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 .
Status of Claims
Claims 2-4, 6, 9-11, 13, 15-17, 19 and 26-40 have been cancelled via the amendment dated 10/1/2025. Accordingly, claims 1, 5, 7-8, 12, 14, 18 and 20-25 are pending in the instant application.
Priority
This is a 35 U.S.C. 371 National Stage filing of International Application No. PCT/EP2021/068564 filed July 6th, 2021, which claims priority under 35 U.S.C. 119(a-d) to EP20184962.7, filed July 9th, 2020.
Information Disclosure Statement
The Information Disclosure Statements (IDS) filed 07/18/2025 and 10/01/2025 were considered by the Examiner.
Withdrawn Objections
Applicant’s arguments and amendments, filed October 1st, 2025, with respect to the objections of claims 5, 12 and 18 have been fully considered and are persuasive. Applicant has amended the claims to include the suggestions presented in the previous Office action, and as such, the objections of claims 5, 12 and 18 has been withdrawn.
Applicant’s arguments and amendments, filed on October 1st, 2025, with respect to the 102 rejection of claims 1-2, 7, 14-15 and 20-22 under Friese-Hamim have been fully considered and are persuasive.
Withdrawn Rejections
Applicant’s addition of the language “wherein the inhibitor is cabozantinib” in claims 1, 8 and 14 has overcome the previous art rejection. The 102 rejection of claims 1-2, 7, 14-15 and 20-22 has been withdrawn.
Response to Arguments
Applicant’s arguments and amendments, filed October 1st, 2025, with respect to the 35 USC 103 rejections, have been fully considered but they are not persuasive. Applicant’s amendments have necessitated changes to the previously presented rejections under 35 USC 103. Applicant’s arguments will be addressed as they relate to the rejections below.
On p. 7-8 of the remarks, Applicant argues that Friese-Hamim discloses Compound A (M8891), but makes no mention of cabozantinib alone or in combination. Applicant then further argues that Edwards is silent regarding M8891 and merely discloses cabozantinib individually, not in combination.
However, the argument is premised on the rationale that as both M8891 and cabozantinib are both taught in the art as being useful for the same purpose, one of ordinary skill in the art would have found the necessary motivation to combine the two compounds to form a third as to be useful for the same purpose. See MPEP 2144.06.
On p. 8 of the remarks, Applicant argues that the experimental data of the present specification shows the remarkable results of administering cabozantinib combined with compound A compared to monotherapy. Applicant points to Figures 1-3 of the instant specification to show there is a significant combination benefit.
Applicant refers to these alleged unexpected, surprising results; however, even if the results were considered unexpected, the results would not be commensurate in scope with the scope of the claims. The results provided do not occur over the entire claimed range (an amount of compound A and an amount of cabozantinib). In the instant Examples and Figures, an amount 100 mg/kg of Compound A and 10 mg/kg of cabozantinib was tested, however, the present claims do not require a specific dosage amount. Further, the Examples and Figures, are based on cell models and animal models. It is unclear how results in a cell model or animal model would correlate with treatment in a human patient.
Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). See MPEP 716.02 (d) and MPEP 716.02 (e).
An affidavit or deceleration under 37 CFR 1.132 must compare the claimed subject matter with the closes prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979).
Regardless, Applicant has not compared the unexpected results provided to the prior art to effectively rebut the prima facie case of obviousness previously set forth.
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
As the art teaches both Compound A and cabozantinib as being useful in the treatment of renal cancer, it would have been prima facie obvious to one of ordinary skill to combine them to form a third composition suitable for the same utility.
On p. 10 of the remarks, Applicant argues that Aktoudianakis does not disclose a kit with cabozantinib and M8891. Applicant further argues that the reference merely discloses a long laundry list of potential combination partners.
However, the argument is premised on the rationale that as the combination of M8891 and cabozantinib has been rendered obvious, the Aktoudianakis reference provides the necessary motivatation to include the combination in a kit.
Maintained 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 7, 14 and 20-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Friese-Hamim et al (Experimental and Molecular Therapeutics, Cancer Research, Vol.79, Issue 13, July 2019, as cited on the IDS 01/05/2023), as evidenced by Heinrich et al (J. Med. Chem. 2019, 62, 11119−11134) and Schimd et al (Ther Adv Urol. 2016 Aug 23;8(6):348–371) in view of Edwards et al (Health Technol Assess. 2018 Jan;22(6):1–278).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Friese-Hamim teaches a compound mixture of M8891 and sunitinib. M8991 is a compound of the following formula, as evidenced by Heinrich et al (J. Med. Chem. 2019, 62, 11119−11134):
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Regarding claim 7, Friese-Hamim teaches that the compound mixture is administered in a pharmaceutical setting, to renal cancer xenografts. The claim recites that the pharmaceutical composition “optionally” further comprises an excipient and/or adjuvants, thus, the claim is anticipated by the compound mixture taught by Friese-Hamim. Regarding the preamble of the instant claim “A pharmaceutical composition”, MPEP 2111.02(II) notes “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020)”. In this situation, the preamble is not considered limiting since it does not affect the structure of the compound of formula (I).
Regarding claims 14 and 21-22, Friese-Hamim teaches a method of treating patient derived renal cancer xenografts with a combination of sunitinib and M8891.
Regarding claim 20, sunitinib is a standard-of-care treatment option for renal cancer, as evidenced by Schimd et al (Ther Adv Urol. 2016 Aug 23;8(6):348–371). Schimd teaches that sunitinib has become a standard treatment option in the first-line treatment of renal cancer (abstract).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Friese-Hamim does not teach that the inhibitor is cabozantinib in the compound mixture.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
However, Edwards teaches that cabozantinib and sunitinib are a group of targeted cancer drugs that suppress cancer progression (page 30, paragraph 1). Edwards also teaches that cabozantinib is used to treat renal cell carcinoma (conclusions, page 27, paragraph 1).
Regarding claim 1, as Friese-Hamim teaches
that (S)-3-Hydroxy-1-(1H-indol-5-yl)-2-oxo-pyrrolidine-3-carboxylic acid 3,5-difluoro-benzylamide is used to treat renal cancer and Edwards teaches that cabozantinib and sunitinib are used to treat renal cancer, one of ordinary skill in the art would have been motivated to replace the inhibitor taught by Friese-Hamim, sunitinib, with cabozantinib in the compound mixture used to treat renal cancer and would have reasonable expectation of success as each compound is known in the art to be useful in the treatment of renal cancer. See MPEP 2144.06: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were k/known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine).
Claim(s) 1, 5, 7, 14, 18 and 20-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Friese-Hamim et al (Experimental and Molecular Therapeutics, Cancer Research, Vol.79, Issue 13, July 2019, as cited on the IDS 01/05/2023), as evidenced by Heinrich et al (J. Med. Chem. 2019, 62, 11119−11134) and Schimd et al (Ther Adv Urol. 2016 Aug 23;8(6):348–371) in view of National Cancer Institute (https://web.archive.org/web/20161225160745/https://www.cancer.gov/about-cancer/treatment/drugs/cabozantinib-s-malate).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Friese-Hamim teaches a compound mixture of M8891 and sunitinib. M8991 is a compound of the following formula, as evidenced by Heinrich et al (J. Med. Chem. 2019, 62, 11119−11134):
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Regarding claim 7, Friese-Hamim teaches that the compound mixture is administered in a pharmaceutical setting, to renal cancer xenografts. The claim recites that the pharmaceutical composition “optionally” further comprises an excipient and/or adjuvants, thus, the claim is anticipated by the compound mixture taught by Friese-Hamim. Regarding the preamble of the instant claim “A pharmaceutical composition”, MPEP 2111.02(II) notes “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020)”. In this situation, the preamble is not considered limiting since it does not affect the structure of the compound of formula (I).
Regarding claims 14 and 21-22, Friese-Hamim teaches a method of treating patient derived renal cancer xenografts with a combination of sunitinib and M8891.
Regarding claim 20, sunitinib is a standard-of-care treatment option for renal cancer, as evidenced by Schimd et al (Ther Adv Urol. 2016 Aug 23;8(6):348–371). Schimd teaches that sunitinib has become a standard treatment option in the first-line treatment of renal cancer (abstract).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Friese-Hamim does not teach that the inhibitor in the compound mixture alone or in the method of treating renal cancer is cabozantinib (S)-malate.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
However, National Cancer Institute teaches that cabozantinib (S)-malate is approved to treat renal cell carcinoma (page 1).
Regarding claims 5 and 18, as Friese-Hamim teaches
that (S)-3-Hydroxy-1-(1H-indol-5-yl)-2-oxo-pyrrolidine-3-carboxylic acid 3,5-difluoro-benzylamide is used to treat renal cancer and National Cancer Institute teaches that cabozantinib (S)-malate is used to treat renal cancer, one of ordinary skill in the art would have been motivated to replace the inhibitor taught by Friese-Hamim, sunitinib, with cabozantinib (S)-malate in the compound mixture used to treat renal cancer and would have reasonable expectation of success as each compound is known in the art to be useful in the treatment of renal cancer. See MPEP 2144.06: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were k/known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine).
Claim(s) 1, 7-8, 14 and 20-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Friese-Hamim et al (Experimental and Molecular Therapeutics, Cancer Research, Vol.79, Issue 13, July 2019, as cited on the IDS 01/05/2023), as evidenced by Heinrich et al (J. Med. Chem. 2019, 62, 11119−11134) and Schimd et al (Ther Adv Urol. 2016 Aug 23;8(6):348–371) in view of Aktoudianakis et al (US 2019/0270727 A1).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Friese-Hamim teaches a compound mixture of M8891 and sunitinib. M8991 is a compound of the following formula, as evidenced by Heinrich et al (J. Med. Chem. 2019, 62, 11119−11134):
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Regarding claim 7, Friese-Hamim teaches that the compound mixture is administered in a pharmaceutical setting, to renal cancer xenografts. The claim recites that the pharmaceutical composition “optionally” further comprises an excipient and/or adjuvants, thus, the claim is anticipated by the compound mixture taught by Friese-Hamim. Regarding the preamble of the instant claim “A pharmaceutical composition”, MPEP 2111.02(II) notes “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020)”. In this situation, the preamble is not considered limiting since it does not affect the structure of the compound of formula (I).
Regarding claims 14 and 21-22, Friese-Hamim teaches a method of treating patient derived renal cancer xenografts with a combination of sunitinib and M8891.
Regarding claim 20, sunitinib is a standard-of-care treatment option for renal cancer, as evidenced by Schimd et al (Ther Adv Urol. 2016 Aug 23;8(6):348–371). Schimd teaches that sunitinib has become a standard treatment option in the first-line treatment of renal cancer (abstract).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Friese-Hamim does not explicitly teach that the compound mixture formulated in a kit.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
However, Friese-Hamim teaches that a dose-escalation phase 1 study in patients with advanced solid tumors is currently ongoing.
Further, Aktoudianakis teaches kit that includes an active agent, at least one additional anticancer agent, a label and/or instructions for use of the compounds in the treatment of a disease or condition (paragraph [0074]). Aktoudianakis also teaches that the disease or condition is renal cancer. Further, Aktoudianakis teaches that the additional anticancer agent can be cabozantinib, which are both used in renal cell carcinoma combination therapy (paragraphs [0763] and [0929]). Also, Aktoudianakis teaches that (S)-3-Hydroxy-1-(1H-indol-5-yl)-2-oxo-pyrrolidine-3-carboxylic acid 3,5-difluoro-benzylamide can also be used as the additional anticancer agent (paragraph [0610]).
As such, regarding claim 8, one of ordinary skill in the art would have been motivated to alter the teachings of Friese-Hamim to formulate the compound mixture into a kit as Aktoudianakis teaches the use of a kit with cabozantinib and (S)-3-Hydroxy-1-(1H-indol-5-yl)-2-oxo-pyrrolidine-3-carboxylic acid 3,5-difluoro-benzylamide for use in treating renal cancer.
Claim 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Friese-Hamim et al (Experimental and Molecular Therapeutics, Cancer Research, Vol.79, Issue 13, July 2019, as cited on the IDS 01/05/2023), as evidenced by Heinrich et al (J. Med. Chem. 2019, 62, 11119−11134) and Schimd et al (Ther Adv Urol. 2016 Aug 23;8(6):348–371) in view of Aktoudianakis et al (US 2019/0270727 A1) and in further view of National Cancer Institute (https://web.archive.org/web/20161225160745/https://www.cancer.gov/about-cancer/treatment/drugs/cabozantinib-s-malate).
The 103 rejection of claims 1, 7-8, 14 and 20-22 over Friese-Hamim, Heinrich, Schimd and Aktoudianakis above are incorporated herein by reference.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Neither Friese-Hamim nor Aktoudianakis disclose a compound mixture or method of treating cancer that includes the inhibitor cabozantinib (S)-malate. Aktoudianakis does teach that cabozantinib is used in combination therapies to treat renal cell cancer.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
There is not a single embodiment of a kit comprising (S)-3-Hydroxy-1-(1H-indol-5-yl)-2-oxo-pyrrolidine-3-carboxylic acid 3,5-difluoro- benzylamide and cabozantinib (s)-malate.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
However, National Cancer Institute teaches that cabozantinib (S)-malate is approved to treat renal cell carcinoma (page 1).
Regarding claim 12, as Friese-Hamim teaches
that (S)-3-Hydroxy-1-(1H-indol-5-yl)-2-oxo-pyrrolidine-3-carboxylic acid 3,5-difluoro-benzylamide is used to treat renal cancer and National Cancer Institute teaches that cabozantinib (S)-malate are used to treat renal cancer, one of ordinary skill in the art would have been motivated to replace the inhibitor taught by Friese-Hamim with cabozantinib (S)-malate in the kit, rendered obvious in the above 103 rejection, used to treat renal cancer and would have reasonable expectation of success as each compound is known in the art to be useful in the treatment of renal cancer. See MPEP 2144.06: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine).
Claim(s) 1, 7, 14 and 20-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Friese-Hamim et al (Experimental and Molecular Therapeutics, Cancer Research, Vol.79, Issue 13, July 2019, as cited on the IDS 01/05/2023), as evidenced by Heinrich et al (J. Med. Chem. 2019, 62, 11119−11134) and Schimd et al (Ther Adv Urol. 2016 Aug 23;8(6):348–371) in view of Shenoy et al (Ann Oncol. 2016 Sep;27(9):1685-95).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Friese-Hamim teaches a compound mixture of M8891 and sunitinib. M8991 is a compound of the following formula, as evidenced by Heinrich et al (J. Med. Chem. 2019, 62, 11119−11134):
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Regarding claim 7, Friese-Hamim teaches that the compound mixture is administered in a pharmaceutical setting, to renal cancer xenografts. The claim recites that the pharmaceutical composition “optionally” further comprises an excipient and/or adjuvants, thus, the claim is anticipated by the compound mixture taught by Friese-Hamim. Regarding the preamble of the instant claim “A pharmaceutical composition”, MPEP 2111.02(II) notes “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020)”. In this situation, the preamble is not considered limiting since it does not affect the structure of the compound of formula (I).
Regarding claims 14 and 21-22, Friese-Hamim teaches a method of treating patient derived renal cancer xenografts with a combination of sunitinib and M8891.
Regarding claim 20, sunitinib is a standard-of-care treatment option for renal cancer, as evidenced by Schimd et al (Ther Adv Urol. 2016 Aug 23;8(6):348–371). Schimd teaches that sunitinib has become a standard treatment option in the first-line treatment of renal cancer (abstract).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Friese-Hamim does not explicitly teach that the renal cancer is clear cell renal cell carcinoma.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
However, clear cell carcinoma is a common renal cell carcinoma. Shenoy teaches that clear cell renal cell carcinoma account for 80% of all renal cell carcinoma (abstract).
Regarding claim 23, as Friese-Hamim teaches the compound mixture is used to treat renal cancer and Shenoy teaches that clear cell renal cell carcinoma accounts for 80% of all renal cell carcinoma, one of ordinary skill in the art would have been motivated by the general teachings of Friese-Hamim to administer the compound mixture to the specific population of clear cell renal cell carcinoma patients, given that is common under the umbrella of renal cell cancer, and would reasonably expect success as Friese-Hamim teaches that the mixture treats renal cancer.
Claim(s) 1, 7, 14, 20-22 and 24-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Friese-Hamim et al (Experimental and Molecular Therapeutics, Cancer Research, Vol.79, Issue 13, July 2019, as cited on the IDS 01/05/2023), as evidenced by Heinrich et al (J. Med. Chem. 2019, 62, 11119−11134) and Schimd et al (Ther Adv Urol. 2016 Aug 23;8(6):348–371).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Friese-Hamim teaches a compound mixture of M8891 and sunitinib. M8991 is a compound of the following formula, as evidenced by Heinrich et al (J. Med. Chem. 2019, 62, 11119−11134):
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Regarding claim 7, Friese-Hamim teaches that the compound mixture is administered in a pharmaceutical setting, to renal cancer xenografts. The claim recites that the pharmaceutical composition “optionally” further comprises an excipient and/or adjuvants, thus, the claim is anticipated by the compound mixture taught by Friese-Hamim. Regarding the preamble of the instant claim “A pharmaceutical composition”, MPEP 2111.02(II) notes “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020)”. In this situation, the preamble is not considered limiting since it does not affect the structure of the compound of formula (I).
Regarding claims 14and 21-22, Friese-Hamim teaches a method of treating patient derived renal cancer xenografts with a combination of sunitinib and M8891.
Regarding claim 20, sunitinib is a standard-of-care treatment option for renal cancer, as evidenced by Schimd et al (Ther Adv Urol. 2016 Aug 23;8(6):348–371). Schimd teaches that sunitinib has become a standard treatment option in the first-line treatment of renal cancer (abstract).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Friese-Hamim does not explicitly teach that (S)-3-Hydroxy-1-(1H-indol-5-yl)-2-oxo-pyrrolidine-3-carboxylic acid 3,5-difluoro- benzylamide and sunitinib are administered simultaneously or sequentially.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
However, Friese-Hamim teaches that “in combination with sunitinib, M8891” was shown to have antitumor activity in renal cancer subjects (page 1). As such, regarding claims 24-25,one of ordinary skill in the art would have been motivated by the general teachings of Friese-Hamim to screen ways to administer the two compounds, either simultaneously or sequentially, as Friese-Hamim teaches that the two compounds are administered in combination to treat renal cancer.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anna Grace Kuckla whose telephone number is (703)756-5610. The examiner can normally be reached Monday-Friday 7:30-5.
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/A.G.K./Examiner, Art Unit 1626
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699