Antibodies to the C3d fragment of complement component 3

• US 9,815,890 B2
• Filed: 06/22/2011
• Issued: 11/14/2017
• Est. Priority Date: 06/22/2010
• Status: Expired

• Current Assignee: MUSC Foundation For Research Development (State of South Carolina), The Board of Regents of the University of Colorado (University of Colorado System)
• Original Assignee: The Board of Regents of the University of Colorado (University of Colorado System)
• Inventors: Holers, V. Michael, Thurman, Joshua M., Kulik, Liudmila, Tomlinson, Stephen
• Primary Examiner(s): Gambel, Phillip
• Application Number:
  US13/805,522
• Publication Number:
  US 20130129728A1
• Time in Patent Office: 2,337 Days
• Field of Search: None
• 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 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• 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 25/28 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• 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 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 7/10 : Antioedematous agents; Diuretics
• 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 14/472 : Complement proteins, e.g. anaphylatoxin, C3a, C5a
• CPC Class Codes: C07K 16/18 : against material from animals or humans
• CPC Class Codes: C07K 2317/33 : Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• 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

Abstract

The present invention relates to methods and materials for modulating the complement alternative pathway (CAP), the complement classical pathway (CCP), the complement lectin/mannose pathway (CMP), or combinations thereof, as well as methods and materials for targeting diagnostic, prophylactic and therapeutic agents to localized areas of tissue within the body where they may more directly exert their effects upon the intended target cells or tissue, with reduced, associated systemic effects compared with administration of the same or similar agents in an untargeted, systemic manner. The methods and materials of the present invention may therefore allow for increased efficacy, lower threshold effective dosages and/or lower effective maintenance doses, and/or reduced associated undesired or adverse effects in terms of frequency or severity of occurrence, or both. The present invention also relates to methods and materials for modulating a host humoral immune response, especially reducing, inhibiting, or preventing a host humoral immune response.

Claims

1. An isolated antibody or antigen-binding fragment thereof, comprising the complementarity determining regions of an antibody selected from the group consisting of:

i) 3db8 produced by hybridoma cell line 3d-8b/2 (ATCC Deposit PTA-10999);

ii) 3d9a produced by hybridoma cell line 3d-9a/25 (ATCC Deposit PTA-10998);

iii) 3d29 produced by hybridoma cell line 3d-29/5/2 (ATCC Deposit PTA-11000)

iv) 3d11 produced by hybridoma cell line 3d-11/14 (ATCC Deposit PTA-10011);

v) 3d31 produced by hybridoma cell line 3d-31/A6/9 (ATCC Deposit PTA-11027);

vi) 3d3 produced by hybridoma cell line 3d-3/28/4 (ATCC Deposit PTA-11025)

vii) 3d15 produced by hybridoma cell line 3d-15A9 (ATCC Deposit PTA-11012);

viii) 3d10 produced by hybridoma cell line 3d-10/14/1 (ATCC Deposit PTA-11010); and

ix) 3d16 produced by hybridoma cell line 3d-16/3/3 (ATCC Deposit PTA-11026);

wherein said isolated antibody or antigen-binding fragment thereof is capable of specifically binding to a mammalian complement component C3d protein.

2. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein said antibody or antigen-binding fragment thereof is a humanized, primatized, or chimerized antibody or antigen-binding fragment thereof.

3. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein said antibody or antigen-binding fragment thereof is selected from the group consisting of:

a monoclonal antibody or antibody fragment, a single chain antibody, an Fv, an Fab, an Fab′

, and an F(ab′

)₂.

4. The isolated antibody of claim 3, wherein said antibody is a monoclonal antibody.

5. The isolated antibody of claim 4, wherein said antibody is selected from the group consisting of:

i) 3db8 produced by hybridoma cell line 3d-8b/2 (ATCC Deposit PTA-10999);

ii) 3d9a produced by hybridoma cell line 3d-9a/25 (ATCC Deposit PTA-10998);

iii) 3d29 produced by hybridoma cell line 3d-29/5/2 (ATCC Deposit PTA-11000)

iv) 3d11 produced by hybridoma cell line 3d-11/14 (ATCC Deposit PTA-10011);

v) 3d31 produced by hybridoma cell line 3d-31/A6/9 (ATCC Deposit PTA-11027);

vi) 3d3 produced by hybridoma cell line 3d-3/28/4 (ATCC Deposit PTA-11025)

vii) 3d15 produced by hybridoma cell line 3d-15A9 (ATCC Deposit PTA-11012);

viii) 3d10 produced by hybridoma cell line 3d-10/14/1 (ATCC Deposit PTA-11010); and

ix) 3d16 produced by hybridoma cell line 3d-16/3/3 (ATCC Deposit PTA-11026).

7. A pharmaceutical composition comprising the isolated antibody or antigen-binding fragment thereof of claim 1 and a pharmaceutically-acceptable excipient.

8. A therapeutic kit comprising:

(i) the antibody or antigen-binding fragment of claim 1, and

(ii) means for delivering the antibody or antigen-binding fragment to a human.

9. A pre-filled syringe comprising the antibody or antigen-binding fragment thereof of claim 1.

10. The isolated antibody or antigen-binding fragment thereof of claim 1, comprising the complementarity determining regions of the antibody 3db8 produced by hybridoma cell line 3d-8b/2 (ATCC Deposit PTA-10999).

11. The isolated antibody or antigen-binding fragment thereof of claim 1, comprising the complementarity determining regions of the antibody 3d9a produced by hybridoma cell line 3d-9a/25 (ATCC Deposit PTA-10998).

12. The isolated antibody or antigen-binding fragment thereof of claim 1, comprising the complementarity determining regions of the antibody 3d29 produced by hybridoma cell line 3d-29/5/2 (ATCC Deposit PTA-11000).

13. The isolated antibody or antigen-binding fragment thereof of claim 1, comprising the complementarity determining regions of the antibody 3d11 produced by hybridoma cell line 3d-11/14 (ATCC Deposit PTA-10011).

14. The isolated antibody or antigen-binding fragment thereof of claim 1, comprising the complementarity determining regions of the antibody 3d31 produced by hybridoma cell line 3d-31/A6/9 (ATCC Deposit PTA-11027).

15. The isolated antibody or antigen-binding fragment thereof of claim 1, comprising the complementarity determining regions of the antibody 3d3 produced by hybridoma cell line 3d-3/28/4 (ATCC Deposit PTA-11025).

16. The isolated antibody or antigen-binding fragment thereof of claim 1, comprising the complementarity determining regions of the antibody 3d15 produced by hybridoma cell line 3d-15A9 (ATCC Deposit PTA-11012).

17. The isolated antibody or antigen-binding fragment thereof of claim 1, comprising the complementarity determining regions of the antibody 3d10 produced by hybridoma cell line 3d-10/14/1 (ATCC Deposit PTA-11010).

18. The isolated antibody or antigen-binding fragment thereof of claim 1, comprising the complementarity determining regions of the antibody 3d16 produced by hybridoma cell line 3d-16/3/3 (ATCC Deposit PTA-11026).

6. A hybridoma cell selected from the group consisting of:

3d-8b/2 (ATCC Deposit PTA-10999), 3d-9a/25 (ATCC Deposit number;

PTA-10998), 3d-29/5/2 (ATCC Deposit number;

PTA-11000), 3d-11/14 (ATCC Deposit number;

PTA-11011), 3d-31/A6/9 (ATCC Deposit number;

PTA-11027), 3d-3/28/4 (ATCC Deposit number;

PTA-11025), 3d-15A9 (ATCC Deposit number;

PTA-11012), 3d-10/14/1 (ATCC Deposit number;

PTA-11010), and 3d-16/3/3 (ATCC Deposit number;

PTA-11026).