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 .
Claims 22-27, 33-35, 59-64, 69-71, 77, 78, 81 and 82 have been canceled. Claim 46 has been amended. Claims 41-46, 51-53, 79 and 80 are pending and under consideration.
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 46 and 79 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 79 requires the anti-PD-1 antibody of zimberelimab/GLS-010. Claims 46 requires the anti-PD-1 antibodies of cemiplimab, spartalizumab, tislelizumab, BI754091, dostarlimab, sasanlimab, MGA-012, cetrelimab/JNJ63723283, zimberelimab/GLS-010, camrelizumab, budigalimab/ABBV-181, or balstilimab/AGEN-2034. The specification fails to describe the required antibodies in terms of amino acid sequence of the full antibody or the variable chains of the antibody. The prior art reports on the use of said antibodies in clinical trials (Wang et al, Journal of Medicinal Chemistry, 9/24/2018, Vol. 62, pp. 1715-1730, see page 1718; Lin et al , European Journal of Medicinal Chemistry, 11/15/2019, Vol. 185, article 111873, 30 pages, see page 4), but does not describe the amino acid sequence of the full antibody or the variable chains. Thus, the prior art cannot be relied upon for a written description of the structure of the required antibodies. One of skill in the art would reasonably conclude that applicant was not in possession of the required antibodies at the time of filing.
Applicant argues that the amino acid sequence for each of the above antibodies would be readily available to a person skilled in the art from publicly accessible websites. Applicant has provided a table which provides “links” to the previously known antibody.
This has been considered but not found persuasive. Firstly, any link on the table provided by applicant has been disabled by scanning into the image file wrapper of the instant case. Secondly, it is not an issue of one of skill in the art being able to find the sequence information at the present date. The issue being applicant’s possession of the antibodies at the time of filing, which in this case is commensurate with JP2019-035603, filed 2/28/2019.
The rejection of claims 46 and 79 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement is maintained for reasons of record. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue include, but are not limited to: 1) nature of the invention, 2) state of the prior art, 3) relative skill of those in the art, 4) level of predictability in the art, 5) existence of working examples, 6) breadth of claims, 7) amount of direction or guidance by the inventor, and 8) quantity of experimentation needed to make or use the invention. In re wands, 858 F.2d 731, 737.8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
Section 2164.01 of the M.P.E.P. states
Any analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention.
Claim 79 requires the anti-PD-1 antibody of zimberelimab/GLS-010. Claims 46 requires the anti-PD-1 antibodies of cemiplimab, spartalizumab, tislelizumab, BI754091, dostarlimab, sasanlimab, MGA-012, cetrelimab/JNJ63723283, zimberelimab/GLS-010, camrelizumab, budigalimab/ABBV-181, or balstilimab/AGEN-2034. The specification fails to describe the required antibodies in terms of amino acid sequence of the full antibody or amino acid sequence of the variable chains of the antibody. The prior art reports on the use of said antibodies in clinical trials (Wang et al, Journal of Medicinal Chemistry, 9/24/2018, Vol. 62, pp. 1715-1730, see page 1718; Lin et al , European Journal of Medicinal Chemistry, 11/15/2019, Vol. 185, article 111873, 30 pages, see page 4), but does not describe the amino acid sequence of the full antibody or the variable chains. Further, said antibodies do not appear to be readily available to the public or obtainable by a repeatable method set forth in the specification. If they are not so obtainable or available, the enablement requirements of 35 USC 112, first paragraph, may be satisfied by a deposit of the appropriate cell lines / hybridomas which produce these antibodies. See 37 CFR 1.801-1.809.
In addition to the conditions under the Budapest Treaty, applicant is required to satisfy that all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon the granting of a patent in U.S. patent applications.
Amendment of the specification to recite the date of deposit and the complete name and address of the depository is required. As an additional means for completing the record, applicant may submit a copy of the contract with the depository for deposit and maintenance of each deposit.
If the original deposit is made after the effective filing date of an application for patent, the applicant should promptly submit a verified statement from a person in a position to corroborate the fact, and should state, that the biological material which is deposited is a biological material specifically identified in the application as filed, except if the person is an attorney or agent registered to practice before the Office, in which the case the statement need not be verified. See MPEP 1.804(b).
Alternatively, applicant is invited to make the record clear whether satisfaction of the requirements under 35 USC 112, first paragraph, enablement for the specific antibodies has been satisfied in a current U.S. Patent in order to make the record of the instant application complete.
Applicant argues that the amino acid sequence for each of the above antibodies would be readily available to a person skilled in the art from publicly accessible websites. Applicant has provided a table which provides “links” to the previously known antibody.
This has been considered but not found persuasive. Firstly, any link on the table provided by applicant has been disabled by scanning into the image file wrapper of the instant case. Secondly, it is not an issue of one of skill in the art being able to find the sequence information at the present date. The issue being whether the instant disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention. It is noted that applicant is claiming priority to JP2019-035603, filed 2/28/2019 and JP2019-112619, filed 6/18/2019. Providing a table with purported links to current websites does not provide the necessary information regarding disclosure of the antibody sequences in the prior art, or commercial availability of the required antibodies prior to 2/28/2019.
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 taught 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.
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.
The rejection of claims 41-46, 51-53, and 80 under 35 U.S.C. 103 as being unpatentable over Miura et al (JPWO2017150725) as evidenced by Miura et al (US2020/0281927, English Language Translation) and WIPO Bib Data in view of the abstract of Tran et al (Annals of Oncology, November 2018, vol. 29, suppl 9, abstract no. 1550) as evidenced by Chem Abstract Registry No. 1448169-71-8, downloaded from the Web 5/9/2025) is maintained for reasons of record.
After review of the BibData at WIPO, the translation thereof notes that the publication date of JPWO2017150725 is 8/9/2017. It is noted that the instant application claims priority to JP2019-112619, filed 6/18/2019 and JP2019-035603, filed 2/28/2019. Applicant has not provided an English translation of with priority doc, so it cannot be determined if said docs provide a written description of what is now claimed. Accordingly, the effective filing date is considered to be 2/28/2020. The publication of the JPWO document is outside of the grace period of 2/28/2020 and would also be outside the grace period of the ‘603 and ‘619 priority documents if they were found to be effective in the written description of the claimed invention. Thus, JPWO2017150725 constitutes prior art under 35 U.S.C. 102(a)(1), not 35 U.S.C. 102(a)(2) as stated in the prior office action.
Miura et al teach a method for treating a cancer using an FGFR inhibitor that exhibits an excellent antitumor effect and has fewer side effects (abstract). Miura et al teach that the invention provides a combination preparation for the treatment of a malignant tumor comprising a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof, and one or more additional compound(s) having an antitumor effect or pharmaceutically acceptable salt(s)(abstract). Miura et al teach that among the compounds of Formula I, (S)-1-(3-(4-amino-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)prop-2-en-1-one is preferable (paragraph [0150]), which meets the same limitation in the instant claims. Miura et al teach that additional compounds to be combined with the compounds of Formula 1 include nivolumab, atezolizumab, durvalumab, avelumab, ipilimumab, tremilimumab and abatacept (paragraphs [0156] and [0164]) which meets the limitations of claims 41-45, 51-53, 80 and 80 for an immune checkpoint inhibitor, a PD-1 pathway antagonist, an anti-PD-1 antibody, a CTLA-4 pathway antagonist, an anti-PD-L1 antibody and the limitations of claims 46 for nivolumab. Miura et al teach that the inventive method has been confirmed to be highly effective in tumors having wild-type FGFR and tumors having amplified or mutated FGFR (paragraph [0238]).
Miura et al teach the daily administration of the compounds represented by Formula I (paragraphs [0190] and [0191]) which meets the limitation of “intermittently” in claim 53. Miura et al teach that the administration of the compounds of formula 1 and the additional compound having an antitumor effect can be simultaneously, separately or sequential (paragraph [0193]) which meets the limitations of claims 52 and 53. Miura et al teach a therapeutic regimen comprising atezolizumab and the compound represented by formula 1 (paragraph [0224]) which meets the limitation of claim 43 for a CTLA-4 pathway antagonist. Miura et al teach that the methods of the invention result in long-term survival of cancer patients (paragraph [0038]) thus meeting the limitation of a sustained response after treatment cessation in claim 51.
The disclosure of Miura et al meets the limitation of “wherein said cancer patient has not been administered immune checkpoint inhibitors” in claims 41-46 and 80 absent any evidence to the contrary in the teachings of Miura et al.
Miura et al does teach that aberrant activation of FGF/FGFR signaling in human cancer is considered to be attributable to overexpression and/or gene amplification of FGFR, gene mutation chromosomal translocation or an autocrine or paracrine mechanism due to overexpression of its ligand FGFs and such aberrant signaling is considered to be partly responsible for resistance to treatment with existing chemotherapeutic antitumor agents in human cancer (paragraph [0004]). Miura et al teach that therapies targeted for FGF/FGFR signaling are expected to be able to provide medicines for enhancing the drug effects of existing chemotherapeutic antitumor agents or molecular targeting drugs, alone or in concomitant use with other medicines for cancer types that are resistant or unresponsive to these drugs (paragraph [0005]). Miura et al teach that the compound represented by Formula (I) has an excellent FGFR inhibitory effect with reduced side effects, and, when concomitantly used with various additional compounds having an antitumor effect, has an effect of enhancing the antitumor effects of the additional compounds having an antitumor effect without remarkably exacerbating toxicity.
Miura et al teach that a preferred daily dose of the compounds is 10 to 40 mg per day (paragraph [0191]). Miura et al do not teach that the therapeutically effective amount of (S)-1-(3-(4-amino-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)prop-2-en-1-one is 4 mg, 8 mg, 12 mg, 16 mg and 20 mg administered once per day which meets that limitation in claim 41.
The abstract of Tran et al teaches that TAS-120 is an irreversible inhibitor of FGFR1 through 4 demonstrating preclinical efficacy in tumor models bearing FGFR aberrations. The abstract of Tran et al teaches that in a phase I study in adult patients with advanced solid tumors, the maximum tolerated dose was found to be 20 mg. The abstract of Tran et al teaches that TAS-120 demonstrated clinical activity in patients with cholangial carcinoma, in patients with FGFR2 gene fusions and in patients who have progressed on prior treatment with other FGFR inhibitors.
CAS registry number provides evidence that TAS-120 is (S)-1-(3-(4-amino-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)prop-2-en-1-one the compound of the instant claims
REGISTRY COPYRIGHT 2025 ACS on STN
CN 2-Propen-1-one, 1-[(3S)-3-[4-amino-3-[2-(3,5-dimethoxyphenyl)ethynyl]-1H-
pyrazolo[3,4-d]pyrimidin-1-yl]-1-pyrrolidinyl]- (CA INDEX NAME)
OTHER CA INDEX NAMES:
CN 1-[(3S)-3-[4-Amino-3-[2-(3,5-dimethoxyphenyl)ethynyl]-1H-pyrazolo[3,4-
d]pyrimidin-1-yl]-1-pyrrolidinyl]-2-propen-1-one
OTHER NAMES:
CN (S)-1-[(3)-[4-Amino-3-[(3,5-dimethoxyphenyl)ethynyl]-1H-pyrazolo[3,4-
d]pyrimidine-1-yl]-1-pyrrolidinyl]-2-propen-1-one
CN 1-[(3S)-3-{4-amino-3-[(3,5-dimethoxyphenyl)ethynyl]-1H-pyrazolo[3,4-
d]pyrimidin-1-yl}pyrrolidin-1-yl]prop-2-en-1-one
CN Futibatinib
CN TAS 120
RN 1448169-71-8
It would have been prima facie obvious to carry out the methods taught by Miura et al by administering 4 mg, 8 mg, 12 mg, 16 mg and 20 mg of TAS-120 once a day. One of skill in the art would have been motivated to do so because although Miura et al teach a preferred daily dose of 10-40 mg, the abstract of Tran reporting the maximum tolerated dose of 20 mg per day and the lower doses of 4 mg, and 8mg is based on a clinical trial. One of skill in the art would be motivated to use the doses lower than 20 mg because Miura et al teach that the compound represented by Formula (I) has an excellent FGFR inhibitory effect and, when concomitantly used with various additional compounds having an antitumor effect, has an effect of enhancing the antitumor effects of the additional compounds having an antitumor effect. Because of the expected enhancement when used in combination with other anti-tumor agents, including the immune checkpoint inhibitors, there is reasonable expectation that doses lower than the maximum tolerated dose will be effective.
Applicant argues against the instant rejection claiming unexpected results. Applicant argues that administration of compound 1 alone reduced MDSCs rendering tumors more responsive to immune responses. Applicant also argues that an increase in CD4+ and CD8+ T cells resulted from compound 1 alone. Applicant further argues that the increase in CD4 and CD8 cells enhanced the effect of the immune checkpoint inhibitor. This has been considered but not found persuasive because Miura et al teaches the claimed combination of compound 1 with an immune checkpoint inhibitor. Any properties of compound 1 not taught by Miura et al would be inherent in compound 1.
Applicant further argues that the specification teaches that a high therapeutic effect can be expected from the combination of compound 1 with an immune checkpoint inhibitor. Applicant has provided the results of clinical trials supporting this on pages 5-9 of the Remarks. Applicant concludes on page 9 of the Remarks that “one of skilled in the relevant art would not have been able to predict that the co-administration of compound 1 and the immune checkpoint inhibitor would result in greatly enhanced antitumor effect. This has been considered but not found persuasive because Miura et al teaches the claimed combination of compound 1 with an immune checkpoint inhibitor. Miura et al teach that the compound represented by formula I has an excellent FGFR inhibitor effect with reduced side-effects and when concomitantly use with various additional compounds having anti-tumor effects, results I enhanced anti-tumor effect without remarkably exacerbating toxicity. Any properties of compound 1 combined with an immune checkpoint inhibitor not taught by Miura et al would be inherent in the combination.
All claims are rejected
All other rejections as set forth in the prior Office action are withdrawn.
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 KAREN A CANELLA whose telephone number is (571)272-0828. The examiner can normally be reached M-F 10-6:30.
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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/ Primary Examiner, Art Unit 1643