DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I, drawn to a method of treating at least joint disease, in the reply filed on June 16th, 2026 is acknowledged.
Applicant’s election without traverse of liraglutide, phosphate buffer, and propylene glycol in the reply filed on June 16th, 2026 is also acknowledged.
Claims 10-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on June 16th, 2026.
Claims 3, 6, and 20 are also withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on June 16th, 2026.
Priority
The instant application claims priority to 371 National Stage Application PCT/EP2022/067269, filed June 23rd, 2022, and foreign applications EP21305865.4, filed June 23rd, 2021, and EP21306467.8, filed October 21st, 2021. The priority date of June 23rd, 2021 is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) filed March 15th, 2024 is considered by the examiner.
Claims Status
The claims listing filed on June 16th, 2026 is pending. Claims 3, 6, 10-18, and 20 are withdrawn from further consideration for the reasons set forth in the restriction requirement, 37 CFR 1.142(b). Claims 1-2, 4-5, 7-9 and 19 are being examined on the merits in this office action.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 4-5, 7-9, and 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-14 of U.S. Patent No. 9592272 in view of Novo Nordisk (Novo Nordisk: "Highlights of Prescribing VICTOZA", August 2017, XP055865895,
‘272 also qualifies as prior art under 102(a)(1), so its specification is used to support the following rejection.
Regarding claim 1, ‘272 claims:
A method of treating osteoarthritis comprising administering intra-articularly a therapeutically effective dose of a peptide selected from the group consisting of a glucagon-like peptide 1 (GLP-1), a gastric inhibitory peptide (GIP) and analogues thereof resistant to dipeptidyl peptidase IV (DPP-IV) to a subject having osteoarthritis, wherein the therapeutically effective dose of the peptide or the analogue thereof inhibits or slows down the arthritic cartilage destruction. [claim 1].
‘272 further claims the method, wherein the peptide is an analogue of the GLP-1 and is resistant to DPP-IV and is selected from a group comprising of liraglutide [claims 6-8]. ‘272 does not claim the dose also comprising a buffer and a isotonic agent.
Novo Nordisk teaches that 1 mL of the VICTOZA solution contains 6 mg of liraglutide, 1.42 mg of disodium phosphate dihydrate 14 mg of propylene glycol, 5.5 mg of phenol, and water for injection [Pg 13 Section 11]. Thus, Novo Nordisk teaches an injection comprising a solution of a liraglutide, phosphate buffer, and propylene glycol.
One of ordinary skill in the art would predict that Novo Nordisk’s VICTOZA solution would be effective at treating osteoarthritis because it is simple substitution for ‘272’s known use of liraglutide as it also comprises of liraglutide and is in an injectable solution [MPEP 2143 I (B)]. Therefore, prior to the effective filing date, it was obvious to claim a method of treating at least one joint disease by administering to a patient in need thereof an effective amount of a pharmaceutical composition, wherein said pharmaceutical composition is a solution or a suspension to be administered via intraarticular injection, in particular via intraarticular injection into the joint cavity, and wherein said pharmaceutical composition comprises:
- a GLP-1R agonist,
- a buffer selected from the group consisting of a tromethamine buffer and a phosphate buffer, and
- an isotonic agent selected from the group consisting of glucose, a polyethylene glycol, propylene glycol and glycerol
because Novo Nordisk teaches such a composition and ‘272 claims the method of treating a joint disease, osteoarthritis, by administering liraglutide intraarticularly.
Regarding claim 2, ‘272 does not teach the method comprising a phosphate buffer and isotonic agent. The composition taught by Novo Nordisk comprises of the GLP-1R agonist liraglutide, the phosphate buffer disodium phosphate dihydrate, and the isotonic agent propylene glycol. Therefore, prior to the effective filing date, it was obvious to claim a method of treating at least one joint disease by administering to a patient in need thereof an effective amount of a pharmaceutical composition, wherein said pharmaceutical composition comprises a GLP-1R agonist selected from the group consisting of liraglutide, exenatide, lixisenatide, albiglutide, beinaglutide, dulaglutide, semaglutide, pegapamodutide, taspoglutide and combinations thereof, a phosphate buffer and propylene glycol because Novo Nordisk’s solution comprising liraglutide is a simple substitution for ‘272’s liraglutide and is in a solution well-suited to be injected.
Regarding claim 4, the GLP-1R agonist used by both Novo Nordisk and ‘272 is liraglutide. Therefore, prior to the effective filing date, it was obvious to claim the method of treating at least one joint disease by administering to a patient in need thereof an effective amount of a pharmaceutical composition, wherein said pharmaceutical composition comprises a GLP-1R agonist selected from the group consisting of liraglutide, exenatide, lixisenatide, albiglutide, beinaglutide, dulaglutide, semaglutide, pegapamodutide, taspoglutide and combinations thereof.
Regarding claim 19, ‘272 does not claim administering 0.0245 mg to 6.3 mg of liraglutide. However, ‘272 does specify that in one embodiment, the peptide is administered to the patient in the form of a pharmaceutical composition comprising between 1 µg and 10 mg of peptide per dose unit [Col 11 line 42]. MPEP § 2144.05(I) states: In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). Therefore, prior to the effective filing date, one of ordinary skill would find it obvious to claim the method according to claim 4, wherein the GLP-1R agonist is liraglutide and said pharmaceutical composition is to be administered at a dose ranging from 0.0245 mg to 6.3 mg of liraglutide because using a dose encompassed by the range taught by ‘272 has a reasonable expectation of success at treating osteoarthritis.
Regarding claim 7, ‘272 does not explicitly claim administering in one or at least two intraarticular injections. ‘272 specifies that in an embodiment, the peptide is an analogue of the GLP-1 peptide or of the GIP peptide, resistant to DPP-IV, and is administered by subcutaneous injection once or twice a day [Col 11 line 25]. Therefore, prior to the effective filing date, one of ordinary skill would find it obvious to claim the method according to claim 19, wherein said dose of said pharmaceutical composition is to be administered in one or at least two intraarticular injections because using the number of administrations taught by ‘272 has a reasonable expectation of success at treating osteoarthritis.
Regarding claim 5, the GLP-1R agonist used by both Novo Nordisk and ‘272 is liraglutide. Therefore, prior to the effective filing date, it was obvious to claim the method of treating at least one joint disease by administering to a patient in need thereof an effective amount of a pharmaceutical composition, wherein said pharmaceutical composition comprises of liraglutide.
Regarding claim 8, ‘272 does not claim administering doses of the pharmaceutical composition every month. However, ‘272 does specify that the GLP-1 analog can be administered at a rate of one to three injections every three months [Col 11 line 34]. The rate of three injections every three months is equivalent to the instant rate of administering monthly. Therefore, prior to the effective filing date, one of ordinary skill in the art would have found it obvious to claim the method, wherein doses of said pharmaceutical composition are to be administered every month because the method is taught by ‘272 and one could reasonably expect it to be successful.
Regarding claim 9, ‘272 does not claim that the total dose of GLP-1R agonist that is administered in one year is from 0.18 mg to 72 mg. ‘272 specifies that the GLP-1 analog can be administered at a rate of one to three injections every three months [Col 11 line 34]. ‘272 also specify that in one embodiment, the peptide is administered to the patient in the form of a pharmaceutical composition comprising between 1 µg and 10 mg of peptide per dose unit [Col 11 line 42]. This amounts to a range of 4 µg to 120 mg per year of the dose of the GLP-1 analog, depending on the frequency and dose per injection [MPEP 2144.05 (I)]. Therefore, prior to the effective filing date, one of ordinary skill would find it obvious to claim the method, wherein the total dose of GLP- 1R agonist that is administered in one year is from 0.18 mg to 72 mg because such a dose is encompassed by the range taught by ‘272 and using it has reasonable expectation of success at treating a joint disease such as osteoarthritis.
Claims 1-2 and 4-5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 15-29 of copending Application No. 17294079 in view of Novo Nordisk (Novo Nordisk: "Highlights of Prescribing VICTOZA", August 2017, XP055865895).
Regarding claim 1, ‘079 claims:
A method for cartilage regeneration in an osteoarthritis patient with lesions having a cartilage degeneration score of 3.7 or higher comprising administering to said osteoarthritis patient a composition which comprises a Glucagon Like Peptide-1 analogue, wherein the composition induces chondrocyte proliferation and/or stem cell differentiation into chondrocytes. [claim 15].
‘079 further claims the method, wherein the Glucagon Like Peptide-1 analogue is liraglutide [claims 16-17]. ‘079 does not claim the composition also comprising a buffer and an isotonic agent.
Novo Nordisk teaches that 1 mL of the VICTOZA solution contains 6 mg of liraglutide, 1.42 mg of disodium phosphate dihydrate 14 mg of propylene glycol, 5.5 mg of phenol, and water for injection [Pg 13 Section 11]. Thus, Novo Nordisk teaches an injection comprising a solution of a liraglutide, phosphate buffer, and propylene glycol.
Novo Nordisk’s solution is a simple substitution for ‘079’s liraglutide because it also comprises of liraglutide and comprises of a solution suitable for injection [MPEP 2144.05 I (B)]. Therefore, prior to the effective filing date, it was obvious to claim a method of treating at least one joint disease by administering to a patient in need thereof an effective amount of a pharmaceutical composition, wherein said pharmaceutical composition is a solution or a suspension to be administered via intraarticular injection, in particular via intraarticular injection into the joint cavity, and wherein said pharmaceutical composition comprises:
- a GLP-1R agonist,
- a buffer selected from the group consisting of a tromethamine buffer and a phosphate buffer, and
- an isotonic agent selected from the group consisting of glucose, a polyethylene glycol, propylene glycol and glycerol;
because Novo Nordisk teaches such a composition and ‘079 claims the method of treating a joint disease, osteoarthritis, by administering liraglutide intraarticularly. One of ordinary skill in the art would have a reasonable expectation of Novo Nordisk’s composition comprising liraglutide to be successful at treating the joint disease.
Regarding claim 2, ‘079 does not claim the composition also comprising a buffer and a isotonic agent. The composition taught by Novo Nordisk comprises of the GLP-1R agonist liraglutide, the phosphate buffer disodium phosphate dihydrate, and the isotonic agent propylene glycol. Therefore, prior to the effective filing date, it was obvious to claim a method of treating at least one joint disease by administering to a patient in need thereof an effective amount of a pharmaceutical composition, wherein said pharmaceutical composition comprises a GLP-1R agonist selected from the group consisting of liraglutide, exenatide, lixisenatide, albiglutide, beinaglutide, dulaglutide, semaglutide, pegapamodutide, taspoglutide and combinations thereof, a phosphate buffer and propylene glycol.
Regarding claim 4, the GLP-1R agonist used by both Novo Nordisk and ‘079 is liraglutide. Therefore, prior to the effective filing date, it was obvious to claim the method of treating at least one joint disease by administering to a patient in need thereof an effective amount of a pharmaceutical composition, wherein said pharmaceutical composition comprises a GLP-1R agonist selected from the group consisting of liraglutide, exenatide, lixisenatide, albiglutide, beinaglutide, dulaglutide, semaglutide, pegapamodutide, taspoglutide and combinations thereof.
Regarding claim 5, the GLP-1R agonist used by both Novo Nordisk and ‘079 is liraglutide. Therefore, prior to the effective filing date, it was obvious to claim the method of treating at least one joint disease by administering to a patient in need thereof an effective amount of a pharmaceutical composition, wherein said pharmaceutical composition comprises of liraglutide.
This is a provisional nonstatutory double patenting rejection.
Claims 7-9 and 19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 15-29 of copending Application No. 17294079 in view of Novo Nordisk as applied to claims 1-2 and 4-5, in further in view of Berenbaum et al. (US9592272B2; published 2017).
Regarding claim 19, ‘079 and Novo Nordisk do not claim or teach what mass of liraglutide is used to treat a joint disease like osteoarthritis. Berenbaum et al. claim a method of treating osteoarthritis comprising administering intra-articularly a therapeutically effective dose of a liraglutide [claims 1 and 6-8]. Berenbaum et al. specify that in one embodiment, the peptide is administered to the patient in the form of a pharmaceutical composition comprising between 1 µg and 10 mg of peptide per dose unit [Col 11 line 42]. MPEP § 2144.05(I) states: In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).
Therefore, prior to the effective filing date, one of ordinary skill would find it obvious to claim the method according to claim 4, wherein the GLP-1R agonist is liraglutide and said pharmaceutical composition is to be administered at a dose ranging from 0.0245 mg to 6.3 mg of liraglutide because using a dose encompassed by the range taught by Berenbaum et al. has a reasonable expectation of success at treating osteoarthritis.
Regarding claim 7, ‘079 does not explicitly claim administering in one or at least two intraarticular injections. Berenbaum et al. specify that in an embodiment, the peptide is an analogue of the GLP-1 peptide or of the GIP peptide, resistant to DPP-IV, and is administered by subcutaneous injection once or twice a day [Col 11 line 25]. Therefore, prior to the effective filing date, one of ordinary skill would find it obvious to claim the method according to claim 19, wherein said dose of said pharmaceutical composition is to be administered in one or at least two intraarticular injections because using the number of administrations taught by Berenbaum et al. has a reasonable expectation of success at treating osteoarthritis.
Regarding claim 8, ‘079 does not claim administering doses of the pharmaceutical composition every month. Berenbaum et al. specify that the GLP-1 analog can be administered at a rate of one to three injections every three months [Col 11 line 34]. The rate of three injections every three months is equivalent to the instant rate of administering monthly. Therefore, prior to the effective filing date, one of ordinary skill in the art would have found it obvious to claim the method, wherein doses of said pharmaceutical composition are to be administered every month because the method is taught by Berenbaum et al. and one could reasonably expect it to be successful.
Regarding claim 9, ‘079 does not claim that the total dose of GLP-1R agonist that is administered in one year is from 0.18 mg to 72 mg for cartilage regeneration. Berenbaum et al. teach that the GLP-1 analog can be administered at a rate of one to three injections every three months [Col 11 line 34]. Berenbaum et al. also specify that in one embodiment, the peptide is administered to the patient in the form of a pharmaceutical composition comprising between 1 µg and 10 mg of peptide per dose unit [Col 11 line 42]. This amounts to a range of 4 µg to 120 mg per year of the dose of the GLP-1 analog, depending on the frequency and dose per injection [MPEP 2144.05 (I)]. Therefore, prior to the effective filing date, one of ordinary skill would find it obvious to claim the method, wherein the total dose of GLP- 1R agonist that is administered in one year is from 0.18 mg to 72 mg because such a dose is encompassed by the range taught by Berenbaum et al. for a reasonable expectation of success at treating a joint disease such as osteoarthritis.
This is a provisional nonstatutory double patenting rejection.
Claims 1-2 and 4-5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 4-10 of copending Application No. 19016974 in view of Novo Nordisk (Novo Nordisk: "Highlights of Prescribing VICTOZA", August 2017, XP055865895).
Regarding claim 1, ‘974 claims:
A method for improving synovial membrane health in an osteoarthritis patient having abnormal synovial membrane health, comprising administering to said patient Glucagon Like Peptide-1 (GLP-1) or a GLP-1 analogue, or a composition comprising said GLP-1 or GLP-1 analogue, wherein the GLP-1 or GLP-1 analogue or the composition comprising said GLP-1 or GLP-1 analogue is administered intra-articularly, and wherein the GLP-1 or GLP-1 analogue or the composition comprising said GLP-1 or GLP- 1 analogue is administered when the patient exhibits joint swelling [claim 1].
‘974 further claims the method, wherein the GLP-1 analogue is liraglutide [claims 4-5]. ‘974 does not claim the composition also comprising a buffer and a isotonic agent.
Novo Nordisk teaches that 1 mL of the VICTOZA solution contains 6 mg of liraglutide, 1.42 mg of disodium phosphate dihydrate 14 mg of propylene glycol, 5.5 mg of phenol, and water for injection [Pg 13 Section 11]. Thus, Novo Nordisk teaches an injection comprising a solution of a liraglutide, phosphate buffer, and propylene glycol.
Novo Nordisk’s solution is a simple substitution for ‘974’s liraglutide because it also comprises of liraglutide and comprises of a solution suitable for injection [MPEP 2144.05 I (B)]. Therefore, prior to the effective filing date, it was obvious to claim a method of treating at least one joint disease by administering to a patient in need thereof an effective amount of a pharmaceutical composition, wherein said pharmaceutical composition is a solution or a suspension to be administered via intraarticular injection, in particular via intraarticular injection into the joint cavity, and wherein said pharmaceutical composition comprises:
- a GLP-1R agonist,
- a buffer selected from the group consisting of a tromethamine buffer and a phosphate buffer, and
- an isotonic agent selected from the group consisting of glucose, a polyethylene glycol, propylene glycol and glycerol
because Novo Nordisk teaches such a composition and ‘974 claims the method of treating a joint disease, osteoarthritis, by administering liraglutide intraarticularly. One of ordinary skill in the art would have a reasonable expectation of Novo Nordisk’s composition comprising liraglutide to be successful at treating the joint disease.
Regarding claim 2, ‘974 does not claim the composition also comprising a buffer and a isotonic agent. The composition taught by Novo Nordisk comprises of the GLP-1R agonist liraglutide, the phosphate buffer disodium phosphate dihydrate, and the isotonic agent propylene glycol. Therefore, prior to the effective filing date, it was obvious to claim a method of treating at least one joint disease by administering to a patient in need thereof an effective amount of a pharmaceutical composition, wherein said pharmaceutical composition comprises a GLP-1R agonist selected from the group consisting of liraglutide, exenatide, lixisenatide, albiglutide, beinaglutide, dulaglutide, semaglutide, pegapamodutide, taspoglutide and combinations thereof, a phosphate buffer and propylene glycol.
Regarding claim 4, the GLP-1R agonist used by both Novo Nordisk and ‘974 is liraglutide. Therefore, prior to the effective filing date, it was obvious to claim the method of treating at least one joint disease by administering to a patient in need thereof an effective amount of a pharmaceutical composition, wherein said pharmaceutical composition comprises a GLP-1R agonist selected from the group consisting of liraglutide, exenatide, lixisenatide, albiglutide, beinaglutide, dulaglutide, semaglutide, pegapamodutide, taspoglutide and combinations thereof.
Regarding claim 5, the GLP-1R agonist used by both Novo Nordisk and ‘974 is liraglutide. Therefore, prior to the effective filing date, it was obvious to claim the method of treating at least one joint disease by administering to a patient in need thereof an effective amount of a pharmaceutical composition, wherein said pharmaceutical composition comprises of liraglutide.
This is a provisional nonstatutory double patenting rejection.
Claims 7-9 and 19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 4-10 of copending Application No. 19016974 in view of Novo Nordisk, as applied to claims 7-9 and 19, further in view of Berenbaum et al. (US9592272B2; published 2017).
Regarding claim 19, ‘974 and Novo Nordisk do not claim or teach what mass of liraglutide is used to treat a joint disease like osteoarthritis. Berenbaum et al. claim a method of treating osteoarthritis comprising administering intra-articularly a therapeutically effective dose of a liraglutide [claims 1 and 6-8]. Berenbaum et al. specify that in one embodiment, the peptide is administered to the patient in the form of a pharmaceutical composition comprising between 1 µg and 10 mg of peptide per dose unit [Col 11 line 42]. MPEP § 2144.05(I) states: In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).
Therefore, prior to the effective filing date, one of ordinary skill would find it obvious to claim the method according to claim 4, wherein the GLP-1R agonist is liraglutide and said pharmaceutical composition is to be administered at a dose ranging from 0.0245 mg to 6.3 mg of liraglutide because using a dose encompassed by the range taught by Berenbaum et al. has a reasonable expectation of success at treating osteoarthritis.
Regarding claim 7, ‘974 does not explicitly claim administering in one or at least two intraarticular injections. Berenbaum et al. specify that in an embodiment, the peptide is an analogue of the GLP-1 peptide or of the GIP peptide, resistant to DPP-IV, and is administered by subcutaneous injection once or twice a day [Col 11 line 25]. Therefore, prior to the effective filing date, one of ordinary skill would find it obvious to claim the method according to claim 19, wherein said dose of said pharmaceutical composition is to be administered in one or at least two intraarticular injections because using the number of administrations taught by Berenbaum et al. has a reasonable expectation of success at treating osteoarthritis.
Regarding claim 8, ‘974 does not claim administering doses of the pharmaceutical composition every month. Berenbaum et al. specify that the GLP-1 analog can be administered at a rate of one to three injections every three months [Col 11 line 34]. The rate of three injections every three months is equivalent to the instant rate of administering monthly. Therefore, prior to the effective filing date, one of ordinary skill in the art would have found it obvious to claim the method, wherein doses of said pharmaceutical composition are to be administered every month because the method is taught by Berenbaum et al. and one could reasonably expect it to be successful.
Regarding claim 9, ‘974 does not claim that the total dose of GLP-1R agonist that is administered in one year is from 0.18 mg to 72 mg for cartilage regeneration. Berenbaum et al. teach that the GLP-1 analog can be administered at a rate of one to three injections every three months [Col 11 line 34]. Berenbaum et al. also specify that in one embodiment, the peptide is administered to the patient in the form of a pharmaceutical composition comprising between 1 µg and 10 mg of peptide per dose unit [Col 11 line 42]. This amounts to a range of 4 µg to 120 mg per year of the dose of the GLP-1 analog, depending on the frequency and dose per injection [MPEP 2144.05 (I)]. Therefore, prior to the effective filing date, one of ordinary skill would find it obvious to claim the method, wherein the total dose of GLP- 1R agonist that is administered in one year is from 0.18 mg to 72 mg because such a dose is encompassed by the range taught by Berenbaum et al. for a reasonable expectation of success at treating a joint disease such as osteoarthritis.
This is a provisional nonstatutory double patenting rejection.
Claims 1-2 and 4-5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-16 of copending Application No. 19391871 in view of Novo Nordisk (Novo Nordisk: "Highlights of Prescribing VICTOZA", August 2017, XP055865895).
Regarding claim 1, ‘871 claims:
A method for reducing the formation of osteophytes in an osteoarthritis patient, comprising administering to said patient Glucagon Like Peptide-1 (GLP-1) or a GLP-1 analogue, or a composition comprising said GLP-1 or GLP-1 analogue. [claim 1].
‘871 further claims the method, wherein the GLP-1 or GLP-1 analogue or the composition is administered intra-articularly, and wherein the GLP-1 analogue is liraglutide [claims 2-4]. ‘871 does not claim the composition also comprising a buffer and a isotonic agent.
Novo Nordisk teaches that 1 mL of the VICTOZA solution contains 6 mg of liraglutide, 1.42 mg of disodium phosphate dihydrate 14 mg of propylene glycol, 5.5 mg of phenol, and water for injection [Pg 13 Section 11]. Thus, Novo Nordisk teaches an injection comprising a solution of a liraglutide, phosphate buffer, and propylene glycol.
Novo Nordisk’s solution is a simple substitution for ‘871’s liraglutide because it also comprises of liraglutide and comprises of a solution suitable for injection [MPEP 2144.05 I (B)]. Therefore, prior to the effective filing date, it was obvious to claim a method of treating at least one joint disease by administering to a patient in need thereof an effective amount of a pharmaceutical composition, wherein said pharmaceutical composition is a solution or a suspension to be administered via intraarticular injection, in particular via intraarticular injection into the joint cavity, and wherein said pharmaceutical composition comprises:
- a GLP-1R agonist,
- a buffer selected from the group consisting of a tromethamine buffer and a phosphate buffer, and
- an isotonic agent selected from the group consisting of glucose, a polyethylene glycol, propylene glycol and glycerol
because Novo Nordisk teaches such a composition and ‘871 claims the method of treating a joint disease, osteoarthritis, by administering liraglutide intraarticularly. One of ordinary skill in the art would have a reasonable expectation of Novo Nordisk’s composition comprising liraglutide to be successful at treating the joint disease.
Regarding claim 2, ‘871 does not claim the composition also comprising a buffer and a isotonic agent. The composition taught by Novo Nordisk comprises of the GLP-1R agonist liraglutide, the phosphate buffer disodium phosphate dihydrate, and the isotonic agent propylene glycol. Therefore, prior to the effective filing date, it was obvious to claim a method of treating at least one joint disease by administering to a patient in need thereof an effective amount of a pharmaceutical composition, wherein said pharmaceutical composition comprises a GLP-1R agonist selected from the group consisting of liraglutide, exenatide, lixisenatide, albiglutide, beinaglutide, dulaglutide, semaglutide, pegapamodutide, taspoglutide and combinations thereof, a phosphate buffer and propylene glycol.
Regarding claim 4, the GLP-1R agonist used by both Novo Nordisk and ‘871 is liraglutide. Therefore, prior to the effective filing date, it was obvious to claim the method of treating at least one joint disease by administering to a patient in need thereof an effective amount of a pharmaceutical composition, wherein said pharmaceutical composition comprises a GLP-1R agonist selected from the group consisting of liraglutide, exenatide, lixisenatide, albiglutide, beinaglutide, dulaglutide, semaglutide, pegapamodutide, taspoglutide and combinations thereof.
Regarding claim 5, the GLP-1R agonist used by both Novo Nordisk and ‘871 is liraglutide. Therefore, prior to the effective filing date, it was obvious to claim the method of treating at least one joint disease by administering to a patient in need thereof an effective amount of a pharmaceutical composition, wherein said pharmaceutical composition comprises of liraglutide.
This is a provisional nonstatutory double patenting rejection.
Claims 7-9 and 19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-16 of copending Application No. 19391871 in view of Novo Nordisk, as applied to claims 1-2 and 4-5, further in view of Berenbaum et al. (US9592272B2; published 2017).
Regarding claim 19, ‘871 and Novo Nordisk do not claim or teach what mass of liraglutide is used to treat a joint disease like osteoarthritis. Berenbaum et al. claim a method of treating osteoarthritis comprising administering intra-articularly a therapeutically effective dose of a liraglutide [claims 1 and 6-8]. Berenbaum et al. specify that in one embodiment, the peptide is administered to the patient in the form of a pharmaceutical composition comprising between 1 µg and 10 mg of peptide per dose unit [Col 11 line 42].
Therefore, prior to the effective filing date, one of ordinary skill would find it obvious to claim the method according to claim 4, wherein the GLP-1R agonist is liraglutide and said pharmaceutical composition is to be administered at a dose ranging from 0.0245 mg to 6.3 mg of liraglutide because using a dose encompassed by the range taught by Berenbaum et al. has a reasonable expectation of success at treating osteoarthritis [MPEP 2144.05(I)].
Regarding claim 7, ‘871 does not explicitly claim administering in one or at least two intraarticular injections. Berenbaum et al. specify that in an embodiment, the peptide is an analogue of the GLP-1 peptide or of the GIP peptide, resistant to DPP-IV, and is administered by subcutaneous injection once or twice a day [Col 11 line 25]. Therefore, prior to the effective filing date, one of ordinary skill would find it obvious to claim the method according to claim 19, wherein said dose of said pharmaceutical composition is to be administered in one or at least two intraarticular injections because using the number of administrations taught by Berenbaum et al. has a reasonable expectation of success at treating osteoarthritis.
Regarding claim 8, ‘871 does not claim administering doses of the pharmaceutical composition every month. Berenbaum et al. specify that the GLP-1 analog can be administered at a rate of one to three injections every three months [Col 11 line 34]. The rate of three injections every three months is equivalent to the instant rate of administering monthly. Therefore, prior to the effective filing date, one of ordinary skill in the art would have found it obvious to claim the method, wherein doses of said pharmaceutical composition are to be administered every month because the method is taught by Berenbaum et al. and one could reasonably expect it to be successful.
Regarding claim 9, ‘871 does not claim that the total dose of GLP-1R agonist that is administered in one year is from 0.18 mg to 72 mg for cartilage regeneration. Berenbaum et al. teach that the GLP-1 analog can be administered at a rate of one to three injections every three months [Col 11 line 34]. Berenbaum et al. also specify that in one embodiment, the peptide is administered to the patient in the form of a pharmaceutical composition comprising between 1 µg and 10 mg of peptide per dose unit [Col 11 line 42]. This amounts to a range of 4 µg to 120 mg per year of the dose of the GLP-1 analog, depending on the frequency and dose per injection [MPEP 2144.05 (I)]. Therefore, prior to the effective filing date, one of ordinary skill would find it obvious to claim the method, wherein the total dose of GLP- 1R agonist that is administered in one year is from 0.18 mg to 72 mg because such a dose is encompassed by the range taught by Berenbaum et al. for a reasonable expectation of success at treating a joint disease such as osteoarthritis.
This is a provisional nonstatutory double patenting rejection.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2, 4-5, 7-9, and 19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating osteoarthritis, does not reasonably provide enablement for treating all joint diseases. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The breadth of claim encompasses using a GLP-1R agonist to treat any condition that falls under the genus of joint diseases. The specification defines “treating” as “any action which makes it possible to prevent, delay, reduce in severity and/or frequency or suppress at least one symptom associated with a pathological condition, or to prevent, slow down or suppress the underlying cause of a pathological condition, or the improvement or remediation of damage” [0124]. The invention’s nature is therapeutic, comprising a GLP-1 agonist. The genus “GLP-1 agonist” is not limited to long-acting peptide agonists but also includes peptides that are not modified for extended use and small molecules. However, the state of the prior art does not support that all GLP-1 agonists can treat all types of joint diseases. (Krishnan, Y., & Grodzinsky, A. J. (2018). Cartilage diseases. Matrix biology: journal of the International Society for Matrix Biology, 71-72, 51–69)
Krishnan et al. state that cartilage diseases can range from common conditions such as osteoarthritis, which is estimated to affect as many as 37% of all adults in the United States, to rare genetic disorders such as Spondyloepimetaphyseal dysplasia (SEMD) [pg 53 pgh 4 line 1]. Also, in addition to external injuries that can affect the hyaline cartilage, which plays a crucial role in skeletal growth and development, genetic mutations can also affect growth plate cartilage, causing conditions like chondrodysplasia [pg 53 pgh 5 and 6]. There are also cartilaginous tumors, including osteochondroma, enchondroma, periosteal chondroma, multiple chondromatosis and enchondromatosis [pg 56 pgh 7 line 2]. Thus, Krishnan et al. teach that the genus of cartilage diseases encompasses diverse etiologies. One of ordinary skill in the art would recognize that genetic and cancerous cartilage diseases cannot be treated by targeting the glucagon receptor. Furthermore, such a method of treatment lacks the predictability of being successful.
The inventors provide working examples by preparing formulations comprising of 6 mg/mL of liraglutide with various isotonic agents [0283] and testing the formulations and Victoza’s (liraglutide) in vitro efficacy on a RAW 264.7 cell culture, in a nitrite oxide dosage assay, and on murine primary chondrocytes [0313-0358]. The inventors then tested the efficacy of intra-articular knee injection on monosodium iodoacetate-induced model of osteoarthritis and inflammatory pain in rats, with the formulations comprising 6 mg/mL of liraglutide and various isotonic agents, Victoza (liraglutide), Ozempic (semaglutide), Bydureon (exenatide), and Adlyxin (lizisenatide) [0399-0465]. The inventors concluded that the GLP-1R agonists have dose-dependent analgesic effects. Lastly, the inventors conducted a phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics, and efficacy of intra-articularly administered liraglutide in patients with knee osteoarthritis [0730]. The inventors provide adequate support in the specification for the treatment of osteoarthritis. However, the treatment of osteoarthritis does not extend the predictability that a GLP-1R agonist would be able to treat all types of joint diseases. Although the prior art recognizes the monosodium iodoacetate-induced model of osteoarthritis and inflammatory pain in rats, the prior art does not recognize it as a model for all other joint conditions. Furthermore, the Examiner is not aware of prior art teaching that the GLP-1R is a valid therapeutic target for all other joint conditions. Only GLP-1R peptide agonists were tested by the inventor.
Moreover, in order to practice the full scope of the claimed invention, Applicant would be burdened with discovering which additional joint disorders can be treated with GLP-1 agonists. The requirement to discover, test, and validate constitutes undue experimentation. Thus, while the applicant is enabled for the scope of treating osteoarthritis, the inventor is not enabled for treating the complete genus of joint diseases.
Claims 2, 4-5, 7-9, and 19 do not further limit the treated joint diseases in base claim 1, and are therefore rejected for not being used by in a manner enabled by the specifications and prior art.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 7 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form. Claim 7 references claim 19, which has not been previously set forth. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2, 4-5, 7-9, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over in view of Berenbaum et al. (US9592272B2; published 2017) in view of Novo Nordisk (Novo Nordisk: "Highlights of Prescribing VICTOZA", August 2017, XP055865895, www.accessdata.fda.gov/drugsatfda_docs/label/2017/022341s027lbl.pdf)
Berenbaum et al. claim:
A method of treating osteoarthritis comprising administering intra-articularly a therapeutically effective dose of a peptide selected from the group consisting of a glucagon-like peptide 1 (GLP-1), a gastric inhibitory peptide (GIP) and analogues thereof resistant to dipeptidyl peptidase IV (DPP-IV) to a subject having osteoarthritis, wherein the therapeutically effective dose of the peptide or the analogue thereof inhibits or slows down the arthritic cartilage destruction. [claim 1].
Berenbaum further claim the method wherein the peptide is an analogue of the GLP-1 and is resistant to DPP-IV and is selected from a group comprising of liraglutide [claims 6-8]. Berenbaum et al. do not teach the therapeutically effective dose further comprising a phosphate buffer and propylene glycol.
Novo Nordisk teaches that 1 mL of the VICTOZA solution contains 6 mg of liraglutide, 1.42 mg of disodium phosphate dihydrate 14 mg of propylene glycol, 5.5 mg of phenol, and water for injection [Pg 13 Section 11]. Thus, Novo Nordisk teaches an injection comprising a solution of a liraglutide, phosphate buffer, and propylene glycol. Novo Nordisk does not teach administering the VICTOZA solution via intraarticular injection to treat at least one joint disease.
Therefore, prior to the effective filing date, it was obvious to administer a composition comprising liraglutide, a phosphate buffer, and propylene glycol because Novo Nordisk teaches such a composition and Berenbaum teaches the method of treating a joint disease, osteoarthritis, by administering liraglutide intraarticularly. One of ordinary skill in the art would have a reasonable expectation of Novo Nordisk’s composition comprising liraglutide to be successful at treating the joint disease because Novo Nordisk’s solution is a simple substitution and is suitable for injection [MPEP 2144.05 I (B)].
Regarding claim 2, the composition taught by Novo Nordisk comprises of the GLP-1R agonist liraglutide, the phosphate buffer disodium phosphate dihydrate, and the isotonic agent propylene glycol.
Regarding claims 4 and 5, the GLP-1R agonist used by both Novo Nordisk and Berenbaum is liraglutide.
Regarding claim 19, Berenbaum et al. specify that in one embodiment, the peptide is administered to the patient in the form of a pharmaceutical composition comprising between 1 µg and 10 mg of peptide per dose unit [Col 11 line 42].
MPEP § 2144.05(I) states: In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).
In the instant case, the claimed range 0.245 mg to 6.3 mg lies inside the prior art range 1 µg and 10 mg. Therefore, the claimed range is prima facie obvious over the prior art.
Regarding claim 7, Berenbaum et al. also specify that in an embodiment, the peptide is an analogue of the GLP-1 peptide or of the GIP peptide, resistant to DPP-IV, and is administered by subcutaneous injection once or twice a day [Col 11 line 25]. Therefore, prior to the effective filing date, one of ordinary skill would find it obvious to use the frequency of administrations taught by Berenbaum for a reasonable expectation of success at treating osteoarthritis.
Regarding claim 8, Berenbaum et al specify that the GLP-1 analog can be administered at a rate of one to three injections every three months [Col 11 line 34]. The rate of three injections every three months is equivalent to the instant rate of administering monthly. Therefore, prior to the effective filing date, one of ordinary skill in the art would have found it obvious to administer the pharmaceutical composition every month because the method is taught by Berenbaum and one could reasonably expect it to be successful.
Regarding claim 9, Berenbaum specify that the GLP-1 analog can be administered at a rate of one to three injections every three months [Col 11 line 34]. Berenbaum et al. also specify that in one embodiment, the peptide is administered to the patient in the form of a pharmaceutical composition comprising between 1 µg and 10 mg of peptide per dose unit [Col 11 line 42]. This amounts to a range of 4 µg to 120 mg per year of the dose of the GLP-1 analog, depending on the frequency and dose per injection [MPEP 2144.05(I)]. Therefore, prior to the effective filing date, one of ordinary skill would find it obvious to use a dose encompassed by the range taught by Berenbaum for a reasonable expectation of success at treating a joint disease such as osteoarthritis.
Conclusion
Claims 1-2, 4-5, 7-9 and 19 are rejected on the ground of nonstatutory double patenting. Claims 1-2, 4-5, 7-9 and 19 are also provisionally rejected on the ground of nonstatutory double patenting. Claims 1-2, 4-5, 7-9, and 19 are rejected under 35 U.S.C. 112(a). Claim 7 is rejected under 35 U.S.C. 112(d). Claims 1-2, 4-5, 7-9, and 19 are rejected under 35 U.S.C. 103.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SACHI JAUHARI whose telephone number is (571)272-3769. The examiner can normally be reached Mon-Fri 9-4.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SACHI JAUHARI/ Examiner, Art Unit 1654
/CHRISTINA M MARCHETTI BRADLEY/ Primary Examiner, Art Unit 1654
Prosecution Insights