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 .
Detailed Action
Request for Continued Examination
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/26/2026 has been entered.
Rejoinder
Claims 1-2 and 33 are found allowable.
Claims 1-2 and 33 directed to an allowable product. Pursuant to the procedures set forth in MPEP § 821.04(B), claims 3-12, directed to the process of making or using an allowable product, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action mailed on 10/31/2024 is hereby withdrawn.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 Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable.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.
Status of claims
Claims currently pending and under examination are claims 1-12 and 33.
Response to Remarks
In view of the arguments made in the remarks submitted 05/26/2026 and the amendments made 05/26/2026, the 103 rejection made in the prior office action has been withdrawn.
New Rejection
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 3-12 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 ameliorating breast cancer, pancreatic cancer, and colorectal cancer using the claimed compound with nivolumab, does not reasonably provide enablement for amelioration or prevention of all proliferative disorders using the compound and pembrolizumab or other anti-PD-1 antibodies. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The following Wands factors have been considered if not explicitly stated: (A) The breadth of the claims, (B) The nature of the invention, (C) The state of the prior art, (D) The level of one of ordinary skill, (E) The level of predictability in the art, (F) The amount of direction provided by the inventor, (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Breadth of the claims
Claim 3 states “A method of treating a proliferative disease or disorder associated with Wnt pathway in a subject, the method comprising administering a pharmaceutical combination according to claim 1 to the subject.”
The terms “proliferative disease or disorder associated with Wnt pathway” is not defined (See 112(b) rejection below).
The term “treating” is defined as “ameliorating the disease or disorder [e.g. slowing or arresting or reducing the development of the disease or at least one of the of the clinical symptoms thereof), to preventing or delaying the onset or development of progression of the disease or disorder.” Therefore, “treating” includes prevention.
Nature of the invention
The invention is a clinical method.
State of the prior art
The art does not explicitly teach a method of treating an individual in need of treatment comprising administering the combination of the claimed compound and either nivolumab or pembrolizumab. The claimed compound is known within the art, but the synergistic effect combined with nivolumab is not explicitly taught.
There is nothing within the art that would indicate the combination or even the compounds alone are effective as preventative medication.
Ho (Bioorganic & Medicinal Chemistry Letters Vol. 25, Iss. 23, 2015, of the record) discusses the efficacy of ETC-159 against specific tumor cells. Ho on p. 5475, sequential para. 3 states “The authors have demonstrated that ETC-159 is orally bioavailable and inhibits the growth of MMTV-Wnt1 tumors [breast cancer] effectively…ETC-159 was also shown to be remarkably efficacious in treating preclinical models of genetically defined cancers, in particular pancreatic cancer with RNF43 loss of function mutation and in colorectal cancers with RSPO translocation.”
Guidance and working examples
The instant specification only contemplates administration of the instant compound (herein after ETC-159) with pembrolizumab as discussed in examples 3-4, p. 20-24. The specification on p. 21, states “A 3+3 dose escalation study of compound A with the standard dose of pembrolizumab will first be tested…”.
The affidavit submitted 12/03/2025 discloses the effects of ETC-159 with nivolumab. Data discussed in the prior action is repeated here.
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The above information shows a synergistic effect upon combining administration of ETC-159 and nivolumab against microsatellite stable (MSS) colorectal cancer.
Additionally, the instant specification in discussion of figures 1 and 2 (p. 3, sec. Brief Description of Drawings) indicates that the applicant does not know the specific cancer against which the compounds are being tested. The specification states “patient with unknown primary tumor (presumed to be cholangiocarcinoma)…”. Therefore, the only example indicating efficacy is found within the affidavit provided.
Level of predictability
The level of predictability within the art is null considering that the combination method is not explicitly taught. ETC-159 and pembrolizumab are also known, but their combination to treat proliferative diseases is not well studied. Additionally, the instant specification only provides one example against an unknown tumor type. The affidavit provided only provided one example of efficacy against singular cancer type. The single disclosure does not enable the claimed method for the entire genus of “proliferative diseases or disorders”.
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.
Claims 3-12 are 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.
Indefiniteness – proliferative disease or disorder
Claim 3 claims a method for treating a “proliferative disease or disorder associated with Wnt pathway”.
The term “proliferative disease or disorder associated with Wnt pathway” is not defined within the specification. The term “proliferative disease or disorder” is also not defined. Applicant lists a non-limiting embodiments of “proliferative disease or conditions” starting on p. 10, l. 17. Additionally, there is nothing within the specification that would allow one of ordinary skill to determine whether a disease or disorder is associated with Wnt. Therefore, the limitation “proliferative disease or disorder associated with Wnt pathway” is indefinite.
As claims 7-12 are dependent on claim 3, they are also rejected.
Subject
Claim 3 is drawn to a method of treatment comprising administering a pharmaceutical combination to a subject. The claim does not indicate whether the subject is in need of treatment. The instant specification on p. 9, l. 12-14 defines “subject” but also states “[Subject] may be a human who has been diagnosed and is in the need of treatment for a disease or disorder, as disclosed herein.” Therefore, the specification is non-limiting and the broadest reasonable interpretation includes subjects who may or may be in need of treatment. Considering the ambiguity, one of ordinary skill would not know the metes and bounds of the claim.
Examiner suggests adding “in need thereof” or similar claim language to the claims.
As claims 4-12 are dependent on claim 3, they are also rejected.
Therapeutically effective amount
Claim 3 states “the method comprising administering a pharmaceutical combination according to claim 1 to the subject.” Neither claim 1 or claim 3 indicate an any amounts of the combination that would be therapeutically effective for treating the disease or disorder. Claims 11 and 12 give doses.
Examiner recommends adding claim language that would indicate an effective amount of the combination is administered.
As claims 4-10 are dependent on claim 3, they are also rejected.
Conclusion
Claims 1-2 and 33 allowed.
Claim 3-12 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LUISALBERTO GONZALEZ whose telephone number is (571)272-1154. The examiner can normally be reached M-F 8:30-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LUISALBERTO GONZALEZ/Examiner, Art Unit 1624
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