Human trk receptors and neurotrophic factor inhibitors

• US 5,910,574 A
• Filed: 05/31/1995
• Issued: 06/08/1999
• Est. Priority Date: 03/18/1994
• Status: Expired due to Term

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Urfer, Roman, Presta, Leonard G., Shelton, David L.
• Primary Examiner(s): Huff, Sheela
• Assistant Examiner(s): Reeves, Julie E
• Application Number:
  US08/457,880
• Time in Patent Office: 1,469 Days
• Field of Search: 530/388.1, 530/387.3, 530/388.22, 514/2, 424/130.1, 424/143.1, 424/133.1
• US Class Current: 530/388.22
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 14/71 for growth factors; for growth regulators
• CPC Class Codes: C07K 19/00 Hybrid peptides , i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/30 : Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

The invention concerns human trkB and trkC receptors and their functional derivatives. The invention further concerns immunoadhesins comprising trk receptor sequences fused to immunoglobulin sequences.

Claims

1. A monoclonal antibody or antigen-binding fragment thereof, that specifically binds a polypeptide comprising an amino acid sequence selected from the group consisting of:

(a) mature human trkB in SEQ ID NO;

2;

(b) mature human trkC in SEQ ID NO;

6;

(c) trk B or trk C polyphide encode by a naturally-occurring allelic variant or splice variant of (a) or (b); and

,

(d) a neurotrophin-binding, second immunoglobulin-like C2-type domain of (a), (b), or (c).

2. A hybridoma cell line producing the antibody or antigen-binding fragment of claim 1.

3. A composition comprising an antibody or antigen-binding fragment of claim 1 in admixture with a physiologically acceptable carrier.

4. The antibody or antigen-binding fragment of claim 1 that is an antagonist of human trkB or human trkC.

5. The antibody or antigen-binding fragment of claim 1 that is humanized.

6. The antibody or antigen-binding fragment of claim 1 that is a human antibody or antigen-binding fragment thereof.

7. The antibody or antigen-binding fragment of claim 1, wherein the selected amino acid sequence is (a) or (b).

8. The antibody or antigen-binding fragment of claim 7, wherein the selected amino acid sequence is (b).

9. The antibody or antigen-binding fragment of claim 1, wherein the selected amino acid sequence is from (c).

10. The antibody or antigen-binding fragment of claim 9, wherein the selected amino acid sequence from (c) is encoded by a naturally-occurring allelic variant or splice variant of (b).

11. The monoclonal antibody or antigen-binding fragment of claim 1, wherein the amino acid sequence is selected the group consisting of:

(a) mature human trkC in SEQ ID NO;

6;

(b) trkC polypeptide encoded by a naturally-occurring allelic variant or splice variant of (a); and

(c) a neurotrophin-binding, second immunoglobulin-like C2-type domain of (a) or (b).

12. The monoclonal antibody or antigen-binding fragment of claim 11, wherein the amino acid is selected from group (c).

13. A monoclonal antibody or antigen-binding fragment thereof that specifically binds to a polypeptide having an amino acid sequence selected from the group consisting of:

(a) from about amino acid residue 301 to about amino acid residue 365 in SEQ. ID. NO;

2; and

(b) from about amino acid residue 313 to about amino acid residue 376 in SEQ. ID. NO;

6.

14. A monoclonal antibody or antigen-binding fragment thereof that specifically binds a polypeptide comprising an amino acid sequence selected from the group consisting of:

(a) mature human trkB in SEQ ID NO;

2;

(b) mature human trkC in SEQ ID NO;

6;

(c) trkB or trkC polypephide encoded by a naturally-occurring allelic variant or splice variant of (a) or (b); and

(d) a neurotrophin-binding, second immunoglobulin-like C2-type domain of (a), (b), or (c),

wherein the antibody or antigen-binding fragment thereof is an agonist of human trkC or human trkB.

15. The monoclonal antibody of claim 14, wherein the antibody or antigen-binding fragment is an agonist of human trkC.