DETAILED ACTION
This office action is in response to the Applicant’s filing dated June 12th, 2026.
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 19/094,924 filed on March 30th, 2025; a CON of PCT/CN2023/122129 filed on September 27th, 2023; and claims benefit of foreign priority of CN202311247776.9 filed on September 26th, 2023, CN202310721348.9 filed on June 16th, 2023, CN202310258788.5 filed on March 16th, 2023, CN202310080287.2 filed on January 17th, 2023, CN202211583282.3 filed on December 9th, 2022 and CN202211208795.6 filed on September 30th, 2022. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Status of Claims
Claims 24-49 are pending in the instant application. Acknowledgement is made of Applicant's remarks and amendments filed on June 12th, 2026. Acknowledgement is made of Applicant's amendment of claims 26 and 39; and addition of new claims 46-49.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on June 12th, 2026 is acknowledged.
Claims 43-45 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on June 12th, 2026.
Applicant's election with traverse of Example 274 shown below in the reply filed on June 12th, 2026 is acknowledged:
PNG
media_image1.png
551
588
media_image1.png
Greyscale
The traversal is on the ground(s) that the requirement is prohibited under 37 C.F.R. § 141. This is not found persuasive because 37 C.F.R. § 141 is directed to national stage applications filed under 35 U.S.C. § 371, whereas the instant application is filed under 35 U.S.C. § 111(a) and thus is not applicable.
The requirement is still deemed proper and is therefore made FINAL.
Claims 38-39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the election requirement in the reply filed on June 12th, 2026.
A prior art search was conducted for the elected species Example 274.
No prior art was found.
Therefore, the Examiner expanded search to encompass the full scope of Formula (I) wherein k is 0 and Z is C.
No prior art was found.
Claims 24-42 and 46-49 are directed to a product that cannot be stated is allowable in its entirety, due to the unclear metes and bounds discussed in the 35 USC § 112(b) rejection below. However, in the interest of compact prosecution, pursuant to the procedures set forth in MPEP § 821.04(B), claims 43-45, directed to the process of making or using a product, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action mailed on April 16th, 2026 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(b)
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 24 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.
Regarding claim 24, there is no definition recited for the variables “k” or “Z” of Formula (I), thus rendering the metes and bounds of the claim unclear.
Claim Rejections - 35 USC § 112(a)
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 43-45 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 antitumor activity against KRAS G12D mutation mediated pancreatic cancer and colorectal cancer cells in vivo in Examples 7-8 on pages 443-445; as well as colorectal cancer, gastric cancer and pancreatic cancer in vitro in Examples 5 and 9 on pages 442-443 and 445-447; does not reasonably provide enablement for treating or reducing the risk of developing any KRAS G12V or G12D mutation mediated disease in a subject. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. This is a scope of enablement rejection.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
3- the presence or absence of working examples,
4- the nature of the invention,
5- the state of the prior art,
6- the relative skill of those in the art,
7- the predictability of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
1. The nature of the invention and breadth of the claims
The invention relates to a method of treating a subject having, or reducing the risk of development in a subject susceptible to, a disease mediated by KRAS G12V or G12D mutation.
Claims 43-45 are directed to a method of treating a subject having, or reducing the risk of development in a subject susceptible to, a disease mediated by KRAS G12V or G12D mutation comprising administering to the subject a compound of Formula (I). Thus, the claims are extremely broad with regards to the diseases to be treated as well as the possible compounds that can be utilized.
2. The state and predictability of the art, and relative skill of those in the art
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using Applicant’s invention would generally be a physician with a M.D. degree and several years of experience.
The factor is outweighed, however, by the unpredictable nature of the art. It is well established that “the scope of enablement varies with the degree of unpredictability of the factors involved” and physiological activity is considered to be an unpredictable factor. See In re Fisher, 166 USPQ 18, at 24 (In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved); Nationwide Chemical Corporation, et. al. v. Wright, et. al., 192 USPQ 95 (one skilled in chemical and biological arts cannot always reasonably predict how different chemical compounds and elements might behave under varying circumstances); Ex parte Sudilovsky 21 USPQ2d 1702 (Applicant’s invention concerns pharmaceutical activity. Because there is no evidence of record of analogous activity for similar compounds, the art is relatively unpredictable); In re Wright 27 USPQ2d 1510 (the physiological activity of RNA viruses was sufficiently unpredictable that success in developing specific avian vaccine was uncertain).
As illustrative of the state of the art, the examiner cites Gura et al (Science, New Series, (1997), 278(5340), 1041-1042), cited for evidentiary purposes, teaches that researchers face the problem of sifting through potential anticancer agents to find ones promising enough to justify human clinical trials. The reference further teaches that, since formal screening began in 1955, many thousands of drugs have shown activity in cell or animal models, but only 39 have actually been useful for chemotherapy (page 1041, first and second paragraphs). With regard to unpredictability, Johnson et al (British Journal of Cancer, (2001), 84(10), 1424-1431), also cited for evidentiary purposes, teaches that the in vivo activity of 39 different agents in a particular histology in a tumor model did not correlate with activity in the same human cancer (page 1426, Results). The examiner further cites Pang et al (Small GTPases, (2016), 8(4), 212-219), also cited for evidentiary purposes, who teaches that “Although KRAS mutation is prevalently present in pancreatic, colon and lung cancers, the hot mutations and mutation-specific signaling pathways of KRAS in these cancer types are dramatically different. Not all mutant KRAS proteins affect patient survival or downstream signaling in a similar way. Most mutations of KRAS occur at codons 12 and 13, and the KRASG12C mutation is the most common mutation in lung cancer, which is quite different from other cancer types. Difference in mutation frequency may reflect different biological characteristics of a mutant protein. For example, KRASG12C and KRASG12V mutations in lung adenocarcinoma preferentially activate the RalGDS pathway, whereas KRASG12D prefers the MAPK and PI3K pathways. The heterogeneous behavior of mutant KRAS proteins suggests that therapeutic interventions may need to take into account the specific mutant KRAS expressed by the tumor” (page 215, right column, first full paragraph).
“The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability of the art” In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970).
Accordingly, the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statutory requirements. Furthermore, the mechanism of action of anticancer agents is often unknown or highly unpredictable, and the administration of such agents is frequently accompanied by undesirable side effects.
3. The amount of direction or guidance provided and the presence or absence of working examples
The specification provides data for antitumor activity against KRAS G12D mutation mediated pancreatic cancer and colorectal cancer cells in vivo in Examples 7-8 on pages 443-445; as well as colorectal cancer, gastric cancer and pancreatic cancer in vitro in Examples 5 and 9 on pages 442-443 and 445-447, but it is not sufficient to provide support for the full scope of compounds encompassed by the claims or for the full scope of all diseases mediated by KRAS G12V or G12D mutation.
The specification provides no particular direction or guidance for determining the particular administration regimens (e.g. timing, administration routes, etc) necessary to treat diseases mediated by KRAS G12V or G12D mutation encompassed by the claims, particularly in humans. At best, an "effective amount" is exemplified as a dosage sufficient to provide treatment for cancer.
4. The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed supra) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that any compound of Formula (I) could be predictably used as treatment for all diseases mediated by KRAS G12V or G12D mutation; or used to reduce the risk of development of all diseases mediated by KRAS G12V or G12D mutation in a subject.
Genentech Inc. vs. Nova Nordisk states, "[A] patent is not a hunting license. It is not a reward for a search but a 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" (42 USPQ 2d 1001, Fed. Circuit 1997). A review of the state of the art fails to reveal the mechanism of action or experimental data regarding the use of any claimed compounds to treat, or reduce the risk of developing, all diseases mediated by KRAS G12V or G12D mutation. Determining if any particular claimed compound would treat, or reduce the risk of developing, a disease mediated by KRAS G12V or G12D mutation would require synthesis of the compound, formulation into a suitable dosage form, and subjecting it to clinical trials or to testing in an assay known to correlate to clinical efficacy of such treatment. As noted in supra, even in vitro and in vivo assays do not always correlate to efficacy in humans and are not generally predictive of clinical efficacy. This is undue experimentation given the limited guidance and direction provided by Applicants.
Accordingly, the inventions of instant claims 43-45 do not comply with the scope of enablement requirement of 35 U.S.C 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success.
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 24-42 and 46-49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 27-34 of Application No. 19/094,924 (reference application has been allowed, US Patent number not yet issued).
Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application’s claimed compounds substantially overlap with the instantly claimed core structure and substituents. Specifically, the claimed compounds of the reference application read on instantly claimed Formula (I) wherein B is
PNG
media_image2.png
111
70
media_image2.png
Greyscale
; wherein M is N; wherein R2 is H or C1 alkoxy; wherein R3 is F; wherein G is N; wherein R1 and R1’ together form an intracyclic bridging -(CH2)2-; wherein Y is O; wherein k is 0; wherein Z is C; wherein R11 is C1 alkyl or CD3; wherein m is 2, and the two R12 attached to the same C atom that is at the Z variable position forms =C(Rc)2, and Rc is H or F; wherein R13 is C1 alkyl; wherein t is 2; and wherein each R14 is H. The differences of the instantly claimed formula’s substituents represent routine structural variations that do not render the claimed subject matter patentably distinct in view of the substantial overlap in core structure, substituents and disclosed therapeutic use.
Conclusion
Claims 24-49 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTOPHER L JOHNSON whose telephone number is (571)272-1672. The examiner can normally be reached Monday - Friday 08:00AM - 5:00PM EST with Flex on Fridays.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Renee Claytor can be reached at (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/C.L.J./Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
Prosecution Insights