Soluble hyaluronidase glycoprotein (sHASEGP), process for preparing the same, uses and pharmaceutical compositions comprising threreof

• US 20110152359A1
• Filed: 12/21/2010
• Published: 06/23/2011
• Est. Priority Date: 03/05/2003
• Status: Active Grant

• Current Assignee: Halozyme, Inc. (Halozyme Therapeutics, Inc.)
• Original Assignee: Halozyme, Inc. (Halozyme Therapeutics, Inc.)
• Inventors: Frost, Gregory I., Kundu, Anirban, Bookbinder, Louis H.
• Granted Patent: US 9,677,061 B2
• Time in Patent Office: Days
• US Class Current: 514/44.R
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• 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 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/24 Antidepressants
• 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 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 33/04 Amoebicides
• CPC Class Codes: A61P 33/06 : Antimalarials
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/10 : Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• 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: C12N 9/2474 : Hyaluronoglucosaminidase (3.2.1.35), i.e. hyaluronidase
• CPC Class Codes: C12Y 302/01035 : Hyaluronoglucosaminidase (3.2.1.35), i.e. hyaluronidase
• 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

Provided are soluble neutral active Hyaluronidase Glycoproteins (sHASEGP'"'"'s), methods of manufacture, and their use to facilitate administration of other molecules or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. Sialated and pegylated forms of the sHASEGPs also are provided. Methods of treatment by administering sHASEGPs and modified forms thereof also are provided.

Claims

1. A viral vector, comprising a sequence of nucleotides that encodes a C-terminal truncated PH20 polypeptide or a polypeptide having at least 91% sequence identity thereto, wherein:

the encoded truncated PH20 polypeptide comprises;

a) a sequence of amino acids contained within SEQ ID NO;

1 that includes at least amino acids 1-429 of SEQ ID NO;

4, wherein the encoded polypeptide is truncated at the C-terminus of SEQ ID NO;

1 and does not comprise the complete sequence of SEQ ID NO;

1;

or

b) a sequence of amino acids that has at least about 91% amino acid sequence identity with a sequence of a); and

with the proviso that the vector does not encode a truncated PH20 polypeptide that is the polypeptide with the sequence of amino acid residues set forth as amino acids 1-473 or 36-473 of SEQ ID NO;

1.

2. The vector of claim 1 that is an adenovirus vector.

3. The vector of claim 1 that is a retrovirus vector.

4. The vector of claim 1 that is a vaccinia virus vector.

5. The vector of claim 1, wherein the encoded truncated polypeptide has a C-terminal amino acid residue selected from among 477, 478, 479, 480, 481, 482 and 483 of SEQ ID NO:

1, or has at least 91% sequence identity thereto.

6. The vector of claim 1, comprising a sequence of nucleotides set forth in SEQ ID NO:

48.

7. The vector of claim 1, comprising a sequence of nucleotides set forth as nucleotides 106-1446 of SEQ ID NO:

6.

8. The vector of claim 1, comprising a sequence of nucleotides that encodes a signal sequence for secretion of the encoded polypeptide.

9. The vector of claim 8, wherein the signal sequence is an IgG kappa chain leader peptide.

10. The vector of claim 9, wherein the IgG kappa chain leader peptide has a sequence of nucleotides set forth in SEQ ID NO:

43.

11. An isolated cell, comprising the vector of claim 1.

12. The isolated cell of claim 11, wherein the encoded polypeptide is secreted from the cell.

13. The isolated cell of claim 11 that is a eukaryotic cell.

14. The isolated cell of claim 13 that is a mammalian cell.

15. The isolated cell of claim 13 that is a Chinese hamster ovary (CHO) cell.

16. A method, comprising administering to a patient a vector of claim 1.

17. An adenovirus vector, comprising a sequence of nucleotides that encodes a C-terminal truncated PH20 polypeptide or a polypeptide having at least 91% sequence identity thereto, wherein the encoded truncated polypeptide comprises:

a) a sequence of amino acids contained within SEQ ID NO;

1 that includes at least amino acids 1-429 of SEQ ID NO;

4, wherein the encoded polypeptide is truncated at the C-terminus of SEQ ID NO;

1 and does not comprise the complete sequence of SEQ ID NO;

1;

or

b) a sequence of amino acids that has at least about 91% amino acid sequence identity with a sequence of a).

18. The vector of claim 17, wherein the encoded truncated polypeptide has a C-terminal amino acid residue selected from among 477, 478, 479, 480, 481, 482 and 483 of SEQ ID NO:

1, or encodes a polypeptide that has at least 91% sequence identity thereto.

19. The vector of claim 17, comprising a sequence of nucleotides set forth in SEQ ID NO:

48.

20. The vector of claim 17, comprising a sequence of nucleotides set forth as nucleotides 106-1446 of SEQ ID NO:

6.

21. The vector of claim 17, comprising a sequence of nucleotides that encodes a signal sequence for secretion of the encoded polypeptide.

22. The vector of claim 21, wherein the signal sequence is an IgG kappa chain leader peptide.

23. The vector of claim 22, wherein the IgG kappa chain leader peptide has a sequence of nucleotides set forth in SEQ ID NO:

43.

24. An isolated cell, comprising the vector of claim 17.

25. The isolated cell of claim 24, wherein the encoded polypeptide is secreted from the cell.

26. The isolated cell of claim 25 that is a eukaryotic cell.

27. The isolated cell of claim 26 that is a mammalian cell.

28. The isolated cell of claim 26 that is a Chinese hamster ovary (CHO) cell.

29. A method, comprising administering to a patient a vector of claim 17.