Monoclonal antibodies to dendritic cells

• US 9,095,626 B2
• Filed: 02/15/2012
• Issued: 08/04/2015
• Est. Priority Date: 05/08/2000
• Status: Expired due to Fees

• Current Assignee: Celldex Therapeutics Incorporated
• Original Assignee: Celldex Therapeutics Incorporated
• Inventors: Deo, Yashwant M., Keler, Tibor, Treml, John, Endres, Michael
• Primary Examiner(s): Ewoldt, Gerald R
• Application Number:
  US13/397,476
• Publication Number:
  US 20120148596A1
• Time in Patent Office: 1,266 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A01K 2267/01 Animal expressing industrially exogenous proteins
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/6056 Antibodies
• CPC Class Codes: A61K 2239/31 characterized by the route of administration
• CPC Class Codes: A61K 39/08 Clostridium, e.g. Clostridium tetani
• CPC Class Codes: A61K 39/4615 Dendritic cells
• CPC Class Codes: A61K 39/4622 Antigen presenting cells
• CPC Class Codes: A61K 39/4644 Cancer antigens
• CPC Class Codes: A61K 47/646 the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• 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 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/33 from Clostridium (G)
• CPC Class Codes: C07K 14/473 : alpha-Glycoproteins
• CPC Class Codes: C07K 14/705 : Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 16/18 : against material from animals or humans
• CPC Class Codes: C07K 16/28 : against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/2851 : against the lectin superfamily, e.g. CD23, CD72
• CPC Class Codes: C07K 16/46 : Hybrid immunoglobulins hybrids of an immunoglobulin with a peptide not being an immunoglobulin C07K19/00
• CPC Class Codes: C07K 2317/21 : from primates, e.g. man
• CPC Class Codes: C07K 2317/54 : F(ab')2
• CPC Class Codes: C07K 2317/56 : variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/622 : Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/77 : Internalization into the cell
• CPC Class Codes: C07K 2319/00 : Fusion polypeptide
• CPC Class Codes: C07K 2319/30 : Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 2319/33 : fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
• CPC Class Codes: C07K 2319/55 : containing a fusion with a toxin, e.g. diphteria toxin

Abstract

Isolated human monoclonal antibodies and antigen-binding portions thereof which specifically bind to dendritic cells are disclosed. Also disclosed are bispecifics, immunotoxins and antigen conjugates which include the antibodies or antibody portions. The human antibodies can be produced in a non-human transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoing V-D-J recombination and isotype switching. Also disclosed are pharmaceutical compositions comprising the human antibodies, non-human transgenic animals and hybridomas which produce the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.

Claims

1. An isolated monoclonal antibody that binds to the human macrophage mannose receptor and comprises heavy and light chain variable regions, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:

4 .

8. A composition comprising the antibody of claim 1 and a carrier.

9. The composition of claim 8, further comprising an adjuvant.

2. An isolated monoclonal antibody that binds to the human macrophage mannose receptor and comprises heavy and light chain variable regions, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:

2.

10. A composition comprising the antibody of claim 2 and a carrier.

11. The composition of claim 10, further comprising an adjuvant.

3. An isolated monoclonal antibody comprising a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:

4 and a light chain variable region comprising the amino acid sequence shown in SEQ ID NO;

2.

14. A composition comprising the antibody of claim 3 and a carrier.

15. The composition of claim 14, further comprising an adjuvant.

4. An isolated monoclonal antibody that binds to the human macrophage mannose receptor and comprises heavy and light chain variable regions, wherein:

(a) the heavy chain variable region is encoded by the nucleotide sequence shown in SEQ ID NO;

3;

(b) the light chain variable region is encoded by the nucleotide sequence shown in SEQ ID NO;

1;

or

(c) the heavy variable region is encoded by the nucleotide sequence shown in SEQ ID NO;

3 and the light variable region is encoded by the nucleotide sequence shown in SEQ ID NO;

1.

12. A composition comprising the antibody of claim 4 and a carrier.

13. The composition of claim 12, further comprising an adjuvant.

5. An isolated monoclonal antibody comprising a heavy chain variable region comprising CDR1, CDR2, and CDR3 sequences and a light chain variable region comprising CDR1, CDR2, and CDR3 sequences, wherein:

(a) the heavy chain variable region CDR3 sequence comprises amino acid residues 99-105 of SEQ ID NO;

4;

(b) the light chain variable region CDR3 sequence comprises amino acid residues 89-97 of SEQ ID NO;

2;

(c) the heavy chain variable region CDR2 sequence comprises amino acid residues 50-66 of SEQ ID NO;

4;

(d) the light chain variable region CDR2 sequence comprises amino acid residues 50-56 of SEQ ID NO;

2;

(e) the heavy chain variable region CDR1 sequence comprises amino acid residues 31-35 of SEQ ID NO;

4; and

(f) the light chain variable region CDR 1 sequence comprises amino acid residues 24-34 of SEQ ID NO;

2.

6. A composition comprising the antibody of claim 5 and a carrier.

7. The composition of claim 6, further comprising an adjuvant.