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 .
Priority
This application is a CON of PCT/CN2025/074930 (01/24/2025)
and claims foreign priority to CHINA 202410153995.9 (02/02/2024)
CHINA 202410200806.9 (02/22/2024)
CHINA 202410245467.6 (03/04/2024)
CHINA 202410346358.3 (03/25/2024).
Status
Claims 1, 10, 11, 14-18 and 21-23 are pending with claims 14-17 and 21-23 held withdrawn.
Election/Restrictions
Applicant affirmed election without traverse of Group I, claims 1-13, 18 and the following species in the reply of 7/21/2026.
Applicant also elected the following species of the 4th compound of claim 8:
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corresponding to claim 1’s Formula (I) where R1 is H, R2 is CH3, and R3 is CF3 and determined to read on claims 1-5, 8-13, and 18.
As detailed in the following rejections, the generic claim encompassing the elected species was not found patentable. Therefore, the provisional election of species is given effect, the examination is restricted to the elected species only, and claims not reading on the elected species are held withdrawn. MPEP 803.02; Ex parte Ohsaka, 2 USPQ2d 1460, 1461 (Bd. Pat. App. lnt. 1987). Accordingly, claims 6-7 are hereby withdrawn.
Should applicant, in response to this rejection of the Markush-type claim, overcome the rejection through amendment, the amended Markush-type claim will be reexamined to the extent necessary to determine patentability of the Markush-type claim. See MPEP 803.02.
Claim Rejections - 35 USC § 103
Claims 1, 10-11, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Deng et al. (US20250382296, filed 2023-06-26) in view of Hu et al. (Front. Immunol. 12:722188, 2022-01-17, 13 pages).
Deng teaches PRTM5 inhibitors for treating cancer in a subject, including the following compound (claim 20, p. 149; claims 22-25):
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Deng’s compound is the same as the elected species.
Deng does not teach a combination with the PD-L1 inhibitor nivolumab.
Hu teaches PRMT5 inhibition in combination with anti-PD-L1 therapy was successful and was a promising strategy for lung cancer therapy (p. 10: “combined PRMT5 inhibition and anti-PD-L1 antibody therapy influences CD8 T cell function and achieved better effects compared with single-agent therapy”; p. 12: “Overall, our findings address an unmet clinical need through the combination of PRMT5 inhibition and anti-PD-L1 therapy, which may represent a promising strategy for lung cancer therapy”). Hu specifically teaches “anti-PD1 mAb (nivolumab)” and atezolizumab for lung cancer treatment and that targeting oncogenesis factors represents a promising strategy to treat lung cancer (p. 2).
The level of skill in the art is very high such that one of ordinary skill in the art would consider routine the combinations of anticancer compounds to improve therapeutic effect. One of ordinary skill in the art would consider routine and well within their technical grasp the process of combining anti-cancer therapies as suggested by the prior art, specifically PRMT5 inhibitor with anti-PD-L1 therapies. In addition, those of ordinary skill in the art would first look to successful therapies already known in the art.
“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, 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, 126 USPQ 186 (CCPA 1960) (the “joint use [of magnesium oxide and calcium carbide] is not patentable” where the prior art teaches “that both magnesium oxide and calcium carbide, individually, promote the formation of a nodular structure in cast iron, and it would be natural to suppose that, in combination, they would produce the same effect and would supplement each other”); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious).
See also Merck & Co., Inc. v. Biocraft Labs, Inc., 874 F.2d 804, 808 (Fed. Cir. 1989) (“Given the prior art teaching that both amiloride and hydrochlorothiazide are natriuretic, it is to be expected that their coadministration would induce more sodium excretion than would either diuretic alone”); In re Diamond, 360 F.2d 214, 217 (CCPA 1966) (where the evidence showed that synergy was expected because combined drugs targeted different cellular mechanisms, and no evidence to the contrary was produced, “[w]e are not convinced of [the] non-obviousness of the combination of two drugs, A5MP and a glucocorticoid . . . particularly since Appeal the record supports the [PTO’s] contention that the drugs selected are two of the commonly used drugs in the treatment of such collagen diseases”).
In this case, the Deng teaches the PRMT5 inhibitor compound for treating cancer. Hu teaches the success of PRMT5 in cancer therapy and that combinations with PD-L1 therapies such as nivolumab would be successful. Thus, one of ordinary skill in the art would have had a reasonable expectation of success in the combination therapy. In addition, the combination of the two therapies for the very same purpose is prima facie obvious. “[T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 205 USPQ 1069, 1072 (CCPA 1980).
The Supreme Court stated in KSR "if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person's skill." KSR Intern. Co. v. Teleflex Inc., 127 S.Ct. 1727, 1731 (2007).
Because combining the two anticancer therapies is taught by the prior art and such combinations have been shown to be successful, one of ordinary skill in the art would have a reasonable expectation of success in arriving at the combination as in the claimed invention. Thus, one of ordinary skill in the art would have arrived at the invention as claimed before the effective filing date with a reasonable expectation of success.
Response to Remarks - 35 USC § 103
Applicant argues that the claims as amended are to a PRMT5 inhibitor with a PD-1 inhibitor while the cited art teaches a different PD-L1 inhibitor.
This argument is not persuasive because Hu specifically teaches “pharmacological PRMT5 inhibitors with anti- PD-1 therapy results in the inhibition of melanoma growth” (Hu p 10) and “PD-1 expression on tumor-infiltrating lymphocytes interacts with PD-L1 expressed on tumors and/or immune cells in the tumor microenvironment (TME), thus attenuating effector T cell responses and enabling tumors to escape immune attack” addressed via “Anti-PD1 mAb (nivolumab)” (Hu p. 2). Thus, one of ordinary skill in the art would have reasonably considered a combination with anti-PD1 therapy including known ones that address the same corresponding mechanism shown to be effective by Hu.
Applicant argues that the claimed combinations exhibit unexpected synergistic activity as evidenced by Table 1 and Figure 1-16 presented in the remarks and without a supporting declaration. The remarks are not persuasive and are not properly factually supported. MPEP 716.01(c) (“Objective evidence which must be factually supported by an appropriate affidavit or declaration to be of probative value includes evidence of unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.”). Furthermore, the data often appears to be merely additive and not synergistic, i.e., Fig. 16’s compound 7 alone is 27.4%, Pembrolizumab along is 51.3% and the combination is 73.3% whereas additive would be expected to be 78.7%. In addition, Applicant tested only a single second agent in the combination while claim 1 is to all PD-1 inhibitors. Thus, Applicant has not met their burden of establishing an alleged unexpected result commensurate with the scope of the claims.
None of Applicant’s arguments are persuasive and the rejection maintained.
Double Patenting
Claims 1, 10-11, and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 12173002 in view of Hu. Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims the elected species (claim 16) with the same utility and for the same reasons provided in the 35 USC 103 rejection supra renders the instant claims obvious.
Claims 1, 10-11, and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of copending Application No. 18925084 (reference application) in view of Hu. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application claims the elected species (claim 26) with the same utility and for the same reasons provided in the 35 USC 103 rejection supra renders the instant claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 10-11, and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 32 of copending Application No. 19527673 (reference application) in view of Hu. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application claims the elected species with the same utility and for the same reasons provided in the 35 USC 103 rejection supra renders the instant claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 10-11, and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8 of copending Application No. 19539095 (reference application) in view of Hu. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application claims the elected species with the same utility and for the same reasons provided in the 35 USC 103 rejection supra renders the instant claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Remarks - Double Patenting
Applicant argues the claims are nonobvious in the same manner as in the 103 rejection. This argument is not persuasive as detailed above and is maintained.
Conclusion
No claims allowed.
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 ROBERT H HAVLIN whose telephone number is (571)272-9066. The examiner can normally be reached 9am - 6pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney Klinkel can be reached at (571) 270-5293. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626
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