# US 11,433,139 B2 · Peptide vaccines against interleukin-31

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- Number: US 11,433,139 B2
- Document ID: US11433139B2
- Status: Granted
- Kind: B2
- Application number: 16/356,505
- Filed: 2019-03-18
- Published: 2019-09-19
- Granted: 2022-09-06
- Earliest claimed: 2018-03-16
- Assignees: Zoetis Services LLC
- Applicants: Zoetis Services LLC
- Inventors: Gary Francis Bammert; Steven Alan Dunham
- Web page: https://patentgrep.com/patent/US11433139B2

## CPC

- A61K 47/646: {the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines}
- A61K 38/12: Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)}
- A61K 39/0008: {Antigens related to auto-immune diseases; Preparations to induce self-tolerance}
- A61K 39/00114: {Interleukins [IL]}
- A61K 39/385: Haptens or antigens, bound to carriers
- A61K 47/6415: {Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins}
- A61K 47/642: {the peptide or protein in the drug conjugate being a cytokine, e.g. IL2, chemokine, growth factors or interferons being the inactive part of the conjugate}
- G01N 33/6854: {Immunoglobulins}
- G01N 33/6869: {Interleukin}
- A61K 2039/552: {Veterinary vaccine}
- A61K 2039/55505: {Inorganic adjuvants}
- A61K 2039/577: {tolerising response}
- A61K 2039/6037: {Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

A vaccine composition for immunizing and/or protecting a mammal against an IL-31 mediated disorder is provided, wherein the composition includes: the combination of a carrier polypeptide and at least one mimotope selected from a feline IL-31 mimotope, a canine IL-31 mimotope, a horse IL-31 mimotope, and a human IL-31 mimotope; and an adjuvant. Such vaccines can be in the form of pharmaceutical compositions useful for treating or protecting mammals such as cats, dogs, horses, or humans against IL-31-mediated disorders.

## Claims

### Claim 1

A vaccine composition for immunizing and/or protecting a mammal against an interleukin-31 (IL-31) mediated disorder, wherein said composition comprises:
a) the combination of a carrier polypeptide and at least one IL-31 mimotope, wherein said IL-31 mimotope is:
i) a parent equine IL-31 mimotope which is a peptide from about 5 to about 40 amino acid residues in length and is and/or comprises as part thereof an amino acid sequence selected from the group consisting of SMPTDNFERKRF (SEQ ID NO: 189), NSSAILPYFKAISPSLNNDKSL YIIEQLDKLNF (SEQ ID NO: 194), GPIYQLQPKEIQAIIVELQNLSKK (SEQ ID NO: 198), and KGVQKF (SEQ ID NO: 202); or
ii) a variants IL-31 mimotope which is a peptide from about 5 to about 40 amino acid residues in length that has at least 50% amino acid sequence identity with said parent equine IL-31 mimotope and is and/or comprises the amino acid sequence of said parent equine IL-31 mimotope except for one or more amino acid substitutions within said amino acid sequence, wherein said variant IL-31 mimotope retains anti-IL-31 binding;
and
b) an adjuvant.

### Claim 2 (depends on 1)

The vaccine composition of claim 1, wherein the mimotope binds to an anti-IL31 antibody or antigen-binding portion thereof that specifically binds to a region on a mammalian IL-31 protein involved with interaction of the IL-31 protein with its co-receptor.

### Claim 3 (depends on 2)

The vaccine composition of claim 2, wherein the binding of said antibody to said region is impacted by mutations in a 15H05 epitope binding region between about amino acid residues 118 and 129 of an equine IL-31 sequence represented by SEQ ID NO: 165 (Equine_IL31).

### Claim 4 (depends on 2)

The vaccine composition of claim 2, wherein the mimotope binds to an anti-IL-31 antibody or antigen-binding portion thereof comprising at least one of the following combinations of complementary determining region (CDR) sequences:
1) antibody 15H05: variable heavy (VH)-CDR1 of SYTIH (SEQ ID NO: 1), VH-CDR2 of NINPTSGYTENNQRFKD (SEQ ID NO: 2), VH-CDR3 of WGFKYDGEWSFDV (SEQ ID NO: 3), variable light (VL)-CDR1 of RASQGISIWLS (SEQ ID NO: 4), VL-CDR2 of KASNLHI (SEQ ID NO: 5), and VL-CDR3 of LQSQTYPLT (SEQ ID NO: 6);
2) antibody ZIL1: variable heavy (VH)-CDR1 of SYGMS (SEQ ID NO: 13), VH-CDR2 of HINSGGSSTYYADAVKG (SEQ ID NO:14), VH-CDR3 of VYTTLAAFWTDNFDY (SEQ ID NO: 15), variable light (VL)-CDR1 of SGSTNNIGILAAT (SEQ ID NO: 16), VL-CDR2 of SDGNRPS (SEQ ID NO: 17, and VL-CDR3 of QSFDTTLDAYV (SEQ ID NO:18);
3) antibody ZIL8: VH-CDR1 of DYAMS (SEQ ID NO: 19), VH-CDR2 of GIDSVGSGTSYADAVKG (SEQ ID NO: 20), VH-CDR3 of GFPGSFEH (SEQ ID NO: 21), VL-CDR1 of TGSSSNIGSGYVG (SEQ ID NO: 22), VL-CDR2 of YNSDRPS (SEQ ID NO: 23), VL-CDR3 of SVYDRTFNAV (SEQ ID NO: 24);
4) antibody ZIL9: VH-CDR1 of SYDMT (SEQ ID NO: 25), VH-CDR2 of DVNSGGTGTAYAVAVKG (SEQ ID NO: 26), VH-CDR3 of LGVRDGLSV (SEQ ID NO: 27), VL-CDR1 of SGESLNEYYTQ (SEQ ID NO: 28), VL-CDR2 of RDTERPS (SEQ ID NO: 29), VL-CDR3 of ESAVDTGTLV (SEQ ID NO: 30);
5) antibody ZIL11: VH-CDR1 of TYVMN (SEQ ID NO: 31), VH-CDR2 of SINGGGSSPTYADAVRG (SEQ ID NO: 32), VH-CDR3 of SMVGPFDY (SEQ ID NO: 33), VL-CDR1 of SGESLSNYYAQ (SEQ ID NO: 34), VL-CDR2 of KDTERPS (SEQ ID NO: 35), VL-CDR3 of ESAVSSDTIV (SEQ ID NO: 36);
6) antibody ZIL69: VH-CDR1 of SYAMK (SEQ ID NO: 37), VH-CDR2 of TINNDGTRTGYADAVRG (SEQ ID NO: 38), VH-CDR3 of GNAESGCTGDHCPPY (SEQ ID NO: 39), VL-CDR1 of SGESLNKYYAQ (SEQ ID NO: 40), VL-CDR2 of KDTERPS (SEQ ID NO: 41), VL-CDR3 of ESAVSSETNV (SEQ ID NO: 42);
7) antibody ZIL94: VH-CDR1 of TYFMS (SEQ ID NO: 43), VH-CDR2 of LISSDGSGTYYADAVKG (SEQ ID NO: 44), VH-CDR3 of FWRAFND (SEQ ID NO: 45), VL-CDR1 of GLNSGSVSTSNYPG (SEQ ID NO: 46), VL-CDR2 of DTGSRPS (SEQ ID NO: 47), VL-CDR3 of SLYTDSDILV (SEQ ID NO: 48);
8) antibody ZIL154: VH-CDR1 of DRGMS (SEQ ID NO: 49), VH-CDR2 of YIRYDGSRTDYADAVEG (SEQ ID NO: 50), VH-CDR3 of WDGSSFDY (SEQ ID NO: 51), VL-CDR1 of KASQSLLHSDGNTYLD (SEQ ID NO: 52), VL-CDR2 of KVSNRDP (SEQ ID NO: 53), VL-CDR3 of MQAIHFPLT (SEQ ID NO: 54);
9) antibody ZIL159: VH-CDR1 of SYVMT (SEQ ID NO: 55), VH-CDR2 of GINSEGSRTAYADAVKG (SEQ ID NO: 56), VH-CDR3 of GDIVATGTSY (SEQ ID NO: 57), VL-CDR1 of SGETLNRFYTQ (SEQ ID NO: 58), VL-CDR2 of KDTERPS (SEQ ID NO: 59), VL-CDR3 of KSAVSIDVGV (SEQ ID NO: 60);
10) antibody ZIL171: VH-CDR1 of TYVMN (SEQ ID NO: 61), VH-CDR2 of SINGGGSSPTYADAVRG (SEQ ID NO: 62), VH-CDR3 of SMVGPFDY (SEQ ID NO: 63), VL-CDR1 of SGKSLSYYYAQ (SEQ ID NO: 64), VL-CDR2 of KDTERPS (SEQ ID NO: 65), VL-CDR3 of ESAVSSDTIV (SEQ ID NO: 66); or
11) a variant of 1) to 10) that differs from respective parent antibody 15H05, ZIL1, ZIL8, ZIL9, ZIL11, ZIL69, ZIL94, ZIL154, ZIL159, or ZIL171 by addition, deletion, and/or substitution of one or more amino acid residues in at least one of VH or VL CDR1, CDR2, or CDR3.

### Claim 5 (depends on 1)

The vaccine composition of claim 1, wherein the mimotope is a constrained mimotope.

### Claim 6 (depends on 5)

The vaccine composition of claim 5, wherein the constrained mimotope is a chemically-linked cyclic peptide.

### Claim 7 (depends on 1)

The vaccine composition of claim 1, wherein the mimotope is chemically conjugated to the carrier polypeptide.

### Claim 8 (depends on 1)

The vaccine composition of claim 1, wherein the carrier polypeptide and the mimotope are part of a recombinant fusion protein.

### Claim 9 (depends on 1)

The vaccine composition of claim 1, wherein the carrier polypeptide comprises a bacterial toxoid or a derivative thereof, keyhole limpet hemocyanin (KLH), or a virus-like particle.

### Claim 10 (depends on 9)

The vaccine composition of claim 9, wherein the bacterial toxoid or derivative is a tetanus toxoid, a diphtheria toxoid, a tetanus toxoid, the outer membrane protein complex from group B N. meningitidis, Pseudomonas exotoxin, or the nontoxic mutant of diphtheria toxin (CRM197).

### Claim 11 (depends on 9)

The vaccine composition of claim 9, wherein the virus-like particle is HBsAg, HBcAg, E. coli bacteriophage Qbeta, Norwalk virus, canine distemper virus (CDV), or influenza HA.

### Claim 12 (depends on 10)

The vaccine composition of claim 10, wherein the carrier polypeptide comprises or consists of CRM197.

### Claim 13 (depends on 1)

The vaccine composition of claim 1, wherein the adjuvant is selected from the group consisting of an oil-in-water adjuvant, a polymer and water adjuvant, a water-in-oil adjuvant, an aluminum hydroxide adjuvant, a vitamin E adjuvant and combinations thereof.

### Claim 14 (depends on 1)

The vaccine composition of claim 1, wherein the adjuvant is a formulation comprising a saponin, a sterol, a quaternary ammonium compound, and a polymer.

### Claim 15 (depends on 14)

The vaccine composition of claim 14, wherein the saponin is Quil A or a purified fraction thereof, the sterol is cholesterol, the quaternary ammonium compound is dimethyl dioctadecyl ammonium bromide (DDA), and the polymer is polyacrylic acid.

### Claim 16 (depends on 1)

The vaccine composition of claim 1, wherein the adjuvant comprises the combination of a sterol, a saponin, and one or more immunostimulatory oligonucleotides.

### Claim 17 (depends on 16)

The vaccine composition of claim 16, wherein the one or more isolated immunostimulatory oligonucleotides comprises CpG, the sterol is cholesterol, and the saponin is Quil A or a purified fraction thereof.

### Claim 18 (depends on 1)

A method of protecting a mammal against an IL-31 mediated disorder, the method comprising administering to the mammal a vaccine composition according to claim 1.

### Claim 19 (depends on 18)

The method of claim 18, wherein the mammal is selected from the group consisting of a dog, a cat, a horse, and a human.

### Claim 20 (depends on 18)

The method of claim 18, wherein the IL-31 mimotope contained in the vaccine composition is administered to the mammal at about 10 μg to about 100 μg per dose.