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 .
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.
Election/Restrictions
Examiner is maintaining 103 rejections and double patenting rejection on file.
Applicant narrowed the HIF-2 inhibitor to belzutifan and disease renal cell carcinoma (RCC). Thus, election of species requirement is withdrawn.
Claims 1, 4-9 and 20-27 are examined on merits.
Current Status of 18/009,115
This office action is in response to the amended claims on 02/27/2026.
Claims 1, 4, 7-9 and 20 are currently amended; 5-7, 10, 21-22 and 24-26 are original; and claims 23 and 27 are previously present.
Claims 1, 4-9 and 20-27 are examined in this office action.
Priority
The effective filing date is 06/22/2020 since the instant claims find support in provisional application no. 63/042,307.
Response to Amendment
Examiner acknowledges the receipt of applicant’s claim amendment and remarks of 02/27/2026. Examiner have reviewed these remarks and amendments.
Applicant narrowed the HIF-2 inhibitor to belzutifan and disease renal cell carcinoma (RCC). Thus, election of species requirement is withdrawn.
Regarding 103 rejection.
Applicant argues:
Applicant argues in page 6 of the remark, targeted therapy combinations for advanced clear cell renal cell carcinoma showed higher response rates with belzutifan + Lenvatinib compared to pembrolizumab +belzutifan or pembrolizumab+ Lenvatinib.
Applicant claims surprising and unexpected results (page 7 of remarks) with belzutifan+lenvatinib combination showing the highest response rates compared with other monotherapy and combination therapies tested, with an ORR of 50.0% compared with 22.6% for pembrolizumab+belzutifan, and 43.8% for pembrolizumab+lenvatinib.
Examiner Response.
Applicant provided evidence in exhibit A, B and C (see page 6-7 in the remarks) of surprising and unexpected result, however these result are not reflected in the specification. Therefore, there is no evidence in the specification for surprising and unexpected results. Therefore 103 rejection is maintained.
Applicant is encouraged to file declaration of affidavit to overcome 103 rejection, with evidence of surprising and unexpected results.
Regarding double patenting rejections. Applicant did not amend the claims to over the anticipatory and obvious-type double patenting rejections. Therefore, double patenting rejections are maintained.
Claim Rejections - 35 USC § 103 (Maintained)
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.
Claims 1, 4-9 and 20-27 are rejected under 35 U.S.C. 103 as being unpatentable over
Xu et. al. J. Med. Chem. 2019, 62, 6876−6893.
In view of
Jonasch et. al (Journal of clinical oncology Meeting Abstract Genitourinary Cancers Symposium, Renal Cell Cancer, abstract, 611 published February 19 2020)
In view of
Grunwald et.al. (Future Oncol. (2019) 15(9), 929–941)
In further view of
Inman (OnLive , May 13, 2016 pages 1-6)
1. Determining the scope and contents of the prior art.
Xu et.al discloses method of treating clear cell renal cell carcinoma (ccRCC, applicant’s elected species, with HIF-2α inhibitor, belzutifan(
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, applicant’s elected species) (abstract) in clinical trial in patient partially teaching claims 1. 4, and 9. Belzutifan is administered 40mg, 80mg or 120 mg once daily (page 6885, table 6) teaching claims 20-22 and partially teaching claims 24-25. In ccRCC, VHL is defective or absent (page 6876), thus teaching claims 8.
Jonasch et. al teaches patients with advanced ccRCC (claims 4) who had received at least 1 prior therapy (where prior treatment received was anti-PD-1 and anti VEGF agents, (claim 6)) with 120mg of MK-6482(belzutifan) administered daily (claims 20-22 and 24-25) (abstract), partially teaching claims 1, 4-6, 9, 20-22 and 24-25.
Grunwald et.al. teaches the method of treating advance RCC where advance RCC is ccRCC comprising administrating Lenvatinib in patient (page 929, abstract) partially teaching claims 1,4, 7 and 9. Grunwald further teaches treatment of metastatic RCC once daily with 18mg and 20mg (claim 24) of Lenvatinib (page 931) teaching claims 23-24.
Inman teaches the use of Lenvatinib mesylate (claim 27) (lenvima, FDA approved) to treat advance RCC partially teaching claims 1, 4.
2. Ascertaining the differences between the prior art and the claims at issue.
Xu et.al does not teach the combination belzutifan and Lenvatinib for treating ccRCC.
Jonasch et.al does not teach the combination belzutifan and Lenvatinib for treating ccRCC.
Grunwald et.al does not teach the combination belzutifan and Lenvatinib for treating ccRCC.
Inman et.al does not teach the combination belzutifan and Lenvatinib for treating ccRCC.
3. Resolving the level of ordinary skill in the pertinent art.
The level of ordinary skill is an artisan who have sufficient background in developing treatment for ccRCC and is looking improve the outcome of the treatment.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Belzutifan, HIF-α2 inhibitor is known in the art for treating ccRCC (Xu et.al, abstract and Jonasch , abstract) and Lenvatinib also known in the art for treating ccRCC(Grunwald, page 929, abstract). Therefore, a person skilled in the art would be motivated to combine belzutifan with Lenvatinib to treat ccRCC since the combination of belzutifan and Lenvatinib is expected to be more effective or have similar effect in treating ccRCC than a composition comprising just one of belzutifan or lenvatinib. Moreover, it is expected that a person skilled in the art would use the combination of Lenvatinib and belzutifan to treat metastatic RCC (claims 7) since the belzutifan and Lenvatinib can each individually treat RCC. Furthermore, a person skilled in the art would be expected to use lenvima mesylate salt of lenvatinib) (Inman, page 1), since lenvima is already FDA approved, in combination with belzutifan. Thus combination of Belzutifan with Lenvatinib is expected to treat ccRCC in patients thus teaching claims 1, 4-8 and 24
Claim 9 are directed to a kit containing instruction for administering to HIF-α2 inhibitor and Lenvatinib which is obvious given Lenvatinb and belzutifan are already used in clinical trial (see above) and the phrase “kit” or “instruction” does not add any patentable elements to the claims. “Nonfunctional printed matter does not distinguish claimed product from otherwise identical prior art product.” See MPEP 2112.01(III).
Claims 20-26 are directed to dosage of belzutifan and lenvatinib administered to patients. Examiner interprets these attributes as variables the artisan would normally be expected to routinely optimize. For example, dosages of pharmaceuticals are routinely optimized based on body weight and body surface area (Anisel et.al. “PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY SYSTEMS” page 50). Generally, dosage will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such attributes are critical. Therefore, second treatment of compound I is considered to be routine optimization (thus teaching claims 20-26) “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). See MPEP 2144.05(II)(A).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
Double Patenting (maintained)
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, 4-5, 7, 9 and 20-24 provisionally rejected on the ground of anticipatory nonstatutory double patenting as being anticipated over claim 1,5-7,9,35 and 37-39 of co-pending Application No. 18/009,109 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because reference claims 1,5-6, teaches combination of HIF-2α inhibitor belzutifan and Lenvatinib in treating advance ccRCC same as instant claims 1 and 4-5. Reference claim 7 recites RCC is metastatic RCC, same as instant claim 7. Reference claim 9 teaches a kit with combinations of belzutifan and lenvatinib, same as instant claims 9. Reference claim 35 teaches method of administering belzutifan in the amount of 40mg-120mg once daily same as instant claim 20-21. Reference claim 37 teaches method of administering belzutifan in the amount of 120mg same as instant claim 22. Reference claim 38 teaches method of administering lenvatinib in the amount of 8, 10,14,18, 20 or 24 mg same as instant claim 23. Reference claim 39 teaches method of treating RCC by administering 120mg of belzutifan and 20mg of lenvatinib same as instant claim 24.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 4-9 and 20-27 provisionally rejected on the ground of obviousness-type nonstatutory double patenting as being obvious over claims 1,5-7,9,35 and 37-39 of copending Application No. 18/009,109
In view of
Xu et. al. J. Med. Chem. 2019, 62, 6876−6893.
In view of
Jonasch et. al (Journal of clinical oncology Meeting Abstract Genitourinary Cancers Symposium, Renal Cell Cancer, abstract, 611 published February 19 2020)
In further view of
Inman (OnLive, May 13, 2016 pages 1-6)
1. Determining the scope and contents of the prior art.
Reference claims 1,5-7,9,35 and 37-39 of copending Application No. 18/009,109 is same as instant claims 1, 4-5, 7,9 and 20-24 (see above).
Xu et.al teaches VHL is defective or absent (page 6876) in ccRCC, thus teaching claims 8.
Jonasch et. al teaches patients with advanced ccRCC (claims 4-5) who had received at least 1 prior therapy, where prior treatment received was anti-PD-1 and anti VEGF agents, (claim 6) with 120mg of MK-6482(belzutifan) administered daily (claims 20-22 and 24-25) (abstract), partially teaching claims 1, 4-6, 9, 20-22 and 24-25.
Inman teaches the use of lenvatinib mesylate (claim 27) (lenvima, FDA approved) to treat advance RCC partially teaching claims 1-4.
2. Ascertaining the differences between the prior art and the claims at issue.
Xu et.al does not teach the combination belzutifan and Lenvatinib for treating ccRCC.
Jonasch et.al does not teach the combination belzutifan and Lenvatinib for treating ccRCC.
Inman et.al does not teach the combination belzutifan and Lenvatinib for treating ccRCC.
3. Resolving the level of ordinary skill in the pertinent art.
The level of ordinary skill is an artisan who have sufficient background in developing treatment for ccRCC and is looking to improve the outcome of the treatment.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Reference claims 1,5-7,9,35 and 37-39 teaches instant claims 1, 4-5, 7,9 and 20-24. Xu et.al teaches VHL is absent or defective in ccRCC (Xu et.al 6876), therefore it would be obvious to propose instant claim 8 combined with reference claims 1 and 5-6 of copending application US No. 18/009,109. Furthermore, a person skilled in the art would be expected to use Lenvima (mesylate salt of Lenvatinib, since Lenvima is already FDA approved) (Inman, page 1), in combination with reference claims 1 and 5-6 of copending application US No. 18/009,109, same as instant claim 27.
Jonasch teaches method of treating advance ccRCC who had received at least 1 prior therapy where prior treatment received was anti-PD-1 and anti VEGF agents (Jonasch et. al. abstract) therefore it would be obvious to use combination of belzutifan and Lenvatinib from reference claims 1 and 5-6 in patients who had received prior treatment with anti-PD-1 and anti-VEGF-agent same as instant claim 6.
Claims 9 are directed to a kit containing instruction for administering to HIF-α2 inhibitor and Lenvatinib which is obvious given Lenvatinib and belzutifan are already used in clinical trial (see above) and the phrase “kit” or “instruction” does not add any patentable elements to the claims. “Nonfunctional printed matter does not distinguish claimed product from otherwise identical prior art product.” See MPEP 2112.01(III).
Claims 20-26 are directed to dosage of belzutifan and Lenvatinib administered to patients. Examiner interprets these attributes as variables the artisan would normally be expected to routinely optimize. For example, dosages of pharmaceuticals are routinely optimized based on body weight and body surface area (Anisel et.al. “PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY SYSTEMS” page 50). Generally, dosage will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such attributes are critical. Therefore, second treatment of compound I is considered to be routine optimization (thus teaching claims 20-26) “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). See MPEP 2144.05(II)(A).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
Conclusion
No claims are allowed as written.
Applicant is encouraged to file declaration or affidavit detailing unexpected / surprising results of the full scope of each rejected independent claim to overcome 103 rejection.
Applicant is encouraged to file terminal disclaimer to overcome double patenting rejections.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 Rehana Ismail whose telephone number is (703)756-4776. The examiner can normally be reached Monday-Friday 9:00am-5:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew D Kosar can be reached at (571)272-913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/R.I./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
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