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
The instant application is the national stage entry of PCT/CN2023/080261 filed 08 March 2023. Acknowledgement is made of the Applicant's claim of foreign priority based on an application filed in CN 2022210234527 on 10 March 2022.
Election/Restrictions
Applicant’s election of Group I with traverse in the reply filed on 08/24/2026 is acknowledged. Applicant traversed that compounds disclosed in WO’952 differ from the claimed crystal form A of a compound of formula (I). This argument is found persuasive. Accordingly, the restriction between Group I and II is withdrawn. Claims 1-13 are pending for the examination.
Recommendation
For purpose of clarity, claim 10 is recommended to be amended to insert a “wherein” clause before the recitation of “the disease is…”.
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 10-13 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 a method of treating a liver cancer, prostate cancer, pancreatic cancer or T-cell acute lymphoblastic leukemia, does not reasonably provide enablement for methods of preventing said diseases in a subject in need thereof. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”. These factors include 1) the breadth of the claims, 2) the nature of the invention, 3) the state of the prior art, 4) the level of one of ordinary skill, 5) the level of predictability in the art, 6) the amount of direction provided by the inventor, 7) the existence of working examples, and 8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
1) The bread of the claims: The claimed invention is drawn to a prevention of a liver cancer, prostate cancer, pancreatic cancer or T-cell acute lymphoblastic leukemi9a. In the absence of an explicit definition in Applicant’s specification, the claims are given their broadest reasonable interpretation. In this case, preventing a disease, as recited in base claim 10, is taken as meaning administering the therapy to a patient not exhibiting any signs of the disease, in such a way as to completely avoid any occurrence whatsoever of the disease. Treatments that arrest the progress of an existing disease or reduce the severity of future illness without fully eliminating said condition, are not seen to be preventative.
2) The nature of the invention: The nature of the invention is therefore drawn to the pharmaceutical art.
3) The state of the prior art and 4) the level of predictability in the art: The state of the prior art is that the pharmacological art involves screening in vitro and in vivo to determine which compounds exhibit the desired pharmacological activities (i.e. what compounds can treat which specific disease by what mechanism). There is no absolute predictability even in view of the seemingly high level of skill in the art. The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any prophylactic regimen on its face. The following examples teach that the state of the prior art with respect to the claimed diseases has not advanced to the point of being predictive of the prevention of the breadth of diseases instantly claimed.
For example, it is also known (see Golub et al., Science, Vol. 286, October 15, 1999, pages 531-537) in the current art that the challenge of cancer treatment has been to target specific therapies to pathogenetically distinct tumor types, to maximize efficacy and minimize toxicity. Cancer classification has been based primarily on morphological appearance of the tumor yet tumors with similar histopathological appearance can follow significantly different clinical courses and show different responses to therapy (Golub et al., Science, Vol. 286, October 15, 1999, pages 531-537). There is no absolute predictability even in view of the seemingly high level of skill in the art. Even today, choosing an appropriate model that best imitates the given tumor entity is a significant challenges for researchers (Antunes et al., Bioengineering (Basel), 2022, Apr 7;9(4):166, pages 1-15, conclusion). The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any therapeutic regimen on its face. That a single class of compounds can be used to treat all cancers embraced by the claims is an incredible finding for which Applicants have not provided supporting evidence and/or enablement support.
It is generally known in the current state of art that a cure for the liver cancer, prostate cancer and pancreatic cancer remain still elusive (“The 10 deadliest cancers, and why there’s no cure”, Live Science, Online article, 2025).
5) The level of one of ordinary skill: The artisans using applicant's method would be a collaborative team of synthetic chemists and/or health practitioners, possessing commensurate degree level and/or skill in the art, as well as several years of professional experience. The level of skill in the art is high; however, due to the unpredictability in the pharmaceutical art, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro or in vivo screening to determine which compounds exhibit the desired pharmacological activity and which diseases would benefit from this activity.
6) The amount of direction provided by the inventor and 7) working examples: The specification provides no direction or guidance for preventing disease conditions encompassed by the claimed invention. The latter is corroborated by Experimental data in the specification on pages 21-27. The disclosure does not provide how the in vitro data correlates to the prevention of the assorted disorders of the instant claims. Pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, "the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved." See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
8) The quality of experimentation necessary: A person having ordinary skill in the art at the time the invention was made would be faced with an undue amount of experimentation to use the pharmaceutic al compositions for the full scope of the claimed intended uses.
Genentech Inc. v. Novo Nordisk A/S (CA FC) 42 USPQ2d 1001, states that "a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and "patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable".
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to test which diseases can be prevented by the compounds encompassed in the instant claims, with no assurance of success.
Applicant has not provided any competent evidence or disclosed tests that are highly predictive for the pharmaceutical use for preventing said disease conditions by administering the instant claimed compound.
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 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of US Patent 12435101, and further in view of Vippagunta et al. (“Crystalline Solids”, Advanced Drug Delivery Reviews, 48 (2001), 3-26, hereinafter “Vippagunta”).
Although the claims at issue are not identical, they are not patentably distinct from each other because one having ordinary skill in the art would have “at once envisage” the instant compound
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from the general formula (I), (I-1), (I-3) depicted in claims 1-3 by plugging T is N; R1 and R2 are each independently H or F; and R3 and R4 are each independently H. For instance, the referenced claim 10 discloses identical compound. Specifically, claim 1 of ‘101 claims a compound having a structure that overlaps with the structure (I) recited in present claim 1 where it defines variables T as N and R1, R2, R3, R4 as independently H or F. Claims 11-13 of ‘101 claim methods of treating liver cancer which are equivalent to those recited in present claims 10-13.
Although the instant claims differs from the patented claims in the recitation of particular crystalline form A, as defined by characteristic X-ray powder diffraction peaks in claims 1-9, that are measured by differential scanning calorimetry or thermogravimetric analysis technique, it would therefore have been obvious to a person having ordinary skill in the art at the time the invention was made to select the claimed crystalline form A because salt screening and polymorph screening are routine in pharmaceutical development and would have been expected to yield predictable results. The claimed crystalline forms are merely expected variants of the known active ingredient, and the possibility that an active pharmaceutical ingredient may exist in different polymorphic forms with differing physical properties would have been well within the ordinary skill of the artisan, in absent evidence to the contrary.
Vippagunta is provided as a supplemental reference to demonstrate that polymorphs, solvates, and crystalline forms of active pharmaceutical ingredients are well known in the art, and that routine screening and characterization techniques are commonly used to identify crystalline forms having desirable properties, such as improved stability, handling, formulation, and bioavailability. See Vippagunta, abstract; pages 5-6 and 11-14.
Vippagunta further teaches that polymorph screening and solid-state characterization are routine in pharmaceutical development, and that crystalline forms may be identified and distinguished by analytical techniques including X-ray powder diffraction using CuKa Radiation, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and others (pages 5-7, 11-14).
In particular, the selection of a polymorph characterized by a specific XRPD peak or combination of peaks would have been an expected result of routine crystallization and screening efforts. Once the compound itself was known, one of ordinary skill in the art would have had a reasonable expectation of success in obtaining a crystalline form exhibiting a desired diffraction pattern through conventional polymorph screening, crystallization solvent selection, temperature variation, evaporation conditions, seeding, and other routine solid-state development techniques. Therefore, the claimed polymorph defined by a particular X-ray powder diffraction peak pattern would have been obvious to prepare and isolate.
In addition, the U.S. Patent Office is not equipped with analytical instruments to test prior art compositions for the infinite number of ways that a subsequent applicant may present previously unmeasured characteristics. When as here, the prior art appears to contain the exact same ingredients and applicant's own disclosure supports the suitability of the prior art composition as the inventive composition component, the burden is properly shifted to applicant to show otherwise.
Conclusion
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/BRIAN-YONG S KWON/Supervisory Patent Examiner, Art Unit 1613
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