 14 is L or M;

Xaa at position 15 is A, T, or N;

(e) a CDRL2 of the formula AASNXaaGS (SEQ ID NO;

20), wherein Xaa at position 5 is R, L, or Q; and

(f) a CDRL3 of the formula QQSKXaaVPRT (SEQ ID NO;

21), wherein Xaa at position 5 is T, A, S, or E;

wherein the polypeptide is not a polypeptide comprising CDRLs comprising a CDRL1 region of SEQ ID NO;

25, a CDRL2 region of SEQ ID NO;

26, and a CDRL3 region of SEQ ID NO;

27.