US 11,530,262 B2 · Interleukin-31 monoclonal antibodies for veterinary use

Abstract

A monoclonal antibody, or antigen-binding portion thereof is provided that specifically binds to a region on a mammalian IL-31 protein involved with interaction of the IL-31 protein with its co-receptor, wherein the binding of said antibody to said region is impacted by mutations in a 15H05 epitope binding region selected from: a region between about amino acid residues 124 and 135 of a feline IL-31 sequence represented by SEQ ID NO: 157 (Feline_IL31_wildtype); a region between about amino acid residues 124 and 135 of a canine IL-31 sequence represented by SEQ ID NO: 155 (Canine_IL31); and a region between about amino acid residues 118 and 129 of an equine IL-31 sequence represented by SEQ ID NO: 165 (Equine_IL31). Such antibodies can be in the form of veterinary compositions useful for treating IL-31-mediated disorders in cats, dogs, or horses.

A composition comprising an anti-IL31 antibody, wherein said antibody comprises:

(1) a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
13, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:14, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
15, a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
16, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
17, and a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:18;
(2) a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
19, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
20, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
21, a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
22, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
23, and a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
24;
(3) a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
25, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
26, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
27, a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
28, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
29, and a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
30;
(4) a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
31, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
32, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
33, a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
34, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
35, and a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
36;
(5) a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
37, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
38, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
39, a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
40, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
41, and a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
42;
(6) a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
43, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
44, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
45, a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
46, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
47, and a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
48;
(7) a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
49, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
50, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
51, a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
52, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
53, and a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
54;
(8) a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
55, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
56, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
57, a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
58, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
59, and a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
60;
(9) a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
61, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
62, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
63, a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
64, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
65, and a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
66);
(10) a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
200, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
201, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
202, a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
203, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
204, and a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
205;
or
(11) a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
206, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
207, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
208, a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO:
209, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:
210, and a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
211.

73 more elements

Description48,901 words

Summary6,326 words

#The present invention relates to the field of recombinant monoclonal antibodies and their uses in clinical and scientific procedures, including diagnostic procedures. The present invention also provides isolated anti-IL31 antibodies in the form of veterinary compositions useful for treating an IL-31-mediated disorder in a mammal, such as a cat, dog, or horse.

#Atopic dermatitis has been defined by the American College of Veterinary Dermatology task force as “a genetically-predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features” (Olivry, et al. Veterinary Immunology and Immunopathology 2001; 81: 143-146). The task force also recognized that the disease in canines has been associated with allergen-specific IgE (Olivry, et al. 2001 supra; Marsella & Olivry Clinics in Dermatology 2003; 21: 122-133). Severe pruritus, along with secondary alopecia and erythema, are the most noticeable and concerning symptoms to pet owners.

#The potential factors involved in allergic dermatitis are numerous and poorly understood. Components in food may trigger atopic dermatitis (Picco, et al. Vet Dermatol. 2008; 19: 150-155), as well as environmental allergens such as fleas, dust mites, ragweed, plant extracts, etc. Genetic factors also play an important role. Although there is no confirmed breed predilection, some mode of inheritance is thought to increase predisposition to atopic dermatitis (Sousa & Marsella Veterinary Immunology and Immunopathology 2001; 81: 153-157; Schwartzman, et al. Clin. Exp. Immunol. 1971; 9: 549-569).

Brief description of the drawings26 figures

#FIG. 1A is an alignment showing amino acid sequence conservation between IL-31 from different species. In particular, a comparison between SEQ ID NO: 155 (canine IL-31), SEQ ID NO: 157 (feline IL-31), SEQ ID NO: 165 (equine IL-31), and SEQ ID NO: 181 (human IL-31) is shown. In FIG. 1B, the percent amino acid sequence identity between canine, feline, horse and human IL-31 is also indicated.

#FIG. 2 details the affinity with which candidate antibodies with CDRs derived from mouse origin bind feline and canine IL-31 using surface plasmon resonance (SPR) on a Biacore system (Biacore Life Sciences (GE Healthcare), Uppsala, Sweden).

#FIG. 3 is a table showing potency (1050 (μg/ml)) of candidate antibodies with CDRs derived from mouse origin as measured by canine and feline cellular assays. In particular, the candidate antibodies were assessed for their ability to inhibit IL-31-mediated STAT phosphorylation in canine DH-82 or feline FCWF4 macrophage-like cells.

Detailed description40,091 words

#Antibodies described in FIGS. 12, 13A and 13B, and 14A and 14B were grown in culture conditions equivalent to culture condition A from FIG. 17C.

#SEQ ID NO: 1 is a variable heavy chain CDR1 referred to herein as MU_15H05_VH_CDR1;

#SEQ ID NO: 2 is a variable heavy chain CDR2 referred to herein as MU_15H05_VH_CDR2;

Facts

Application

16/256,223Filed 24 Jan 2019 · us provisional application

Priority

16 Mar 2018

Published

US 2019/0284272 A119 Sep 2019

Granted

20 Dec 2022

Term ends

21 Feb 2039

Estimated · how

20 years from earliest known nonprovisional domestic filing plus recorded patent term adjustment, including 28 days of adjustment. Maintenance-fee lapses, terminal disclaimers and statutory extensions have not been checked. The continuity chain may be incomplete; this is not an enforceability determination.

Classification17 codes

C07K 16/244
Against cytokines, lymphokines or interferons: interleukins [IL]
A61P 17/00
Drugs for dermatological disorders
A61P 35/00
Antineoplastic agents
A61P 37/00
Drugs for immunological or allergic disorders

Timeline

16 Mar 2018Priority claimedParent application 62/643,940
24 Jan 2019Application filedUS 16/256,223
28 Mar 2019Assigned to Zoetis Services LLCassignment of assignor's interest
19 Sep 2019PublishedUS 2019/0284272 A1
20 Dec 2022GrantedUS 11,530,262 B2
12 Oct 2026TodayWithin its term
21 Feb 2039Term endsEstimated, includes 28 days of adjustment

Interleukin-31 monoclonal antibodies for veterinary use

Life of this patent

Interleukin-31 monoclonal antibodies for veterinary use

Life of this patent

Life of this patent

Abstract

Drawings

Drawings

Claims5

Description48,901 words

Drawings

Classification17 codes

Life of this patent

Description48,901 words