Polypeptides

• US 10,633,438 B2
• Filed: 09/22/2016
• Issued: 04/28/2020
• Est. Priority Date: 03/31/2015
• Status: Active Grant

• Current Assignee: Sorriso Pharmaceuticals Incorporated
• Original Assignee: VHsquared Limited
• Inventors: Crowe, Scott, West, Mike, Roberts, Kevin, Carlton, Tim, Maggiore, Luana, Cubitt, Marion, Ray, Keith
• Primary Examiner(s): Sang, Hong
• Application Number:
  US15/273,353
• Publication Number:
  US 20170002069A1
• Time in Patent Office: 1,314 Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/542 oral/gastrointestinal
• 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 31/606 having amino groups
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• 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 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• 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 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/241 Tumor Necrosis Factors
• CPC Class Codes: C07K 2317/22 : from camelids, e.g. camel, llama or dromedary
• CPC Class Codes: C07K 2317/30 : characterized by aspects of specificity or valency
• CPC Class Codes: C07K 2317/33 : Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/54 : F(ab')2
• CPC Class Codes: C07K 2317/55 : Fab or Fab'
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/567 : Framework region [FR]
• CPC Class Codes: C07K 2317/569 : Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
• 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: C07K 2317/94 : Stability, e.g. half-life, pH, temperature or enzyme-resistance
• 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

There is provided inter alia a polypeptide comprising an immunoglobulin chain variable domain which binds to TNF-alpha, wherein the immunoglobulin chain variable domain comprises three complementarity determining regions (CDR1-CDR3) and four framework regions (FR1-FR4), wherein CDR1-CDR3 and FR1-FR4 are as defined in the specification.

Claims

1. A VH or VHH which binds to TNF-alpha and comprises a set of three complementarity determining regions (CDRs) comprising CDR1, CDR2 and CDR3, wherein the respective SEQ ID Nos of CDR1, CDR2 and CDR3 of said set are selected from the group consisting of:

(a) SEQ ID NO;

1, SEQ ID NO;

2 and SEQ ID NO;

3,

(b) SEQ ID NO;

1, SEQ ID NO;

63 and SEQ ID NO;

70,

(c) SEQ ID NO;

1, SEQ ID NO;

64 and SEQ ID NO;

70,

(d) SEQ ID NO;

1, SEQ ID NO;

65 and SEQ ID NO;

70,

(e) SEQ ID NO;

59, SEQ ID NO;

66 and SEQ ID NO;

71,

(f) SEQ ID NO;

60, SEQ ID NO;

67, and SEQ ID NO;

70,

(g) SEQ ID NO;

1, SEQ ID NO;

67 and SEQ ID NO;

70,

(h) SEQ ID NO;

1, SEQ ID NO;

68 and SEQ ID NO;

72,

(i) SEQ ID NO;

1, SEQ ID NO;

69 and SEQ ID NO;

70,

(j) SEQ ID NO;

1, SEQ ID NO;

62 and SEQ ID NO;

70,

(k) SEQ ID NO;

1, SEQ ID NO;

69 and SEQ ID NO;

3,

(l) SEQ ID NO;

1, SEQ ID NO;

2 and SEQ ID NO;

70,

(m) SEQ ID NO;

1, SEQ ID NO;

61 and SEQ ID NO;

70 and

(n) SEQ ID NO;

1, SEQ ID NO;

62 and SEQ ID NO;

3.

2. The VH or VHH of claim 1 which comprises SEQ ID NO:

8.

3. The VH or VHH of claim 1 wherein the CDR1 comprises the sequence of SEQ ID NO:

1, the CDR2 comprises the sequence of SEQ ID NO;

2 and the CDR3 comprises the sequence of SEQ ID NO;

3.

4. A pharmaceutical composition comprising the VH or VHH of claim 1 and one or more pharmaceutically acceptable diluents or carriers.

5. The pharmaceutical composition of claim 4, wherein the composition is presented in enterically coated form.

6. A method of treating autoimmune and/or inflammatory disease comprising administering to a person in need thereof a therapeutically effective amount of the VH or VHH of claim 1.

7. The method of treating autoimmune and/or inflammatory disease of claim 6 wherein the autoimmune and/or inflammatory disease is selected from the list consisting of Crohn'"'"'s disease, ulcerative colitis, irritable bowel syndrome, diabetes type II, glomerulonephritis, autoimmune hepatitis, Sjogren'"'"'s syndrome, celiac disease, drug- or radiation-induced mucositis, pemphigus, psoriasis, eczema and scleroderma.

8. The method of treating autoimmune disease of claim 6, wherein the VH or VHH is administered orally.