Antibodies that bind human dendritic and epithelial cell 205 (DEC-205)

• US 8,236,318 B2
• Filed: 11/07/2008
• Issued: 08/07/2012
• Est. Priority Date: 11/07/2007
• Status: Active Grant

• Current Assignee: Celldex Therapeutics Incorporated
• Original Assignee: Celldex Therapeutics Incorporated
• Inventors: Keler, Tibor, He, Lizhen, Ramakrishna, Venky, Vitale, Laura A.
• Primary Examiner(s): Juedes, Amy
• Application Number:
  US12/266,745
• Publication Number:
  US 20090175880A1
• Time in Patent Office: 1,369 Days
• Field of Search: None
• US Class Current: 424/178.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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 13/08 of the prostate
• CPC Class Codes: A61P 13/10 of the bladder
• 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 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 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 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• 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 31/14 : for RNA viruses
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 31/20 : for DNA viruses
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/04 : Immunostimulants
• 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 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 5/40 : Mineralocorticosteroids, e.g. aldosterone; Drugs increasing or potentiating the activity of mineralocorticosteroids
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/08 : Vasodilators for multiple indications
• CPC Class Codes: C07K 16/2851 : against the lectin superfamily, e.g. CD23, CD72
• CPC Class Codes: C07K 2317/21 : from primates, e.g. man
• CPC Class Codes: C07K 2317/77 : Internalization into the cell
• 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

Isolated monoclonal antibodies which bind to human DEC-205 and related antibody-based compositions and molecules are disclosed. Also disclosed are pharmaceutical compositions comprising the antibodies, as well as therapeutic and diagnostic methods for using the antibodies.

Claims

1. A method for targeting an antigen to human DEC-205 in a human subject comprising administering to the human subject an antibody linked to an antigen, wherein the antibody comprises:

(a) a heavy chain variable region CDR1 comprising SEQ ID NO;

29;

a heavy chain variable region CDR2 comprising SEQ ID NO;

30;

a heavy chain variable region CDR3 comprising SEQ ID NO;

31;

a light chain variable region CDR1 comprising SEQ ID NO;

35;

a light chain variable region CDR2 comprising SEQ ID NO;

36; and

a light chain variable region CDR3 comprising SEQ ID NO;

37;

(b) a heavy chain variable region CDR1 comprising SEQ ID NO;

17;

a heavy chain variable region CDR2 comprising SEQ ID NO;

18;

a heavy chain variable region CDR3 comprising SEQ ID NO;

19;

a light chain variable region CDR1 comprising SEQ ID NO;

23;

a light chain variable region CDR2 comprising SEQ ID NO;

24; and

a light chain variable region CDR3 comprising SEQ ID NO;

25;

(c) a heavy chain variable region CDR1 comprising SEQ ID NO;

5;

a heavy chain variable region CDR2 comprising SEQ ID NO;

6;

a heavy chain variable region CDR3 comprising SEQ ID NO;

7;

a light chain variable region CDR1 comprising SEQ ID NO;

11;

a light chain variable region CDR2 comprising SEQ ID NO;

12; and

a light chain variable region CDR3 comprising SEQ ID NO;

13;

(d) a heavy chain variable region CDR1 comprising SEQ ID NO;

41;

a heavy chain variable region CDR2 comprising SEQ ID NO;

42;

a heavy chain variable region CDR3 comprising SEQ ID NO;

43;

a light chain variable region CDR1 comprising SEQ ID NO;

47;

a light chain variable region CDR2 comprising SEQ ID NO;

48; and

a light chain variable region CDR3 comprising SEQ ID NO;

49;

(e) a heavy chain variable region CDR1 comprising SEQ ID NO;

53;

a heavy chain variable region CDR2 comprising SEQ ID NO;

54;

a heavy chain variable region CDR3 comprising SEQ ID NO;

55;

a light chain variable region CDR1 comprising SEQ ID NO;

59;

a light chain variable region CDR2 comprising SEQ ID NO;

60; and

a light chain variable region CDR3 comprising SEQ ID NO;

61;

or

(f) a heavy chain variable region CDR1 comprising SEQ ID NO;

77;

a heavy chain variable region CDR2 comprising SEQ ID NO;

78;

a heavy chain variable region CDR3 comprising SEQ ID NO;

79;

a light chain variable region CDR1 comprising SEQ ID NO;

83;

a light chain variable region CDR2 comprising SEQ ID NO;

84; and

a light chain variable region CDR3 comprising SEQ ID NO;

85, and

wherein the antibody binds to human DEC-205 comprising SEQ ID NO;

1.

2. The method of claim 1, wherein the antibody comprises:

(a) a heavy chain variable region CDR1 comprising SEQ ID NO;

29;

(b) a heavy chain variable region CDR2 comprising SEQ ID NO;

30;

(c) a heavy chain variable region CDR3 comprising SEQ ID NO;

31;

(d) a light chain variable region CDR1 comprising SEQ ID NO;

35;

(e) a light chain variable region CDR2 comprising SEQ ID NO;

36; and

(f) a light chain variable region CDR3 comprising SEQ ID NO;

37.

3. The method of claim 1, which induces or enhances an immune response against an antigen in the subject.

4. The method of claim 1, which induces or enhances a T cell-mediated immune response in the subject.

5. The method of claim 1, wherein the antibody is a human antibody or a chimeric antibody.

6. The method of claim 1, wherein the antibody is selected from the group consisting of an IgG1, an IgG2, an IgG3, an IgG4, an IgM, an IgA1, an IgA2, an IgAsec, an IgD, and an IgE antibody.

7. The method of claim 1, wherein the antigen is selected from the group consisting of a component of a pathogen, a tumor antigen, an allergen and an autoantigen.

8. The method of claim 1, wherein the tumor antigen is selected from the group consisting of β

hCG, gp100 or Pmel17, HER2/neu, WT1, mesothelin, CEA, gp100, MART1, TRP-2, NY-BR-1, NY-CO-58, MN (gp250), idiotype, Tyrosinase, Telomerase, SSX2, MUC-1, MART1, melan-A, NY-ESO-1, MAGE-1, MAGE-3, MAGE-A3, and high molecular weight-melanoma associated antigen (HMW-MAA).

9. The method of claim 1, wherein the antigen is from HIV, HPV, HBV or HCV.

10. The method of claim 1, further comprising administering a therapeutic agent selected from the group consisting of a cytotoxic agent, an immunosuppressive agent, and a chemotherapeutic agent.

11. The method of claim 1, further comprising administering a TLR3 agonist.

12. The method of claim 11, wherein the TLR3 agonist is PolyIC:

LC.

13. The method of claim 1, further comprising administering a TLR7 or TLR8 agonist.

14. The method of claim 13, wherein the TLR7 or TLR8 agonist is resiquimod.

15. The method of claim 1, further comprising administering a cytokine to the subject.

16. The method of claim 15, wherein the cytokine is G-CSF or GM-CSF.

17. A method for targeting an antigen to human DEC-205 in a human subject comprising administering to the human subject an antibody linked to an antigen, wherein the antibody comprises heavy and light chain variable regions selected from the group consisting of:

(a) heavy and light chain variable regions comprising SEQ ID NOs;

28 and 34, respectively, or heavy and light chain variable regions encoded by nucleic acid sequences comprising SEQ ID NOs;

26 and 32, respectively;

(b) heavy and light chain variable regions comprising SEQ ID NOs;

4 and 10, respectively, or heavy and light chain variable regions encoded by nucleic acid sequences comprising SEQ ID NOs;

2 and 8, respectively;

(c) heavy and light chain variable regions comprising SEQ ID NOs;

16 and 22, respectively, or heavy and light chain variable regions encoded by nucleic acid sequences comprising SEQ ID NOs;

14 and 20, respectively;

(d) heavy and light chain variable regions comprising SEQ ID NOs;

40 and 46, respectively, or heavy and light chain variable regions encoded by nucleic acid sequences comprising SEQ ID NOs;

38 and 44, respectively;

(e) heavy and light chain variable regions comprising SEQ ID NOs;

52 and 58, respectively, or heavy and light chain variable regions encoded by nucleic acid sequences comprising SEQ ID NOs;

50 and 56, respectively; and

(f) heavy and light chain variable regions comprising SEQ ID NOs;

76 and 82, respectively, or heavy and light chain variable regions encoded by nucleic acid sequences comprising SEQ ID NOs;

74 and 80, respectively, and

wherein the antibody binds to human DEC-205 comprising SEQ ID NO;

1.

18. The method of claim 17, wherein the antibody comprises heavy and light chain variable regions comprising SEQ ID NOs:

28 and 34, respectively.

19. The method of claim 17, wherein the antibody comprises heavy and light chain variable regions encoded by nucleic acid sequences comprising SEQ ID NOs:

26 and 32, respectively.