IP Library Granted Patent US 8,685,669
Granted Patent B2
US 8,685,669 · App. 13/908,436 · Granted Apr 1, 2014

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

Inventors: Kent Bondensgaard (Vaerlose, DK); Roland Beckmann (Vienna, AT)
Assignees: ZymoGenetics, Inc.; Merck Serono S/A
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Quick Facts
Patent No.
US 8,685,669
App. No.
13/908,436
Granted
Apr 1, 2014
Kind
B2
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 (63)

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.

Continuity (3)
Division 12329820 · Dec 8, 2008
Provisional Application 61012362 · Dec 7, 2007
Related Publication 20130295611A1 · Nov 7, 2013