Nucleic acid molecules encoding humanized antibody molecules specific for IL-31

• US 8,685,669 B2
• Filed: 06/03/2013
• Issued: 04/01/2014
• Est. Priority Date: 12/07/2007
• Status: Active Grant

• Current Assignee: Zymogenetics Incorporated (Bristol-Myers Squibb Company), Merck Serono SA (Merck & Co., Inc.)
• Original Assignee: Zymogenetics Incorporated (Bristol-Myers Squibb Company), Merck Serono SA (Merck & Co., Inc.)
• Inventors: Bondensgaard, Kent, Beckmann, Roland
• Primary Examiner(s): KEMMERER, ELIZABETH
• Application Number:
  US13/908,436
• Publication Number:
  US 20130295611A1
• Time in Patent Office: 302 Days
• Field of Search: None
• US Class Current: 435/69.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• 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 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: C07K 16/244 Interleukins [IL]
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/51 Complete heavy chain or Fd fragment, i.e. VH + CH1
• CPC Class Codes: C07K 2317/515 Complete light chain, i.e. VL + CL
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• 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: C12N 15/63 Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
• CPC Class Codes: C12N 5/10 Cells modified by introduction of foreign genetic material

Abstract

The invention provides humanized mouse anti-human IL-31 antibodies and antibody fragments that are capable of binding IL-31 and thereby neutralizing, inhibiting, limiting, or reducing the proinflammatory or pro-pruritic effects of IL-31.

Claims

1. An isolated nucleic acid molecule encoding a humanized monoclonal antibody that specifically binds to human IL-31, wherein the encoded humanized monoclonal antibody comprises a humanized heavy chain variable domain and a humanized light chain variable domain, wherein the humanized heavy chain variable domain and the humanized light chain variable domain each comprises a complementarity determining region (CDR) and a framework region (FR), wherein the humanized heavy chain variable domain complementarity determining region comprises:

a) a CDR1 having the amino acid residues of SEQ ID NO;

1;

b) a CDR2 having the amino acid residues of SEQ ID NO;

2; and

c) a CDR3 having the amino acid residues of SEQ ID NO;

3;

wherein the humanized heavy chain variable domain framework region comprises;

d) a FR1 having the amino acid residues of SEQ ID NO;

12;

e) a FR2 having the amino acid residues of SEQ ID NO;

13;

f) a FR3 having the amino acid residues of SEQ ID NO;

14; and

g) a FR4 having the amino acid residues of SEQ ID NO;

15;

wherein the humanized light chain variable domain complementarity determining region comprises;

h) a CDR1 having the amino acid residues of SEQ ID NO;

5;

i) a CDR2 having the amino acid residues of SEQ ID NO;

6; and

j) a CDR3 having the amino acid residues of SEQ ID NO;

7; and

wherein the humanized light chain variable domain framework region comprises;

k) a FR5 having the amino acid residues of SEQ ID NO;

17;

l) a FR6 having the amino acid residues of SEQ ID NO;

18;

m) a FR7 having the amino acid residues of SEQ ID NO;

19; and

n) a FR8 having the amino acid residues of SEQ ID NO;

20.

2. The isolated nucleic acid molecule of claim 1, wherein the nucleic acid molecule further encodes a human immunoglobulin constant domain.

3. The isolated nucleic acid molecule of claim 2, wherein the human immunoglobulin constant domain is IgG1, IgG2, IgG3 or IgG4.

4. The isolated nucleic acid molecule of claim 2, wherein the human immunoglobulin constant domain is IgG4.

5. An expression vector comprising the following operably linked elements:

a) a transcription promoter;

b) the nucleic acid molecule of claim 1; and

c) a transcription terminator.

6. An expression vector comprising the following operably linked elements:

a) a first transcription promoter;

b) a first nucleic acid molecule encoding the humanized heavy chain variable domain of claim 1;

c) a first transcription terminator;

d) a second transcription promoter;

e) a second nucleic acid molecule encoding the humanized light chain variable domain of claim 1; and

f) a second transcription terminator.

7. An expression vector comprising the following operably linked elements:

a) a first transcription promoter;

b) a first nucleic acid molecule encoding the humanized heavy chain variable domain of claim 1;

c) a first transcription terminator;

d) the first transcription promoter;

e) a second nucleic acid molecule encoding the humanized light chain variable domain of claim 1; and

f) a second transcription terminator.

8. A recombinant host cell comprising the expression vector of claim 5.

9. A recombinant host cell comprising the expression vector of claim 6.

10. A recombinant host cell comprising the expression vector of claim 7.

11. A recombinant host cell comprising:

a) a first expression vector comprising;

i) a first transcription promoter;

ii) a first nucleic acid molecule encoding the humanized heavy chain variable domain of claim 1; and

iii) a first transcription terminator; and

b) a second expression vector comprising;

i) a second transcription promoter;

ii) a second nucleic acid molecule encoding the humanized light chain variable domain of claim 1; and

iii) a second transcription terminator.

12. A method of producing the humanized IL-31 monoclonal antibody encoded by the nucleic acid molecule in the expression vector of claim 5 comprising:

a) culturing a host cell comprising said vector under conditions wherein the monoclonal antibody is expressed; and

b) recovering the monoclonal antibody.

13. A method of producing the humanized IL-31 monoclonal antibody encoded by the nucleic acid molecule in the expression vector of claim 6 comprising:

a) culturing a host cell comprising said vector under conditions wherein the monoclonal antibody is expressed; and

b) recovering the monoclonal antibody.

14. A method of producing the humanized IL-31 monoclonal antibody encoded by the nucleic acid molecule in the expression vector of claim 7 comprising:

a) culturing a host cell comprising said vector under conditions wherein the monoclonal antibody is expressed; and

b) recovering the monoclonal antibody.

15. A method of producing a humanized IL-31 monoclonal antibody comprising:

a) culturing the host cell of claim 11 under conditions wherein the humanized heavy and light chain variable domains are expressed; and

b) recovering the monoclonal antibody.