Anti-complement C1s antibodies

• US 10,450,382 B2
• Filed: 12/20/2016
• Issued: 10/22/2019
• Est. Priority Date: 11/02/2012
• Status: Active Grant

• Current Assignee: Bioverativ USA Inc. (Sanofi )
• Original Assignee: Bioverativ USA Inc. (Sanofi )
• Inventors: Van Vlasselaer, Peter, Parry, Graham, Stagliano, Nancy E., Panicker, Sandip
• Primary Examiner(s): Gambel, Phillip
• Application Number:
  US15/385,735
• Publication Number:
  US 20170226230A1
• Time in Patent Office: 1,036 Days
• Field of Search: None
• 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 humanized antibody that binds complement C1s protein and comprises:

a light chain variable region that comprises a CDR-L1 amino acid sequence set forth in SEQ ID NO;

1, a CDR-L2 amino acid sequence set forth in SEQ ID NO;

2, and a CDR-L3 amino acid sequence set forth in SEQ ID NO;

3;

a heavy chain variable region that comprises a CDR-H1 amino acid sequence set forth in SEQ ID NO;

4, a CDR-H2 amino acid sequence set forth in SEQ ID NO;

5, and a CDR-H3 amino acid sequence set forth in SEQ ID NO;

6; and

an IgG4 constant region comprising an S241P substitution (by Kabat numbering) and an L235E substitution (by EU numbering).

2. A pharmaceutical composition comprising the humanized antibody of claim 1 and a pharmaceutically-acceptable excipient.

3. A humanized antibody that binds complement C1s protein and comprises:

a CDR-L1 sequence, a CDR-L2 sequence, and a CDR-L3 sequence of an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO;

44;

a CDR-H1 sequence, a CDR-H2 sequence, and a CDR-H3 sequence of an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO;

42; and

an IgG4 constant region comprising an S241P substitution (by Kabat numbering) and an L235E substitution (by EU numbering).

4. A pharmaceutical composition comprising the humanized antibody of claim 3 and a pharmaceutically-acceptable excipient.

5. A humanized antibody that binds complement C1s protein and comprises:

an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO;

44;

an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO;

42; and

an IgG4 constant region comprising an S241P substitution (by Kabat numbering) and an L235E substitution (by EU numbering).

6. A pharmaceutical composition comprising the humanized antibody of claim 5 and a pharmaceutically-acceptable excipient.

7. A pharmaceutical composition comprising a humanized antibody that binds complement C1s protein and comprises:

an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO;

44;

an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO;

42; and

a pharmaceutically-acceptable excipient.

8. The pharmaceutical composition of claim 7, wherein the humanized antibody further comprises an IgG4 constant region.

9. The pharmaceutical composition of claim 8, wherein the IgG4 constant region comprises an S241P substitution (by Kabat numbering) and an L235E substitution (by EU numbering).