Dual specific binding proteins directed against IL-13 and IL-17

• US 9,120,870 B2
• Filed: 12/28/2012
• Issued: 09/01/2015
• Est. Priority Date: 12/30/2011
• Status: Active Grant

• Current Assignee: Abbvie Incorporated
• Original Assignee: Abbvie Incorporated
• Inventors: Hsieh, Chung-Ming, Ghayur, Tariq, Goodreau, Carrie L.
• Primary Examiner(s): Jiang, Dong
• Application Number:
  US13/729,645
• Publication Number:
  US 20130236458A1
• Time in Patent Office: 977 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• 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 17/10 Anti-acne agents
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis
• 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 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 25/18 : Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 : Antidepressants
• 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 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• 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 33/00 : Antiparasitic agents
• 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 37/04 : 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 39/00 : General protective or antinoxious agents
• 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 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• 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: A61P 9/12 : Antihypertensives
• 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 2317/14 : Specific host cells or culture conditions, e.g. components, pH or temperature
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/31 : multispecific
• 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 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/567 : Framework region [FR]
• 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: G01N 2333/54 : Interleukins [IL]
• CPC Class Codes: G01N 2333/5437 : IL-13
• CPC Class Codes: G01N 33/6854 : Immunoglobulins
• CPC Class Codes: G01N 33/6869 : Interleukin

Abstract

Engineered multivalent and multispecific binding proteins that bind IL-13 and/or IL-17 are provided, along with methods of making and uses in the prevention, diagnosis, and/or treatment of disease.

Claims

1. A binding protein comprising first and second polypeptide chains, each independently comprising VD1-(X1)n-VD2-C-(X2)n, wherein

VD1 is a first antibody variable domain;

VD2 is a second antibody variable domain;

C is an antibody constant domain;

X1 is a linker;

X2 is an antibody Fc region; and

n is 0 or 1;

wherein the VD1 domains on the first and second polypeptide chains form a first functional target binding site and the VD2 domains on the first and second polypeptide chains form a second functional target binding site, and wherein the binding protein binds IL-13 and IL-17, wherein

(a) the variable domains that form a functional target binding site for IL-13 comprise the amino acid sequences of SEQ ID NO;

32 and SEQ ID NO;

33, and

(b) the variable domains that form a functional target binding site for IL-17 comprise the amino acid sequences of

SEQ ID NO;

36 and SEQ ID NO;

37,

SEQ ID NO;

38 and SEQ ID NO;

39,

SEQ ID NO;

40 and SEQ ID NO;

41,

SEQ ID NO;

42 and SEQ ID NO;

52,

SEQ ID NO;

42 and SEQ ID NO;

53,

SEQ ID NO;

43 and SEQ ID NO;

50,

SEQ ID NO;

44 and SEQ ID NO;

51,

SEQ ID NO;

45 and SEQ ID NO;

54,

SEQ ID NO;

46 and SEQ ID NO;

51,

SEQ ID NO;

47 and SEQ ID NO;

54,

SEQ ID NO;

48 and SEQ ID NO;

51, or

SEQ ID NO;

49 and SEQ ID NO;

51.

2. The binding protein according to claim 1, wherein the first polypeptide chain comprises a first VD1-(X1)n-VD2-C-(X2)n, wherein

VD1 is a first antibody heavy chain variable domain;

VD2 is a second antibody heavy chain variable domain;

C is an antibody heavy chain constant domain;

X1 is a linker;

X2 is an antibody Fc region; and

n is 0 or 1,

wherein the second polypeptide chain comprises a second VD1-(X1)n-VD2-C, wherein

VD1 is a first antibody light chain variable domain;

VD2 is a second antibody light chain variable domain;

C is an antibody light chain constant domain;

X1 is a linker;

n is 1 for (X1)n; and

n is 0 for (X2)n,

wherein the VD1 domains on the first and second polypeptide chains form a first functional target binding site and the VD2 domains on the first and second polypeptide chains form a second functional target binding site.

3. The binding protein according to claim 1, wherein X1 comprises the amino acid sequence of any one of SEQ ID NOs:

1-29 or a G4S (SEQ ID NO;

     29) repeating sequence.

4. The binding protein according to claim 1, wherein the Fc region is a variant sequence Fc region.

5. The binding protein according to claim 1, wherein the Fc region is an Fc region from IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgE, or IgD.

6. The binding protein according to claim 1, comprising two first polypeptide chains and two second polypeptide chains.

7. A pharmaceutical composition comprising the binding protein according to claim 1 and a pharmaceutically acceptable carrier.

8. The pharmaceutical composition according to claim 7, further comprising at least one additional therapeutic agent.

9. A kit for assaying a test sample for the presence, amount, or concentration of IL13 and/or IL17 in the sample, said kit comprising:

(a) instructions for assaying the test sample for IL13 and/or IL17; and

(b) at least one binding protein according to claim 1.

10. A binding protein conjugate comprising the binding protein according to claim 1 and an immunoadhesion molecule, an imaging agent, a therapeutic agent, or a cytotoxic agent.

11. The binding protein conjugate according to claim 10, wherein the imaging agent is a radiolabel, an enzyme, a fluorescent label, a luminescent label, a bioluminescent label, a magnetic label, or biotin.

12. The binding protein conjugate according to claim 11, wherein said radiolabel is ³H, ¹⁴C, ³⁵S, ⁹⁰Y, ⁹⁹Tc, ¹¹¹In, ¹²⁵I, ¹³¹I, ¹⁷⁷Lu, ¹⁶⁶Ho, or ¹⁵³Sm.

13. The binding protein conjugate according to claim 10, wherein said therapeutic or cytotoxic agent is an anti-metabolite, an alkylating agent, an antibiotic, a growth factor, a cytokine, an anti-angiogenic agent, an anti-mitotic agent, an anthracycline, toxin, or an apoptotic agent.

14. The binding protein according to claim 1, wherein the binding protein is a crystallized binding protein.

15. A binding protein comprising first and second polypeptide chains, each independently comprising VD1-(X1)n-VD2-C-(X2)n, wherein

VD1 is a first antibody variable domain;

VD2 is a second antibody variable domain;

C is an antibody constant domain;

X1 is a linker;

X2 is an antibody Fc region; and

n is 0 or 1;

wherein the VD1 domains on the first and second polypeptide chains form a first functional target binding site and the VD2 domains on the first and second polypeptide chains form a second functional target binding site, and wherein the binding protein binds IL-13 and IL-17, wherein

(a) the variable domains that form a functional target binding site for IL-13 comprise the amino acid sequences of SEQ ID NO;

32 and SEQ ID NO;

33, and

(b) the variable domains that form a functional target binding site for IL-17 comprise an amino acid sequence selected from the group consisting of SEQ ID NOs;

36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, and 54.

16. An IL-13 and IL-17 binding protein, wherein the binding protein comprises the amino acid sequences of any one of:

(a) DVD2166H (comprising SEQ ID NOs;

32 and

     36) and DVD2166L (comprising SEQ ID NOs;

33 and

     37);

(b) DVD2167H (comprising SEQ ID NOs;

36 and

     32) and DVD2167L (comprising SEQ ID NOs;

37 and

     33);

(c) DVD2168H (comprising SEQ ID NOs;

32 and

     36) and DVD2168L (comprising SEQ ID NOs;

33 and

     37);

(d) DVD2169H (comprising SEQ ID NOs;

36 and

     32) and DVD2169L (comprising SEQ ID NOs;

37 and

     33);

(e) DVD2170H (comprising SEQ ID NOs;

32 and

     36) and DVD2170L (comprising SEQ ID NOs;

33 and

     37);

(f) DVD2171H (comprising SEQ ID NOs;

36 and

     32) and DVD2171L (comprising SEQ ID NOs;

37 and

     33);

(g) DVD2172H (comprising SEQ ID NOs;

32 and

     38) and DVD2172L (comprising SEQ ID NOs;

33 and

     39);

(h) DVD2173H (comprising SEQ ID NOs;

38 and

     32) and DVD2173L (comprising SEQ ID NOs;

39 and

     33);

(i) DVD2174H (comprising SEQ ID NOs;

32 and

     38) and DVD2174L (comprising SEQ ID NOs;

33 and

     39);

(j) DVD2175H (comprising SEQ ID NOs;

38 and

     32) and DVD2175L (comprising SEQ ID NOs;

39 and

     33);

(k) DVD2176H (comprising SEQ ID NOs;

32 and

     38) and DVD2176L (comprising SEQ ID NOs;

33 and

     39);

(l) DVD2177H (comprising SEQ ID NOs;

38 and

     32) and DVD2177L (comprising SEQ ID NOs;

39 and

     33);

(m) DVD2178H (comprising SEQ ID NOs;

32 and

     40) and DVD2178L (comprising SEQ ID NOs;

33 and

     41);

(n) DVD2179H (comprising SEQ ID NOs;

40 and

     32) and DVD2179L (comprising SEQ ID NOs;

41 and

     33);

(o) DVD2180H (comprising SEQ ID NOs;

32 and

     40) and DVD2180L (comprising SEQ ID NOs;

33 and

     41);

(p) DVD2181H (comprising SEQ ID NOs;

40 and

     32) and DVD2181L (comprising SEQ ID NOs;

41 and

     33);

(q) DVD2182H (comprising SEQ ID NOs;

32 and

     40) and DVD2182L (comprising SEQ ID NOs;

33 and

     41); and

(r) DVD2183H (comprising SEQ ID NOs;

40 and

     32) and DVD2183L (comprising SEQ ID NOs;

41 and

     33).