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 .
Acknowledgments and Claim Status
The Examiner acknowledges receipt of the amendment filed 7/29/2026 wherein claims 1, 3, 5, 6, 8, 9, 11, 15-21, 23, 26-36, 38, 39, 41-43, 46-50, 52-72, and 76-81 were canceled. The amendment filed 7/29/2026 is a duplicate of that filed 2/10/2026. In addition, the Examiner acknowledges receipt of the amendments filed 8/26/2022 and 4/26/2023.
Note(s): Claims 2, 4, 7, 10, 12-14, 22, 24, 25, 37, 40, 44, 45, 51, 73-75, and 82 are pending.
Priority
This application is a 371 of PCT/US2021/019989 filed 2/26/2021 and
PCT/US2021/019989 claims benefit to PRO 62/982,561 filed 2/27/2020.
Note(s): The earliest effective filing date is 2/27/2020 as the pending application is fully supported in the provisional application.
Claim Interpretation
Independent claim 2 is directed to a method for treating a subject for an APC-deficient cancer and/or constitutively active WNT signaling, the method comprising providing to the subject a pharmaceutical composition comprising an effective amount of an inhibitor of (a) tryptophan 2,3- dioxygenase (TDO2) or (b) a cytokine activated by TDO2 activity or a receptor thereof.
Independent claim 51 is directed to a method for identifying a cancer as being sensitive to TDO2 inhibition, the method comprising: (a) obtaining cancer cells from a biological sample from a subject; (b) detecting a deficiency in an APC gene or detecting a WNT activating mutation in the cancer cells; and (c) identifying the cancer as being sensitive to TDO2 inhibition based on (b).
Independent claim 75 is directed to a method for treating cancer in a subject comprising determining whether the cancer has an APC mutation and: (a) if the cancer has an APC mutation, providing to the subject an effective amount of an inhibitor of (ii) TDO2 or (ii) a cytokine activated by TDO2 activity; and (b) if the cancer does not have an APC mutation, providing to the subject an effective amount of an alternate therapy.
Applicant’s Election
Applicant's election without traverse of Group I (pending claims 2, 4, 7, 10, 12-14, 22, 24, 25, 37, 40,44, 45, 73, 74, and 82) filed 7/29/2026 is acknowledged. The restriction requirement is still deemed proper and is therefore made FINAL.
Applicant elected the following species for initial examination: TDO2 inhibitor (PF06845102/EOS200809); APC mutation/constitutive WNT signal subject is being treating (subject is being treated for both of APC deficiency and constitutive WNT signaling); whether cancer immunotherapy also occurs and what the immunotherapy comprises (no immunotherapy was elected; thus, none is present); if additional therapy that is present and what the additional therapy entails (no additional therapy was elected; thus, none is present); if an additional inhibitor is present and what the inhibitor is (no additional inhibitor was elected; thus, no additional inhibitor is present).
Pending claims 2, 4, 7, 10, 12, 22, 24, 25, and 73 read on the elected species. The Examiner and Applicant are in agreement that claims 2, 4, 7, 10, 12, 22, 24, 25, and 73 read on the elected species. Initially, Applicant’s elected species was search. Since prior art was found to elect the species, the search was not further extended.
Withdrawn Claims
Claims 13, 14, 37, 40, 44, 45, 51, 74, 75, and 82 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention/species.
Information Disclosure Statements
The information disclosure statements filed 4/14/2026; 9/3/2024; 2/12/2024; and 12/27/2022 were considered.
Written Description Rejection
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 2, 4, 7, 10, 12, 22, 24, 25, and 73 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Applicant is reminded that an inventor is entitled to a patent to protect his work only if he/she produces or has possession of something truly new and novel. The invention being claimed must be sufficiently concrete so that it can be described for the world to appreciate the specific nature of the work that sets it apart from what was before. The inventor must be able to describe the item to be patented with such clarity that the reader is assured that the inventor actually has possession and knowledge of the unique composition that makes it worthy of patent protection. The pending application does not sufficiently describe the invention as it relates to: (1) APC deficient cancers other than colorectal, breast, prostate, lung, head and neck squamous cell carcinoma, and sarcoma; (2) constitutive active WNT signaling other than those comprising constitutively active beta catenin; and (3) inhibitors other than PF06845102/EOS200809, 680C91, LM10, HTI-1090, DN1406131, RG70099, EPL-1410, CB548, CMG017, CXCL5, CXCL7, CSF3, CXCR2, CXCL2, CXCL10, CCL2, and CXCL1. Thus, what the reader gathers from the instant application is a desire/plan/first step for obtaining a desired result. While the reader can certainly appreciate the desire for achieving a certain end result, establishing goals does not necessarily mean that an invention has been adequately described.
While compliance with the written description requirements must be determined on a case-by-case basis, the real issue here is simply whether an adequate description is necessary to practice an invention described only in terms of its function and/or based on a disclosure wherein a description of the components necessary in order for the invention to function are lacking. In order to satisfy the written description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. In other words, the specification should describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that the inventor created what is the claimed. Thus, the written description requirement is lacking in the instant invention since the various terms set forth above are not described in a manner to clearly allow persons of ordinary skill in the art to recognize that Applicant invented what is being claimed.
112 Second Paragraph Rejections
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 2, 4, 7, 10, 12, 22, 24, 25, and 73 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.
Claims 2, 4, 7, 10, 12, 22, 24, 25, and 73: Independent claim 2 is ambiguous for the following reasons. According to MPEP 2173.05(h), while a Markush grouping may include a large number of alternatives, and not necessarily be indefinite under 35 USC 112(b), in certain circumstances, a Markush group may be so expansive that a skilled artisan cannot determine the metes and bounds of the claimed invention. In the pending claims, the invention is directed to treating a subject for any APC-deficient cancer and constitutively active WNT signaling. The method comprises administering a pharmaceutical composition comprising (1) any possible inhibitor of tryptophan 2,3-dioxygenase (TDO2), (2) any possible inhibitor of a cytokine that is activated by TDO2 activity, and (3) any possible inhibitor of a cytokine activated receptor.
Thus, independent claim 2 encompasses multiple Markush groups and subgroups thereof. As a result, pending claim 2 encompasses a massive number of distinct alternative members such that one skilled in the art cannot determine the metes and bounds of the claim. Hence, due to an inability to envision the various possible APC deficient cancers, the constitutively active WNT signaling, the inhibitors of TDO2, the inhibitors of cytokine active by TDO2, and inhibitors of cytokine activated by receptors and combinations thereof encompassed all of the Markush groups, independent claim 2 is deemed to be vague and indefinite.
Since claims 4, 7, 10, 12, 22, 24, 25, and 73 depend upon independent claim 2 for clarity, those claims are also vague and indefinite.
Claim 4: The claim is ambiguous because it is unclear what mutation(s) Applicant is asserting to be present in the subject.
Claim 12: The claim is ambiguous because it is unclear what portion of the parent structure (PF068684545102/EOS200809, 680C91, LM10, HTI-1090, DN1406131, RG70099, EPL-1410, CB548, and CMG017) is present in the derivative to generate an effective inhibitor that is compatible with the pending invention.
102 Rejection
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.
Claims 2, 4, 7, 10, 12, 22, 24, 25, and 73 are rejected under 35 U.S.C. 102(a)(1) as being anticipate by Crosignani et al (US Patent No. 9,758,505) as evidence by Schramme et al (Cancer Immunol. Res., 2020, Vol. 8, pages 32-45).
Note(s): Both the Examiner and Applicant are in agreement that claims 2, 4, 7, 10, 12, 22, 24, 25, and 73 read on the elected species.
Claim 2 is directed to a method for treating a subject for an APC-deficient cancer and/or constitutively active WNT signaling, the method comprising providing to the subject a pharmaceutical composition comprising an effective amount of an inhibitor of (a) tryptophan 2,3- dioxygenase (TDO2) or (b) a cytokine activated by TDO2 activity or a receptor thereof.
Claim 4 is directed to the method of claim 2 wherein the APC-deficient cancer is a cancer that comprises cancerous cells having an APC mutation.
Claim 7 is directed to the method of claim 2 wherein inhibitor is an inhibitor of the expression or activity of TDO2.
Claim 10 is directed to the method of claim 2 wherein the inhibitor is an siRNA, an shRNA, an antisense oligonucleotide, a small molecule inhibitor, an antibody, or an antibody-like molecule.
Claim 12 is directed to the method of claim 10 wherein the inhibitor is PF06845102/EOS200809, 680C91, LM10, HTI-1090, DN1406131, RG70099, EPL-1410, CB548, CMG017, or a derivative thereof.
Claim 22 is directed to the method of claim 2 wherein the cancer has an increased expression of TDO2 relative to a control or reference sample and wherein the control or reference sample is a biological sample from a healthy subject.
Claim 24 is directed to the method of claim 2 wherein the cancer comprises constitutively active WNT signaling.
Claim 73 is directed to the method of claim 2 wherein the constitutively active WNT signaling comprises a constitutively active 3-catenin.
Crosignani et al is directed to pharmaceutical compositions having Formula I
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that are used for the treatment of cancer (see entire document, especially, abstract). In addition, it is disclosed that the TDO2 inhibitors are administered to mammalian subjects having a condition or disease wherein it is desirable to modulate (e.g., decrease levels of TDO2) including cancer (column 3, lines 65). In particular, Crosignani et al disclose Compound 87,
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(column 73), which is Applicant’s elected species.
In the biological examples to assay TDO2 enzymatic activities for their ability to inhibit the enzymatic activity of human TDO2 in A172 cells which are derived from human brain glioblastoma cells (column 180, lines 21-53; column 182, lines 44-61; column 183, lines 10-60, especially, line 50 which contains data for Compound 87).
Schramme et al (Cancer Immunol. Res., 2020, Vol. 8, pages 32-45) is made of record as an evidentiary reference for the following reasons. (1) The document discloses the structure of PF06845102/EOS200809 (see excerpt below) on page 35, Table 1. PF06845102/EOS200809 is Applicant’s elected species which is Compound 87 in Crosignani. (2) In addition, in Table 1, it is disclosed that the enzymatic activity is evaluated in the cell line A172 human cells. A172 cells are the same cells used in Crosignani et al with Compound 87 (Applicant’s elected inhibitor).
Schramme et al, page 35, Table 1
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Thus, both Applicant and Crosignani et al disclose a method of treating an APC deficient cancer (human brain glioblastoma) using the inhibitor PF06845102/EOS200809,
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(Compound 87 in Crosignani et al). In addition, since both Applicant and Crosignani et al disclose the same inhibitor used for treatment of cancer and claims 2, 4, 7, 10, 12, 22, 24, 25, and 73 read on Applicant’s elected species, those same claims also read on the invention of Crosignani et al. Hence, the inventions disclose overlapping subject matter.
103 Rejection
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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 2, 4, 7, 10, 12, 22, 24, 25, and 73 are rejected under 35 U.S.C. 103 as being unpatentable over Crosignani et al (US Patent No. 9,758,505) as evidence by Schramme et al (Cancer Immunol. Res., 2020, Vol. 8, pages 32-45).
Claim 25 is directed to the method of claim 2 wherein the cancer is colorectal cancer, breast cancer, prostate cancer, lung cancer, head and neck squamous cell carcinoma, or sarcoma.
Crosignani et al renders obvious the limitations of claims 2, 4, 7, 10, 12, 22, 24, 25, and 73 as detailed supra (see 102 rejection above). However, while the document specifically performs analysis of glioblastoma (see column 182, line 44 through column 183, line 50; data for Compound 87 is disclosed in the table), the document does not disclose Compound 87 (Applicant’s elected species) use with various other cancers. But Crosignani et al disclose that the compounds therein may be used for treating cancers such as bladder, hepatocarcinoma, melanoma, mesothelioma, neuroblastoma, sarcoma, breast, leukemia, renal, colorectal, head and neck, lung, brain, glioblastoma, astrocytoma, myeloma, and pancreatic (column 4, lines 20-34; column 89, line 39 through column 91, line 16). Thus, the limitations of the claims are met.
Evidentiary References
Schramme et al (Cancer Immunol. Res., 2020, Vol. 8, pages 32-45) is made of record as an evidentiary reference for the following reasons. (1) The document discloses the structure of PF06845102/EOS200809 (see excerpt below) on page 35, Table 1. (2) In addition, in Table 1, it is disclosed that the enzymatic activity is evaluated in the cell line A172 human cells.
Schramme et al, page 35, Table 1
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Comments/Notes
The full scope of pending Group I was not searched because prior art was found which could be used to reject Applicant’s elected species.
Conclusion
Claims 2, 4, 7, 10, 12, 22, 24, 25, and 73 are rejected and claims 13, 14, 37, 40, 44, 45, 51, 74, 75, and 82 are withdrawn.
Future Correspondences
Any inquiry concerning this communication or earlier communications from the examiner should be directed to D L Jones whose telephone number is (571)272-0617. The examiner can normally be reached M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael G. Hartley can be reached at (571)272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/D. L. Jones/
Primary Patent Examiner
Art Unit 1618
September 4, 2026
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