Claims for Patent: 9,717,778

Summary for Patent: 9,717,778

Title:	Combination therapy
Abstract:	The present disclosure relates to a method for treatment or prevention of diseases have an increased level of insulin-like growth factor I (IGF-I). The method comprises administration of a growth hormone (GH) variant having antagonistic activity in combination with an oligonucleotide targeted to growth hormone receptor (GHR) to a subject in need.
Inventor(s):	Tachas; George (Kew, AU)
Assignee:	Antisense Therapeutics Ltd. (Toorak, Victoria, AU)
Application Number:	14/376,390
Patent Claims:	1. A method for treatment or prevention of a disease caused by and/or associated withan increased level of insulin-like growth factor I (IGF-I) the method comprising administering to a subject in need thereof, a growth hormone (GH) variant having GH antagonistic activity and comprising the following amino acid substitutions: H18D, H21N, G120K, R167N, K168A, D171S, K172R, E174S, I179T compared with the native GH amino acid sequence shown in SEQ ID NO:2, in combination with an oligonucleotide 15 to 30 nucleobases in length comprising at least one modified internucleoside linkage, sugar moiety, or nucleobase, targeted to a nucleic acid encoding human growth hormone receptor (GHR) so as to inhibit expression of the GHR, thereby reducing the level of IGF-I in the subject, wherein the disease caused by and/or associated with an increased level of IGF-I is acromegaly, diabetic retinopathy, diabetic nephropathy, or an IGF-I positive cancer such as prostate, myeloma, lung, breast or colon cancer. 2. The method of claim 1, wherein the nucleic acid is as shown in SEQ ID NO:4 or SEQ ID NO:5. 3. The method of claim 1, wherein the oligonucleotide is a DNA oligonucleotide. 4. The method of claim 1, wherein the oligonucleotide is a RNA oligonucleotide. 5. The method of claim 4, wherein the oligonucleotide is a short interfering RNA (siRNA). 6. The method of claim 1, wherein the oligonucleotide is a chimeric oligonucleotide. 7. The method of claim 1, wherein the oligonucelotide has at least 70% complementarity with the nucleic acid encoding human GHR. 8. The method of claim 1, wherein the oligonucelotide has at least 80% complementarity with the nucleic acid encoding human GHR. 9. The method of claim 1, wherein the oligonucelotide has at least 90% complementarity with the nucleic acid encoding human GHR. 10. The method of claim 1, wherein the oligonucelotide has at least 95% complementarity with the nucleic acid encoding human GHR. 11. The method of claim 1, wherein the oligonucelotide comprises at least an 8 consecutive nucleobase portion of SEQ ID NO: 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 23, 24, 25, 26, 27, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 68, 69, 70, 71, 72, 73, 74, 75, 76, 78, 79, 80, or 81. 12. The method of claim 1, wherein the oligonucelotide consists of the nucelobase sequence of SEQ ID NOs: 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 23, 24, 25, 26, 27, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 68, 69, 70, 71, 72, 73, 74, 75, 76, 78, 79, 80, or 81. 13. The method of claim 12, wherein the oligonucleotide consists of the nucleobase sequence of SEQ ID NO:6. 14. The method of claim 1, wherein the oligonucelotide specifically hybridises with a region encoding human GHR, wherein the region comprises a translation initiation codon, a termination codon, a coding region, a 5' untranslated region, a 3' untranslated region, an intron:exon junction or an exon:intron junction. 15. The method of claim 14, wherein the region comprises at least an 8 consecutive nucleobase portion of a sequence selected from SEQ ID NOs: 84-154. 16. The method of claim 1, wherein the oligonucelotide comprises at least an 8 consecutive nucleobase portion complementary to a region of SEQ ID NO:4 selected from the group consisting of nucleotides 260- 339, 332- 351 and 344- 423 of SEQ ID NO:4. 17. The method of claim 1, wherein the oligonucelotide inhibits the expression of GHR and/or growth hormone binding protein (GHBP) by at least 15%. 18. The method of claim 1, wherein the oligonucleotide comprises at least one 2'-O-methoxyethyl sugar moiety. 19. The method of claim 1, wherein the oligonucleotide comprises at least one phosphorothioate internucleoside linkage. 20. The method of claim 1, wherein the oligonucleotide comprises at least one 5-methylcytosine. 21. The method of claim 1, wherein the oligonucleotide consists of 20 linked nucleosides, wherein the oligonucleotide consists of a nucleobase of SEQ ID NO:6; and wherein the oligonucleotide consists of a ten deoxynucleotide region flanked on both the 5' end and the 3' end of said ten deoxynucleotide region with five 2'-O-(2-methoxyethyl) nucleotides, and wherein each internucleoside linkage in the oligonucleotide is a phosphorothioate linkage, and wherein each cytosine in said oligonucleotide is a 5- methylcytosine.

Details for Patent 9,717,778

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986		2032-02-03
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2032-02-03
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2032-02-03