# US 6,001,358 A · Humanized antibodies to human gp39, compositions containing thereof

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- Number: US 6,001,358 A
- Document ID: US6001358A
- Status: Granted
- Kind: A
- Application number: 08/554,840
- Filed: 1995-11-07
- Granted: 1999-12-14
- Earliest claimed: 1995-11-07
- Assignees: IDEC Pharmaceuticals Corporation
- Inventors: Amelia Black; Nabil Hanna; Eduardo A. Padlan; Roland A. Newman
- Web page: https://patentgrep.com/patent/US6001358A

## CPC

- C07K 16/2875: {against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 (against NGF C07K16/22, against TNF C07K16/241)}
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/06: Antipsoriatics
- A61P 27/00: Drugs for disorders of the senses
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/04: Immunostimulants
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- C07K 16/467: {Igs with modifications in the FR-residues only}
- 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)
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- G01N 2333/70578: NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30 CD40 or CD95
- G01N 2800/24: Immunology or allergic disorders
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention is directed to humanized antibodies which bind human gp39 and their use as therapeutic agents. These humanized antibodies are especially useful for treatment of autoimmune diseases.

## Claims

### Claim 1

A humanized antibody or antigen-binding fragment thereof that specifically binds the CD40 ligand wherein said humanized antibody or fragment thereof contains a variable light sequence which comprises the amino acid sequence encoded by the nucleic acid sequence having SEQ ID No. 24 or SEQ ID No. 25 and the said humanized antibody or fragment thereof contains a variable heavy sequence which comprises the amino acid sequence encoded by the nucleic acid sequence having SEQ ID No. 26.

### Claim 2 (depends on 1)

The humanized antibody or antigas-binding fragment of claim 1, wherein the variable light sequence has the amino acid sequence encoded by the nucleic acid sequence having SEQ ID No. 24.

### Claim 3 (depends on 1)

The humanized antibody or antigas-binding fragment of claim 1, wherein the variable ligand sequence has the amino acid sequence encoded by the nucleic acid sequence having SEQ ID No. 25.

### Claim 4 (depends on 1)

The humanized antibody of claim 1, which comprises human heavy and light constant domains.

### Claim 5 (depends on 4)

The humanized antibody of claim 4, wherein the human suitable heavy constant region is selected from the group consisting of human gamma 1, human gamma 2, human gamma 3, human gamma 4.

### Claim 6 (depends on 4)

The humanized antibody of claim 4, wherein the human variable heavy constant region is gamma 4 or a mutated gamma 4 which contains either or both of the following modifications:
(i) change of a leucine to a glutamic acid at position 236 (according to the Kabat numbering system); and
(ii) change of a serine to a proline at position 229 (according to the Kabat numbering system).

### Claim 7 (depends on 6)

The humanized antibody of claim 6, which comprises a mutated gamma 4 containing both of said modifications.

### Claim 8 (depends on 4)

The humanized antibody of claim 4, wherein the human light constant region is the Kappa or lambda constant region.

### Claim 9 (depends on 4)

The humanized antibody according to claim 4 which comprises the human Kappa light chain constant region and human gamma 4 heavy chain constant region or a mutated human gamma 4 heavy chain constant region, wherein the mutated gamma 4 heavy chain comprises either or both of the following modifications:
(i) the change of a leucine to glutamic acid at position 236 according to the Kabat numbering system; and
(ii) the change of a serine to proline at position 229 according to the Kabat numbering system.

### Claim 10 (depends on 1)

A humanized antibody according to claim 1, which contains one or more of the following modifications:
(i) substitution of the amino acid residue at one or more of positions 34, 43, 44 and 68 of the variable heavy sequence (according to Kabat numbering scheme) with a different amino acid;
(ii) substitution of residue 85 of the variable light chain (according to the Kabat numbering scheme) with a different amino acid.

### Claim 11 (depends on 1)

The humanized antibody according to the claim 1, which further comprises one or more conservative amino acid substitutions which do not adversely affect CD40 ligand binding.

### Claim 12 (depends on 1)

A pharmaceutical composition containing a therapeutically effective amount of a humanized antibody or antigen binding domain according to claim 1, and a pharmaceutically acceptable carrier.