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
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Terminal Disclaimer
The terminal disclaimer filed on 01/06/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of 18/014156 Application has been reviewed and is accepted. The terminal disclaimer has been recorded.
Election/Restrictions
Claims 1-3, 5 and 11-15 (new claims) are directed to an allowable product. Therefore, pursuant to the procedures set forth in MPEP § 821.04(B), the nonelected inventions are considered for rejoinders.
Claims 4, 6-9, directed to the process of making or using an allowable product, previously withdrawn from consideration as a result of a restriction requirement, Group II-IV hereby rejoined and fully examined for patentability under 37 CFR 1.104. However, Group V (claim 10), directed to the intermediate, is not rejoined herein since the withdrawn claim 10 does not require all the limitations of an allowable product claims. Note that if claims are directed to nonelected invention without traverse that is not eligible for rejoinder, the claim needs to be cancelled before the allowance. See MPEP 821.02.
Because claims 4 and 6-9 previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement among Group I-IV as set forth in the Office action mailed on 06/23/2025 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 4 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Independent claim 4 which is drawn to a process of making recites a borate compound (Formula A), a bromide compound (Formula B), and an intermediate (Formula C). However, the claim does not define the limitations associated with these formulas. For example, are the variables R6, R7, X, and n1 the same as the substituents defined for the Formula II structure in claim 1, or are they different? To render Claim 4 complete and definite, please provide explicit definitions for all variables/limitations used in Formulas A–C, or clearly incorporate by reference the definitions from claim 1.
Notes: Amendments to overcome 112(b) rejection must be supported by the original disclosure; do not introduce new matter. See MPEP 2163-2163.05.
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 7-9 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for a method of inhibiting a kinase BTK or HER2, does not reasonably provide enablement for treatment of a disease state or condition caused by overexpression of BTK kinase or HER2 kinase, namely “an autoimmune disease, inflammatory disease, thromboembolic disease, hypersensitivity, infectious disease, proliferative disorder, a cancer…”. 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/or 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 breadth of the claims: Given BRI, the instant claimed invention is related to the treatment of all disease states or conditions mediated by overexpression of BTK kinase or HER2 kinase.
2) The nature of the invention: The nature of the invention is therefore drawn to the pharmaceutical art. These claims cover diseases that are known to exist and those that may be discovered in the future, for which there is no enablement provided.
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 therapeutic regimen on its face. While a full discussion of each disease which is encompasses by Applicant's claim language will not be given, 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 treatment 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.
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 treating all of disease conditions encompassed by the claimed invention, for instance every inflammatory disease, autoimmune disease, thromboembolic disease, infections disease, proliferative disease, cancer and disease subtypes. No reasonably specific guidance is provided concerning useful therapeutic protocols for said cancers, other than inhibition of BTK or HER2 kinase activity. The latter is corroborated by tables in the specification on pages 128-133 The disclosure does not provide how the in vitro data correlates to the treatment 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 treated by the compounds encompassed in the instant claims, with no assurance of success.
Furthermore, there is no evidence of record, which would enable the skilled artisan in the identification of the people who have the potential of becoming afflicted with the numerous diseases/disorders or conditions claimed herein. That a single compound can be used to treat all diseases/disorders and conditions embraced by the claim is an incredible finding for which Applicant has not provided supporting evidence. Applicant has not provided any competent evidence or disclosed tests that are highly predictive for the pharmaceutical use for treating any or all of the diseases/disorders or conditions by administering the instant claimed compound.
Allowable Subject Matter
Claims 1-3, 5-6 and 11-15 are allowed.
The following is a statement of reasons for the indication of allowable subject matter:
WO 2021/136219 is the closest prior art of record. The main difference between WO’219 and the instantly claimed compounds by the formula II relates to the fact that the prior art compounds contain -O-linker for the present -X- position where X is selected from
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, wherein R9 and R13 are independently selected from the fluorine, trifluoromethyl or hydroxyl. There is no teaching or suggestion in WO’153 for replacing -O-link with fluorine, trifluoromethyl or hydroxyl, furthermore modification at R7 position with substituted or unsubstituted aryl, substituted or unsubstituted pyridyl wherein the substituent is independently selected from the group consisting of halogen, hydroxyl, amino, cyano, alky, heteroalkyl, cycloalkyl and heterocycloalkyl, wherein the number of the substituent is an integer between 0 and 5.
Notes to Applicants
Multiple calls and voicemail messages were left for Mr. Yue (Robert) Xu on 02/23 and 03/03/2026 to discuss a possible claim amendment that could place the instant application in condition for allowance. No response has been received. To avoid further delay in prosecution, the applicant’s representative is strongly encouraged to contact the undersigned at your earliest convenience to discuss next steps.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion
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/BRIAN-YONG S KWON/
Supervisory Patent Examiner, Art Unit 1613