Anti-complement C1s antibodies

• US 8,945,562 B2
• Filed: 11/01/2013
• Issued: 02/03/2015
• Est. Priority Date: 11/02/2012
• Status: Active Grant

• Current Assignee: Bioverativ USA Inc.
• Original Assignee: True North Therapeutics, Inc. (Sanofi )
• Inventors: Van Vlasselaer, Peter, Parry, Graham, Stagliano, Nancy E., Panicker, Sandip
• Primary Examiner(s): Gambel, Phillip
• Application Number:
  US14/070,186
• Publication Number:
  US 20140140933A1
• Time in Patent Office: 459 Days
• Field of Search: None
• US Class Current: 424/145.1
• CPC Class Codes: A01N 1/021 Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 49/00 Preparations for testing in vivo
• CPC Class Codes: A61K 49/16 Antibodies; Immunoglobulins; Fragments thereof
• CPC Class Codes: A61K 51/10 Antibodies or immunoglobulins; Fragments thereof , the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• 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 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/08 Antiseborrheics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• 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 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 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 27/10 : for accommodation disorders, e.g. myopia
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 7/08 : Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock artificial tears A61P27/04
• CPC Class Codes: A61P 7/10 : Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 16/18 : against material from animals or humans
• CPC Class Codes: C07K 16/40 : against enzymes
• CPC Class Codes: C07K 2317/21 : from primates, e.g. man
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/33 : Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/34 : Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/35 : Valency
• CPC Class Codes: C07K 2317/54 : F(ab')2
• CPC Class Codes: C07K 2317/55 : Fab or Fab'
• CPC Class Codes: C07K 2317/56 : variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2319/00 : Fusion polypeptide
• CPC Class Codes: C12Y 304/21042 : Complement subcomponent C1s (3.4.21.42)
• CPC Class Codes: G01N 2800/52 : Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/6893 : related to diseases not provided for elsewhere

Abstract

The present disclosure provides antibodies that bind complement C1s protein; and nucleic acid molecules that encode such antibodies. The present disclosure also provides compositions comprising such antibodies, and methods to produce and use such antibodies, nucleic acid molecules, and compositions.

Claims

1. A container comprising a composition comprising a humanized antibody that binds complement C1s protein and comprises light chain complementarity determining regions (CDRs) of an antibody light chain variable region comprising amino acid sequence SEQ ID NO:

7 and heavy chain CDRs of an antibody heavy chain variable region comprising amino acid sequence SEQ ID NO;

8.

2. The container of claim 1, wherein the container is sterile.

3. The container of claim 1, wherein the container is a vial.

4. The container of claim 1, wherein the container is a bottle.

5. The container of claim 1, wherein the container is a syringe.

6. The container of claim 1, wherein the composition comprises a pharmaceutically acceptable excipient.

7. The container of claim 1, wherein the humanized antibody comprises a humanized light chain framework region.

8. The container of claim 1, wherein the humanized antibody comprises a humanized heavy chain framework region.

9. The container of claim 1, wherein the humanized antibody comprises a humanized light chain framework region and a humanized heavy chain framework region.

10. The container of claim 1, wherein the humanized antibody comprises a heavy chain constant region of the isotype IgG1, IgG2, IgG3, or IgG4.

11. The container of claim 1, wherein the humanized antibody is selected from the group consisting of a Fab fragment, a F(ab′

)₂ fragment, a scFv, and a Fv.

12. A lyophilized composition comprising a humanized antibody that binds complement C1s protein and comprises light chain complementarity determining regions (CDRs) of an antibody light chain variable region comprising amino acid sequence SEQ ID NO:

7 and heavy chain CDRs of an antibody heavy chain variable region comprising amino acid sequence SEQ ID NO;

8.

13. The lyophilized composition of claim 12, comprising a lyoprotectant.

14. The lyophilized composition of claim 12, wherein the humanized antibody comprises a humanized light chain framework region.

15. The lyophilized composition of claim 12, wherein the humanized antibody comprises a humanized heavy chain framework region.

16. The lyophilized composition of claim 12, wherein the humanized antibody comprises a humanized light chain framework region and a humanized heavy chain framework region.

17. The lyophilized composition of claim 12, wherein the humanized antibody comprises a heavy chain constant region of the isotype IgG1, IgG2, IgG3, or IgG4.

18. The lyophilized composition of claim 12, wherein the humanized antibody is selected from the group consisting of a Fab fragment, a F(ab′

)₂ fragment, a scFv, and a Fv.

19. A composition comprising:

a) a humanized antibody comprising;

i) a light chain variable region comprising a complementarity-determining region (CDR) comprising a CDR-L1 having the amino acid sequence of SEQ ID NO;

1, a CDR-L2 having the amino acid sequence of SEQ ID NO;

2, a CDR-L3 having the amino acid sequence of SEQ ID NO;

3; and

ii) a heavy chain variable region comprising a CDR comprising a CDR-H1 having amino acid sequence SEQ ID NO;

4, a CDR-H2 having amino acid sequence SEQ ID NO;

5, and a CDR-H3 having amino acid sequence SEQ ID NO;

6; and

b) a pharmaceutically acceptable excipient.

20. The composition of claim 19, wherein the composition comprises one or more of a tonicity agent, a suspending agent, an emulsifying agent, a stabilizer, a preservative, a lyoprotectant, a surfactant, and a sugar.

21. The composition of claim 19, wherein the composition comprises a tonicity agent.

22. The composition of claim 19, wherein the composition comprises a suspending agent.

23. The composition of claim 19, wherein the composition comprises an emulsifying agent.

24. The composition of claim 19, wherein the composition comprises a stabilizer.

25. The composition of claim 19, wherein the composition comprises a preservative.

26. The composition of claim 19, wherein the composition comprises a lyoprotectant.

27. The composition of claim 19, wherein the composition comprises a surfactant.

28. The composition of claim 19, wherein the composition comprises a sugar.

29. The composition of claim 28, wherein the sugar is trehalose or sucrose.

30. The composition of claim 19, wherein the humanized antibody comprises a humanized light chain framework region.

31. The composition of claim 19, wherein the humanized antibody comprises a humanized heavy chain framework region.

32. The composition of claim 19, wherein the humanized antibody comprises a humanized light chain framework region and a humanized heavy chain framework region.

33. The composition of claim 19, wherein the humanized antibody comprises a heavy chain constant region of the isotype IgG1, IgG2, IgG3, or IgG4.

34. The composition of claim 19, wherein the humanized antibody is selected from the group consisting of a Fab fragment, a F(ab′

)₂ fragment, a scFv, and a Fv.

35. A composition comprising:

a) a humanized antibody that binds complement C1s protein and comprises light chain complementarity-determining regions (CDRs) of an antibody light chain variable region comprising amino acid sequence SEQ ID NO;

7 and heavy chain CDRs of an antibody heavy chain variable region comprising amino acid sequence SEQ ID NO;

8,

wherein the humanized antibody comprises a humanized light chain framework region; and

b) a pharmaceutically acceptable excipient.

36. The composition of claim 35, wherein the humanized antibody comprises a humanized heavy chain framework region.

37. The composition of claim 35, wherein the humanized antibody comprises a heavy chain constant region of the isotype IgG1, IgG2, IgG3, or IgG4.

38. The composition of claim 35, wherein the humanized antibody is selected from the group consisting of a Fab fragment, a F(ab′

)₂ fragment, a scFv, and a Fv.

39. A composition comprising:

a) a humanized antibody that binds complement C1s protein and comprises light chain complementarity-determining regions (CDRs) of an antibody light chain variable region comprising amino acid sequence SEQ ID NO;

7 and heavy chain CDRs of an antibody heavy chain variable region comprising amino acid sequence SEQ ID NO;

8,

wherein the humanized antibody comprises a humanized heavy chain framework region; and

b) a pharmaceutically acceptable excipient.

40. The composition of claim 39, wherein the humanized antibody comprises a humanized light chain framework region.

41. The composition of claim 39, wherein the humanized antibody comprises a heavy chain constant region of the isotype IgG1, IgG2, IgG3, or IgG4.

42. The composition of claim 39, wherein the humanized antibody is selected from the group consisting of a Fab fragment, a F(ab′

)₂ fragment, a scFv, and a Fv.

43. A humanized antibody that binds complement C1s protein and comprises an antibody heavy chain variable region comprising amino acid sequence SEQ ID NO:

8 comprising one or more humanized heavy chain framework regions.

44. The humanized antibody of claim 43, wherein the humanized antibody comprises a humanized light chain framework region.

45. The humanized antibody of claim 43, wherein the humanized antibody comprises a heavy chain constant region of the isotype IgG1, IgG2, IgG3, or IgG4.

46. The humanized antibody of claim 43, wherein the humanized antibody is selected from the group consisting of a Fab fragment, a F(ab′

)₂ fragment, a scFv, and a Fv.

47. A composition comprising:

a) the humanized antibody of claim 43; and

b) a pharmaceutically acceptable excipient.