Detailed Action
The present office action is in response to the reply filed on 24 Jun 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 .
Status
Claims 1-2, 4, 6, 9, and 12-13 of the pending application have been examined on the merits. Claims 3, 5, 7-8, 10-11, and 14-24 of the instant application are withdrawn (see “Response to Applicant Elections” below). Acknowledgement is made of the amendments filed 24 Jun 2026.
Priority
Applicants identify the instant application, Serial #: 18/627,032, filed 04 Apr 2024, as a Continuation-In-Part of International Patent Application #: PCT/CN2023/121715, filed 26 Sep 2023, which claims foreign priority from Foreign Application #s: CN202311207394.3, filed 19 Sep 2023, and CN202211211068.5, filed 30 Sep 2022.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 01 Jul 2024 and 11 Mar 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Applicant Elections
Applicant’s election with traverse of Group I, claims 1-13, in the reply filed on 06 May 2026 is acknowledged. Applicant further elected the following species of IN10018 as the FAK inhibitor, D-1553 as the immunogenic cell death inducer, INX0082 as the immune checkpoint inhibitor, and colon cancer as the tumor in the reply filed 24 Jun 2026. The traversal is on the ground(s) that there would not be a serious search or examination burden on the examiner if restriction is not required because a search for one of the groups of inventions would likely result in finding art pertinent to the other group of inventions.
This is not persuasive for the reasons stated on pg. 3 of the office action mailed 24 Apr 2026. Briefly, there is a serious search burden because the groups of inventions have separate classifications and examining each constitutes a serious search burden.
The requirement is still deemed proper and is therefore made FINAL.
A search for the elected composition did not return prior art. Examiner expanded the Markush search to encompass pembrolizumab as the species of anti-PD-1/PD-L1 antibody as found in claim 6. A search for this composition returned prior art.
Claims 3, 5, 7-8, and 10-11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Claims 14-24 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. Election was made without traverse in the reply filed on 24 Jun 2026.
Examiner notes that the relevant anticipation rejection below is based upon art which was found incidental to the search for the elected species. The additional art found is relevant to the claims addressing species which have the same composition as in the claims. This is not indicative that the entire scope of the claims has been examined; however, the following art is being applied in an effort to promote compact prosecution of the case.
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 1-2, 4, 6, 9, and 12-13 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 treating breast cancer, lung cancer, and colorectal cancer by administering a composition comprising a FAK inhibitor, immunogenic cell death inducer, and optionally an immune checkpoint inhibitor to a subject, does not reasonably provide enablement for treating all cancers with the above composition. 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.
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:
the quantity of experimentation necessary,
the amount of direction or guidance provided,
the presence or absence of working examples,
the nature of the invention,
the state of the prior art,
the relative skill of those in the art,
the predictability of the art, and
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:
The nature of the invention, state and predictability of the art, and relative skill of those in the art
The invention relates to methods of treating all cancers by administering a composition comprising a FAK inhibitor, immunogenic cell death inducer, and optionally an immune checkpoint inhibitor to a person in need thereof.
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.); 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, 1997, 278:1041-1042), hereinafter Gura, Johnson et al. (Br J Cancer, 2001, 84:1424-1431), hereinafter Johnson, and Kunnumakkara et al. (Exp Biol Med, 2019, 244:663-689), hereinafter Kunnumakkara.
Gura, cited for evidentiary purposes, teaches that researchers face the problem of sifting through potential anticancer agents to find ones promising enough to make human clinical trials worthwhile and further teach that since formal screening began in 1955, many thousands of drugs have shown activity in either cell or animal models, but only 39 have actually been shown useful for chemotherapy (pg. 1041, first and second paragraph). Also, with regard to unpredictability, Johnson, also cited for evidentiary purposes, teach that the in vivo activity of 39 different agents in a particular histology in a tumor model did not correlate to activity in the same human cancer (pg. 1426, Results). In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. Further, the mode of action of anticancer agents is often unknown or very unpredictable and administration of such agents is often accompanied by undesirable side effects.
Furthermore, with regard to unpredictability, Kunnumakkara, cited for evidentiary purposes, teaches cancer is a group of more than 200 neoplastic diseases caused by diverse deregulated cell signaling cascades (pg. 633, first column); consumption of tobacco and alcohol, obesity, insufficient physical activity, exposure to ultraviolet radiation, and various dietary factors which include insufficient fruit, non-starchy vegetables, and fiber; red/processed meat are predicted to be strongly associated with the risk of diverse cancer types; cancer occurs as a result of the dysregulation of as many as 500 different genes which may happen over a very long duration of time (20–30 years) till the symptoms become apparent (pg. 633, second column). Kunnumakkara further teaches there exists a missing connection between preclinical data and clinical findings; although, a significantly huge amount of money is spent in the pre-clinical settings for target validation and drug optimization, most of the therapies fail in the clinical trials; this can be due to the reason that the models used in the pre-clinical setting are not the adequate ones to effectively mimic human responses (pg. 664, second column); although highly convenient, cancer cell line models are associated with several limitations as well; for example, existence of genomic instability which may result in differences between the original tumor and the respective cell line, culture conditions that can alter the morphology, gene expression pattern, genomic profile, cellular pathways and culture environment from that of the original tumor, loss of natural tumor heterogeneity; the generic transformations that occur upon culturing of the cancer cells are not restored when regrown in vivo; and cancer cells in the in vitro condition grow in absence of stroma which include lymphatic vessels and blood, associated fibroblasts and immune cells, and lack a complex extracellular matrix; therefore, in vitro data often exhibits fundamental mismatch with those obtained from clinical findings and hence this can be regarded as one prime reason behind the failure of novel drug development (pg. 665, last bridge paragraph). Kunnumakkara teaches the foremost shortcomings of the use of animal models are their inability to recapitulate the link between the tumor and its microenvironment completely and the requisite of an immunocompromised host; basically, these animal models do not have the ability to reflect all the features of human cancer impeccably. Kunnumakkara teaches despite the advances in understanding of cancer biology and deriving different novel therapeutic targets, the translation of these understanding into therapies is poor due to higher failure rate (90%). The high failure rate could be due to non-consideration of factors such as clinical translation, drug delivery, drug pharmacokinetics, pre-clinical models, and tumor physiology, which are critical factors.
These articles plainly demonstrate that the art of developing and testing anticancer drugs, particularly for use in humans, is extremely unpredictable, particularly in the case of a single compound or genus of compounds being used to treat any and all cancers.
The breadth of the claims
Claim(s) 1, 2, 4, 6, 9, 12, and 13 are very broad in terms of the type of diseases being treated and the types of compounds administered: claims 1, 2, 4, 6, 9, and 12 are directed to all types of cancers being treated with any composition of FAK inhibitor, immunogenic cell death inducer, and optionally an immune checkpoint inhibitor. Claim 13 claims a very broad list of cancers still being treated with any composition of FAK inhibitor, immunogenic cell death inducer, and optionally an immune checkpoint inhibitor.
The amount of direction or guidance provided and the presence or absence of working examples
The specification provides data that shows the anti-cancer effect of the composition of a FAK inhibitor, immunogenic cell death inducer, and an immune checkpoint inhibitor in breast cancer cells, lung cancer cells, and colorectal cancer cells. Thus, the data provided shows the effect of the claimed composition with very specific cancers, breast cancer, lung cancer, and colorectal cancer.
The specification provides no particular direction or guidance for determining the particular administration regimens (e.g., timing, administration routes, etc.) necessary to treat all of the various cancers encompassed by the claims, particularly in humans. At best, a “therapeutically effective amount” is exemplified as “an amount generally sufficient to produce a beneficial therapeutic effect on a subject” (paragraph [00123]). While experimentation is presented for treatment of breast cancer, lung cancer, and colorectal cancer there is no experimentation or mechanism of action presented or discussed in the specification regarding treatment of the cancers that are not breast cancer, lung cancer, and colon cancer
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 the claimed composition could be predictably used as treatment for all cancers.
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).
As noted above, none of the experimentation provided is drawn to the treatment of a cancer that is not breast cancer, lung cancer, or colon cancer. Determining if any particular claimed compound would treat any particular cancerous disease state 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. This is undue experimentation given the limited guidance and direction provided by Applicants. As noted supra, even in vitro and in vivo assays do not always correlate to efficacy in humans and are not generally predictive of clinical efficacy.
Accordingly, the instant claims do not comply with the enablement requirement of 35 U.S.C. 112(a), 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.
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 13 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 13, the phrase "including" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-2, 4, 6, 9, and 12-13 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2023/009572 (provided in IDS 07/01/24), hereinafter ‘572. ‘572 was published 02 Feb 2023 and has an effective filing date of 27 Jul 2021.
The instant claims are drawn towards a method of treating cancer in a subject by administering a FAK inhibitor, an immunogenic cell death inducer, and optionally an immune checkpoint inhibitor to a subject (claims 1-2, 4, 6, 9, and 13). The claims further timing of administering the composition to simultaneous or sequential administration (claim 12). In the reply filed 24 Jun 2026 applicant elected IN10018 as the species of FAK inhibitor, D-1553 as the species of immunogenic cell death inducer, and INX0082 as the species of immune checkpoint inhibitor. Examiner has expanded the Markush search to include the anti-PD-1 antibody, pembrolizumab as the species of immune checkpoint inhibitor.
‘572 teaches a method of treating cancer by administering a dual RAF/MEK inhibitor in combination with an anti-PD-1 antibody, a KRAS GC12 inhibitor, and optionally a FAK inhibitor (Abstract and paragraphs [0006], [0009], and [00037]). The species of the anti-PD-1 antibody, KRAS GC12 inhibitor, and FAK inhibitor include pembrolizumab (paragraphs [00016] and [00057]), D-1553 (paragraphs [00018] and [00067]), and BI-853520 (paragraphs [00077] and [00079]), respectively. BI-853520 has the same structure as the claimed FAK inhibitor, IN10018. ‘572 teaches that the species of cancer that can be treated includes colon cancer (paragraphs [00086] and [00099]) ‘572 further teaches administering the compositions of the reference simultaneously or sequentially (paragraph [000117]). The reference thus anticipates the instant claims.
Claim(s) 1-2, 4, 6, 9, and 12-13 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2021/154929 (provided in IDS 07/01/24), hereinafter ‘929. The following anticipation rejection below is based upon art which was found incidental to the search for the elected species. The additional art found is relevant to the claims addressing species which have the same composition as the claims. This is not indicative that the entire scope of the claims has been examined; however, the following art is being applied in an effort to promote compact prosecution of the case.
‘929 teaches a method of treating cancer by administering a KRAS GC12 inhibitor selected from ARS-853, ARS-1620, ARS-3248, LY3499446, AMG-510k, and MRTX849, and a FAK inhibitor selected from defactinib, TAE226, IN10018, GSK2256098, PF-03814735, BI-4464, VS-4718, and APG-2449 (Abstract and pg. 2, lines 14-19). ‘929 further teaches that the compounds can be administered simultaneously or sequentially (pg. 29, lines 6-8). Therefore the reference anticipates the instant claims.
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 1-2 and 12-13 are rejected on the ground of anticipatory-type nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 12,257,251. Although the claims at issue are not identical, they are not patentably distinct from each other.
The reference claims a method of treating melanoma having an NRAS mutation by administering an effective amount of BI853520 (claim 1) and further a second therapeutic agent which includes ALK/ROS1 inhibitors (claim 6). Therefore, the reference overlaps with the instant claims.
Claims 1-2, 4, 9, and 12-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 18/674,295 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The reference teaches a method of treating cancer by administering IN10018 and a KRAS inhibitor, which includes D1553. The reference therefore overlaps with the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 4, 9, and 12-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 19/367,527 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The reference teaches a method of treating cancer by administering IN10018 and a KRAS inhibitor, which includes D1553. The reference therefore overlaps with the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 4, 9, and 12-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-11 of copending Application No. 19/606,397 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The reference teaches a method of treating cancer by administering a FAK inhibitor and a KRAS inhibitor. The reference therefore overlaps with the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Wörthmüller et al. (Int J Mol Sci, 2020, 21:9107) is considered pertinent for teaching that BI85320 has only modest single-agent activity and could be explored in combination with other chemotherapies for cancer treatment. Baraibar et al. (Cancers, 2021, 12:6311) is considered pertinent for teaching immunotherapy-based strategies for treating colorectal cancer. Kwan et al. (J Exp Clin Cancer Res, 2021, 41:27) is considered pertinent for teaching KRAS G12C inhibitors in clinical trials. O’Neil et al. (PLoS ONE, 2017, 12:e0189848) is considered pertinent for teaching treatment of colorectal carcinoma by administering pembrolizumab.
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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, Andrew Kosar can be reached on (571) 272-0913. 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.
/J.D.M./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
Prosecution Insights