# US 8,784,823 B2 · Binding proteins, including antibodies, antibody derivatives and antibody fragments, that specifically bind CD154 and uses thereof

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- Number: US 8,784,823 B2
- Document ID: US8784823B2
- Status: Granted
- Kind: B2
- Application number: 13/656,922
- Filed: 2012-10-22
- Published: 2013-02-21
- Granted: 2014-07-22
- Earliest claimed: 2007-03-22
- Assignees: Biogen Idec MA Inc.; Ucb Biopharma Sprl
- Applicants: UCB Pharma S.A.; Biogen Idec MA Inc.
- Inventors: Linda C. Burkly; Janine L. Ferrant-Orgettas; Ellen A. Garber; Yen-Ming Hsu; Lihe Su; Frederick R. Taylor; Ralph Adams; Derek Thomas Brown; Andrew George Popplewell; Martyn Kim Robinson; Anthony Shock; Kerry Louise Tyson
- Web page: https://patentgrep.com/patent/US8784823B2

## CPC

- C07K 16/2875: {against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 (against NGF C07K16/22, against TNF C07K16/241)}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- 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 17/00: Drugs for dermatological disorders
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/04: for non-specific disorders of the connective tissue
- A61P 25/00: Drugs for disorders of the nervous system
- 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
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/40: characterized by post-translational modification
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/55: Fab or Fab'
- C07K 2317/71: Decreased effector function due to an Fc-modification
- C07K 2317/734: Complement-dependent cytotoxicity [CDC]
- 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
- 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)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This invention provides binding proteins, including antibodies, antibody derivatives and antibody fragments, that specifically bind a CD154 (CD40L) protein. This invention also provides a chimeric, humanized or fully human antibody, antibody derivative or antibody fragment that specifically binds to an epitope to which a humanized Fab fragment comprising a variable heavy chain sequence according to SEQ ID NO: 1 and comprising a variable light chain sequence according to SEQ ID NO: 2 specifically binds. CD154 binding proteins of this invention may elicit reduced effector function relative to a second anti-CD154 antibody. CD154 binding proteins of this invention are useful in diagnostic and therapeutic methods, such as in the treatment and prevention of diseases including those that involve undesirable immune responses that are mediated by CD154-CD40 interactions.

## Claims

### Claim 1

A method for treating a human condition, disorder or disease mediated in whole or in part by CD40 signaling, or a symptom of any of the foregoing, the method comprising the step of administering to a subject in need thereof a therapeutically effective amount of a CD154 binding protein comprising heavy chain CDR1, CDR2 and CDR3 sequences selected from:
(a) SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5, respectively;
(b) SEQ ID NO: 42, SEQ ID NO: 43 and SEQ ID NO: 44, respectively; or
(c) SEQ ID NO: 48, SEQ ID NO: 49 and SEQ ID NO: 50, respectively;
and comprising light chain CDR1, CDR2 and CDR3 sequences selected from:
(a) SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8, respectively;
(b) SEQ ID NO: 45, SEQ ID NO: 46 and SEQ ID NO: 47, respectively; or
(c) SEQ ID NO: 51, SEQ ID NO: 52 and SEQ ID NO: 53, respectively,
wherein the condition, disorder or disease is an inflammatory or autoimmune response or fibrosis.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the inflammatory or autoimmune response or fibrosis is selected from lupus nephritis, rheumatoid arthritis, systemic lupus erythematosis, spondyloarthritis, inflammatory bowel disease, Crohn's disease, psoriasis and multiple sclerosis.

### Claim 3

A method for treating a human condition, disorder or disease mediated in whole or in part by CD40 signaling, or a symptom of any of the foregoing, the method comprising the step of administering to a subject in need thereof a therapeutically effective amount of a composition of a CD154 binding protein comprising heavy chain CDR1, CDR2 and CDR3 sequences selected from:
(a) SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5, respectively;
(b) SEQ ID NO: 42, SEQ ID NO: 43 and SEQ ID NO: 44, respectively; or
(c) SEQ ID NO: 48, SEQ ID NO: 49 and SEQ ID NO: 50, respectively;
and comprising light chain CDR1, CDR2 and CDR3 sequences selected from:
(a) SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8, respectively;
(b) SEQ ID NO: 45, SEQ ID NO: 46 and SEQ ID NO: 47, respectively; or
(c) SEQ ID NO: 51, SEQ ID NO: 52 and SEQ ID NO: 53, respectively,
wherein the condition, disorder or disease is an inflammatory or autoimmune response or fibrosis.

### Claim 4 (depends on 3)

The method according to claim 3, wherein the inflammatory or autoimmune response or fibrosis is selected from rheumatoid arthritis, systemic lupus erythematosis, drug-induced lupus erythematosus, lupus nephritis, spondyloarthritis, inflammatory bowel disease, Crohn's disease, psoriasis and multiple sclerosis.

### Claim 5 (depends on 4)

The method according to claim 4, wherein said inflammatory or autoimmune response or fibrosis is lupus nephritis.

### Claim 6 (depends on 4)

The method according to claim 4, wherein said inflammatory or autoimmune response or fibrosis is systemic lupus erythematosis.

### Claim 7 (depends on 4)

The method according to claim 4, wherein said inflammatory or autoimmune response or fibrosis is drug-induced lupus erythematosus.