IL-17 binding proteins

• US 9,481,736 B2
• Filed: 04/28/2014
• Issued: 11/01/2016
• Est. Priority Date: 03/05/2009
• Status: Active Grant

• Current Assignee: Abbvie Incorporated
• Original Assignee: Abbvie Incorporated
• Inventors: Hsieh, Chung-Ming, Hugunin, Margaret, Murtaza, Anwar, McRae, Bradford L., Kutskova, Yuliya, Memmott, John E., Perez, Jennifer M., Zhong, Suju, Tarcsa, Edit, Clabbers, Anca, Wallace, Craig, Bryant, Shaughn H., Leddy, Mary R.
• Primary Examiner(s): Duffy, Brad
• Assistant Examiner(s): Moseley, II, Nelson B
• Application Number:
  US14/263,724
• Publication Number:
  US 20140356909A1
• Time in Patent Office: 918 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• 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 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• 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 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 21/02 : Muscle relaxants, e.g. for tetanus or cramps
• 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 25/06 : Antimigraine agents
• CPC Class Codes: A61P 25/14 : for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• 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 3/10 : 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 31/16 : for influenza or rhinoviruses
• CPC Class Codes: A61P 33/06 : Antimalarials
• 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 37/06 : 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 5/18 : of the parathyroid hormones
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/06 : Antiarrhythmics
• 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 16/241 : Tumor Necrosis Factors
• CPC Class Codes: C07K 16/244 : Interleukins [IL]
• CPC Class Codes: C07K 16/468 : Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
• CPC Class Codes: C07K 2317/21 : from primates, e.g. man
• CPC Class Codes: C07K 2317/31 : multispecific
• CPC Class Codes: C07K 2317/50 : characterized by immunoglobulin fragments
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/64 : comprising a combination of variable region and constant region components
• 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: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Proteins that bind IL-17 and/or IL-17F are described along with their use in composition and methods for treating, preventing, and diagnosing IL-17 related diseases and for detecting IL-17 in cells, tissues, samples, and compositions.

Claims

1. A method for generating a DVD-Ig binding protein capable of binding two antigens comprising the steps of

a) obtaining a first parent antibody or antigen binding portion thereof, capable of binding TNF-α

;

b) obtaining a second parent antibody or antigen binding portion thereof, capable of binding human IL-17;

c) constructing first and third polypeptide chains comprising VD1-(X1)n-VD2-C-(X2)n, wherein

VD1 is a first heavy chain variable domain obtained from the first parent antibody or antigen binding portion thereof;

VD2 is a second heavy chain variable domain obtained from the second parent antibody or antigen binding portion thereof;

C is a heavy chain constant domain;

X1 is a linker with the proviso that it is not CH1;

X2 is an Fc region; and

n is 0 or 1; and

d) constructing second and fourth polypeptide chains comprising VD1-(X1)n-VD2-C-(X2)n, wherein

VD1 is a first light chain variable domain obtained from the first parent antibody or antigen binding portion thereof;

VD2 is a second light chain variable domain obtained from the second parent antibody or antigen binding thereof;

C is a light chain constant domain;

X1 is a linker with the proviso that it is not CH1;

X2 does not comprise an Fc region; and

n is 0 or 1; and

e) expressing the first, second, third and fourth polypeptide chains;

such that a DVD-Ig binding protein capable of binding TNF-α and

human IL-17 is generated, wherein the binding protein is capable of binding TNF-α and

human IL-17;

wherein, in the first and third polypeptide chains, the VD1 and VD2 heavy chain variable domains comprise an amino acid sequence selected from the group consisting of SEQ ID NOs;

565, 670, 720, 740, 845, and 875; and

wherein in the second and fourth polypeptide chains, the VD1 or VD2 light chain variable domains comprise an amino acid sequence selected from the group consisting of SEQ ID NOs;

570, 675, 725, 745, 850, and 880.

2. The method of claim 1, wherein the first parent antibody or antigen binding portion thereof possesses at least one desired property exhibited by the DVD-Ig binding protein.

3. The method of claim 1, wherein the second parent antibody or antigen binding portion thereof possesses at least one desired property exhibited by the DVD-Ig binding protein.

4. The method of claim 2, wherein the desired property is selected from one or more antibody parameters.

5. The method of claim 3, wherein the desired property is selected from one or more antibody parameters.

6. The method of claim 4, wherein the antibody parameters are selected from the group consisting of antigen specificity, affinity to antigen, potency, biological function, epitope recognition, stability, solubility, production efficiency, immunogenicity, pharmacokinetics, bioavailability, tissue cross reactivity, and orthologous antigen binding.

7. The method of claim 5, wherein the antibody parameters are selected from the group consisting of antigen specificity, affinity to antigen, potency, biological function, epitope recognition, stability, solubility, production efficiency, immunogenicity, pharmacokinetics, bioavailability, tissue cross reactivity, and orthologous antigen binding.

8. The method of claim 1, wherein the first parent antibody or antigen binding portion thereof, binds the first antigen with a different affinity than the affinity with which the second parent antibody or antigen binding portion thereof, binds the second antigen.

9. The method of claim 1, wherein the first parent antibody or antigen binding portion thereof, binds the first antigen with a different potency than the potency with which the second parent antibody or antigen binding portion thereof, binds the second antigen.

10. The method of claim 1, wherein the X1 in the heavy chain domain or light chain domain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:

887-918.

11. The method of claim 1, wherein the other of the VD1 or VD2 heavy chain variable domain comprises an amino acid sequence of a variable heavy region (VH) of an anti-TNF-alpha antibody wherein the amino acid sequence comprises the amino acid sequence of SEQ ID NO:

668.

12. The method of claim 1, wherein the first polypeptide chain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:

562, 572, 667, 677, 687, 697, 707, 717, 727, 737, 842, 852, 862, 872, and 882.

13. The method of claim 1, wherein the other of the VD1 or VD2 light chain variable domain comprises an amino acid sequence of a variable light region (VL) of an anti-TNF-alpha antibody wherein the amino acid sequence comprises the amino acid sequence of SEQ ID NO:

673.

14. The method of claim 1, wherein the second polypeptide chain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:

567, 672, 682, 692, 702, 712, 722, 732, 742, 847, 857, 867, and 877.

15. The method of claim 1, wherein the heavy chain constant domain comprises a CH domain having the amino acid sequence of SEQ ID NO:

671.

16. The method of claim 1, wherein the light chain constant domain comprises a CL domain having the amino acid sequence of SEQ ID NO:

676.

17. The method of claim 1, wherein the VD1 heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:

668, and the VD1 light chain variable domain comprises the amino acid sequence of SEQ ID NO;

673.

18. The method of claim 1, wherein the VD2 heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:

670 and the VD2 light chain variable domain comprises the amino acid sequence of SEQ ID NO;

675.

19. The method of claim 1, wherein the VD2 heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:

670, the VD2 light chain variable domain comprises the amino acid sequence of SEQ ID NO;

675, the VD1 heavy chain variable domain comprises the amino acid sequence of SEQ ID NO;

668, and the VD1light chain variable domain comprises the amino acid sequence of SEQ ID NO;

673.

20. The method of claim 1, wherein the VD1 heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:

670, the VD1 light chain variable domain comprises the amino acid sequence of SEQ ID NO;

675, the VD2 heavy chain variable domain comprises the amino acid sequence of SEQ ID NO;

668, and the VD2light chain variable domain comprises the amino acid sequence of SEQ ID NO;

673.

21. The method of claim 1, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:

667.

22. The method of claim 1, wherein the X1 in the light chain domain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:

887-918.

23. The method of claim 22, wherein the X1 comprises the amino acid sequence of SEQ ID NO:

887.

24. The method of claim 22, wherein the X1 comprises the amino acid sequence of SEQ ID NO:

888.

25. The method of claim 22, wherein the heavy chain constant domain comprises a CH domain of SEQ ID NO:

671.

26. The method of claim 22, wherein the light chain constant domain comprises a CL domain of SEQ ID NO:

676.

27. The method of claim 1, wherein the VD1 heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:

668, the X1 in the heavy chain domain comprises the amino acid sequence of SEQ ID NO;

889, the VD2 heavy chain variable domain comprises the amino acid sequence of SEQ ID NO;

670, the heavy chain constant domain comprises a CH domain of SEQ ID NO;

671, the VD1 light chain variable domain comprises the amino acid sequence of SEQ ID NO;

673, the X1 in the light chain domain comprises the amino acid sequence of SEQ ID NO;

887, the VD2light chain variable domain comprises the amino acid sequence of SEQ ID NO;

675, and wherein the light chain constant domain comprises a CL domain of SEQ ID NO;

676.

28. The method of claim 1, wherein the VD1 heavy chain variable domain comprises the amino acid sequence of SEQ ID NO:

668, the X1 in the heavy chain domain comprises the amino acid sequence of SEQ ID NO;

889, the VD2 heavy chain variable domain comprises the amino acid sequence of SEQ ID NO;

670, the heavy chain constant domain comprises a CH domain of SEQ ID NO;

671, the VD1 light chain variable domain comprises the amino acid sequence of SEQ ID NO;

673, the X1 in the light chain domain comprises the amino acid sequence of SEQ ID NO;

888, the VD2light chain variable domain comprises the amino acid sequence of SEQ ID NO;

675, and wherein the light chain constant domain comprises a CL domain of SEQ ID NO;

676.

29. A method for generating a DVD-Ig binding protein capable of binding two antigens comprising the steps of

a) obtaining a first parent antibody or antigen binding portion thereof, capable of binding TNF-α

;

b) obtaining a second parent antibody or antigen binding portion thereof, capable of binding human IL-17;

c) constructing first and third polypeptide chains comprising VD1-(X1)n-VD2-C-(X2)n, wherein

VD1 is a first heavy chain variable domain obtained from the first parent antibody or antigen binding portion thereof;

VD2 is a second heavy chain variable domain obtained from the second parent antibody or antigen binding portion thereof;

C is a heavy chain constant domain;

X1 is a linker with the proviso that it is not CH1;

X2 is an Fc region; and

n is 0 or 1; and

d) constructing second and fourth polypeptide chains comprising VD1-(X1)n-VD2-C-(X2)n, wherein

VD1 is a first light chain variable domain obtained from the first parent antibody or antigen binding portion thereof;

VD2 is a second light chain variable domain obtained from the second parent antibody or antigen binding thereof;

C is a light chain constant domain;

X1 is a linker with the proviso that it is not CH1;

X2 does not comprise an Fc region; and

n is 0 or 1; and

e) expressing the first, second, third and fourth polypeptide chains;

wherein the binding protein is capable of binding human IL-17 and TNF-α

; and

wherein, in the first and third polypeptide chains, the VD1 or VD2 heavy chain variable domain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs;

565, 670, 720, 740, 845, and 875.

30. The method of claim 29, wherein the X1 in the polypeptide chain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:

887-918.

31. The method of claim 30, wherein the polypeptide chain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:

562, 572, 667, 677, 687, 697, 707, 717, 727, 737, 842, 852, 862, 872, and 882.

32. The method of claim 30, wherein the polypeptide chain comprises the amino acid sequence of SEQ ID NO:

667.

33. The method of claim 32, wherein the heavy chain constant domain comprises a CH domain of SEQ ID NO:

671.

34. A method for generating a DVD-Ig binding protein capable of binding two antigens comprising the steps of

a) obtaining a first parent antibody or antigen binding portion thereof, capable of binding TNF-α

;

b) obtaining a second parent antibody or antigen binding portion thereof, capable of binding human IL-17;

c) constructing first and third polypeptide chains comprising VD1-(X1)n-VD2-C-(X2)n, wherein

VD1 is a first heavy chain variable domain obtained from the first parent antibody or antigen binding portion thereof;

VD2 is a second heavy chain variable domain obtained from the second parent antibody or antigen binding portion thereof;

C is a heavy chain constant domain;

X1 is a linker with the proviso that it is not CH1;

X2 is an Fc region; and

n is 0 or 1; and

d) constructing second and fourth polypeptide chains comprising VD1-(X1)n-VD2-C-(X2)n, wherein

VD1 is a first light chain variable domain obtained from the first parent antibody or antigen binding portion thereof;

VD2 is a second light chain variable domain obtained from the second parent antibody or antigen binding thereof;

C is a light chain constant domain;

X1 is a linker with the proviso that it is not CH1;

X2 does not comprise an Fc region; and

n is 0 or 1; and

e) expressing the first, second, third and fourth polypeptide chains;

wherein the binding protein is capable of binding human IL-17 and TNF-α

; and

wherein, in the second and fourth polypeptide chains, the VD1 or VD2 light chain variable domain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs;

570, 675, 725, 745, 850, and 880.

35. The binding protein of claim 34, wherein the X1 in the polypeptide chain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:

887-918.

36. The method of claim 35, wherein the light chain constant domain comprises a CL domain of SEQ ID NO:

676.