POLYPEPTIDES THAT BIND TO HUMAN COMPLEMENT COMPONENT C5

• US 20130273052A1
• Filed: 09/30/2011
• Published: 10/17/2013
• Est. Priority Date: 10/01/2010
• Status: Abandoned Application

• Current Assignee: Alexion Pharmaceuticals Incorporated (Astrazeneca PLC)
• Original Assignee: Alexion Pharmaceuticals Incorporated (Astrazeneca PLC)
• Inventors: Gies, David, Springhorn, Jeremy P., Hunter, Jeffrey W.
• Application Number:
  US13/877,298
• Publication Number:
  US 20130273052A1
• Time in Patent Office: Days
• US Class Current: 424/135.1
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 15/06 Antiabortive agents; Labour repressants
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• 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 16/18 : against material from animals or humans
• CPC Class Codes: C07K 16/38 : against protease inhibitors of peptide structure
• CPC Class Codes: C07K 2317/622 : Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/94 : Stability, e.g. half-life, pH, temperature or enzyme-resistance
• CPC Class Codes: F16C 11/04 : Pivotal connections hinges for doors, windows or wings E05D
• CPC Class Codes: Y10T 403/32041 : Universal
• CPC Class Codes: Y10T 403/32606 : Pivoted
• CPC Class Codes: Y10T 403/33 : Transverse rod to spaced plate surfaces

Abstract

The present disclosure relates to, inter alia, C5-binding polypeptides and use of the polypeptides in methods for treating or preventing complement-associated disorders. Also featured are therapeutics kits containing one or more of the C5-binding polypeptides and means for administering the polypeptides to a subject.

Claims

1. A polypeptide comprising:

(i) amino acids 1-107 depicted in SEQ ID NO;

2 and (ii) amino acids 125-246 depicted in SEQ ID NO;

2, with the proviso that the polypeptide is not a whole antibody.

5. The polypeptide of claim 1, wherein the polypeptide comprises the amino acid sequence depicted in SEQ ID NO:

2.

7. A fusion polypeptide comprising:

(a) the polypeptide of claim 1; and

(b) an amino acid sequence that is heterologous to amino acids 1-107 and 125-246 of SEQ ID NO;

2.

9. A fusion polypeptide comprising:

(a) the polypeptide of claim 1; and

(b) a targeting moiety that targets the polypeptide of (a) to a site of complement activation.

15. A nucleic acid encoding the polypeptide of claim 1.

16. The nucleic acid of claim 15, wherein the nucleic acid comprises the nucleotide sequence depicted in SEQ ID NO:

1.

17. A vector comprising the nucleic acid of claim 15.

18. The vector of claim 17, wherein the nucleic acid is operably linked to an expression control sequence.

19. A cell comprising the vector of claim 17.

23. A method for producing a polypeptide, the method comprising culturing the cell of claim 19 under conditions suitable for expression of the polypeptide or fusion polypeptide.

26. A pharmaceutical composition comprising:

the polypeptide of claim 1; and

a pharmaceutically acceptable carrier.

32. A method for inhibiting formation of terminal complement in a biological sample, the method comprising contacting a biological sample with a therapeutic agent in an amount effective to inhibit terminal complement in the biological sample, wherein the biological sample is capable of terminal complement production in the absence of the therapeutic agent and wherein the therapeutic agent is the polypeptide of claim 1.

35. A method for treating a subject having a complement-associated disorder, the method comprising administering to the subject having a complement-associated disorder a therapeutic agent in an amount effective to treat the complement-associated disorder, wherein the therapeutic agent is the polypeptide of claim 1.

42. The method of claim 35, wherein the complement-associated disorder is selected from the group consisting of rheumatoid arthritis, a pulmonary condition, ischemia-reperfusion injury, atypical hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, paroxysmal nocturnal hemoglobinuria, dense deposit disease, age-related macular degeneration, spontaneous fetal loss, Pauci-immune vasculitis, epidermolysis bullosa, recurrent fetal loss, multiple sclerosis, traumatic brain injury, myasthenia gravis, cold agglutinin disease, dermatomyositis, Degos'"'"' disease, Graves'"'"' disease, Hashimoto'"'"'s thyroiditis, type I diabetes, psoriasis, pemphigus, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, Goodpasture syndrome, multifocal motor neuropathy, neuromyelitis optica, antiphospholipid syndrome, and catastrophic antiphospholipid syndrome.

43. The method of claim 42, wherein the pulmonary condition is selected from the group consisting of chronic obstructive pulmonary disorder (COPD), asthma, pulmonary fibrosis, bronchitis, emphysema, bronchiolitis obliterans, and sarcoidosis.

47. The method of claim 35, further comprising administering one or more additional therapeutic agents for treating a complement-associated disorder.

49. A conjugate comprising:

(i) the polypeptide of claim 1; and

(ii) a heterologous moiety conjugated to the polypeptide.

54. A kit for use in treating a subject having, suspected of having, or at risk for developing a complement-associated disorder, the kit comprising:

(i) a therapeutic agent selected from the group consisting of the polypeptides of claim 1; and

(ii) a means for delivering the therapeutic agent.

2. A polypeptide comprising an amino acid sequence that is at least 80% identical to an amino acid sequence comprising:

(i) amino acids 1-107 depicted in SEQ ID NO;

2 and (ii) amino acids 125-246 depicted in SEQ ID NO;

2, wherein the polypeptide binds to human complement component C5 and the amino acid sequence of the polypeptide comprises the glutamine residue at position 38 of SEQ ID NO;

2, with the proviso that the polypeptide is not a whole antibody.

3. (canceled)

4. A polypeptide that comprises at least 50 contiguous amino acids of SEQ ID NO:

2, wherein the polypeptide binds to human complement component C5 and the at least 50 amino acids comprise the glutamine residue at position 38 of SEQ ID NO;

2, with the proviso that the polypeptide is not a whole antibody.

6. (canceled)

8. (canceled)

10-14. -14. (canceled)

20-22. -22. (canceled)

24. (canceled)

25. (canceled)

27-31. -31. (canceled)

33. (canceled)

34. (canceled)

36-41. -41. (canceled)

44-46. -46. (canceled)

48. (canceled)

50-53. -53. (canceled)

55-63. -63. (canceled)