DETAILED ACTION
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 of the Application
Claims 1-16 are pending in the application as of the preliminary amendment submitted 06/03/2024. Claims 1-16 are examined herein.
The compounds of Formula I as in instant claim 1 have been found to be free of prior art.
In view of the pending claims, the following objections and rejections are made, as discussed below.
Priority
This application is a 371 of PCT/US2022/027571 filed 05/04/2022, which claims priority to 63/184,460 filed 05/05/2021.
The subject matter of claims 1-16 are supported by the ‘460 provisional application and accordingly, have an effective filing date of 05/05/2021.
Information Disclosure Statement
The information disclosure statements submitted on 01/24/2024 (2), 07/15/2024, and 10/14/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in Para. [00598] and Para. [00599] of the instant specification. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 2-16 are objected to because of the following informalities:
In line 1 of claims 2-16 (all dependent claims), the reference to claim 1 or claim 15 should be written in lower case as “claim 1” or “claim 15”.
Each claim begins with a capital letter and ends with a period. See MPEP 608.01(m).
Claim Rejections - 35 USC § 112 - Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(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 15-16 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 inhibiting TREX1 comprising administering the compounds of Formula I, does not reasonably provide enablement for a method of treating all diseases responsive to TREX1 inhibition, especially cancer, because “treating” encompasses prophylactic treatment. 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 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 (Fed. Cir. 1993). The determination that "undue experimentation” would have been needed to practice the claimed invention in full scope is not a single, simple factual determination.
As stated in the MPEP 2164.01(a), “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." In re Wands, 8 USPQe2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
(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.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. Keeping that in mind, the Wands factors are relevant to the instant application for the following reasons:
The breadth of the claims/The nature of the invention
The claims recite a method of treating a disease responsive to the inhibition of TREX1 in a subject, comprising administering to the subject, a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the disease is cancer (instant claim 16). The instant specification defines “treatment” to encompass prophylactic treatment, wherein the treatment is administered to a susceptible individual prior to the onset of symptoms (Para. [0027] of the instant specification). Therefore, the scope of the method claims is extensive, as they encompass not only alleviating but also preventing each and every type of disease responsive to the inhibition of TREX1, including cancer.
The state of the prior art/The level of predictability in the art
Simpson et al. (TREX1 – Apex predator of cytosolic DNA metabolism, 12 June 2020, hereinafter Simpson); Lovly et al. (Tumor Heterogeneity and Therapeutic Resistance, 2016, hereinafter Lovly); Serrano et al. (Therapeutic cancer prevention: achievements and ongoing challenges – a focus on breast and colorectal cancer, 21 February 2019, hereinafter Serrano).
Simpson teaches heterogeneity with regard to TREX1-linked human diseases to be driven by how specific mutations influence enzyme activity, localization and immune activation (Pg. 3, second column, first full paragraph; Fig. 3). Simpson teaches TREX1 to be crucial for clearing cytosolic DNA to prevent aberrant inflammation and autoimmunity (Abstract; Pg. 5, first column, first full paragraph). Simpson teaches potential complications of TREX1 inhibition to involve unnecessary activation of the cGAS-STING pathway (Pg. 6, first column, first full paragraph). Simpson concludes that a better understanding of the precise molecular targets of TREX1 degradation is needed to devise targeted therapies (Pg. 6, first column, first full paragraph).
Lovly teaches tumor heterogeneity encompasses more than just the clinical picture and can represent both intratumor and intertumor differences (Abstract). Lovly teaches tumor heterogeneity is not one distinct term but rather encompasses several facets – within a disease, within a patient and within a tumor itself - that render tumors unique (Pg. e585, first column, last paragraph; Pg. e591, second column, first full paragraph). Lovly teaches ongoing challenges include the accurate and timely assessment of genetic changes as well as the development of resistance and the resultant compensatory mechanisms (Abstract; Pg. e586, second column, second full paragraph). Lovly, highlights the complexity of tumor heterogeneity in clinical decision making (e589-e590, case studies) and emphasizes that the need to understand the underlying causes of this heterogeneity and development of resistance, to effect better treatment outcomes (Pg. e591, second column, first full paragraph; Pg. e590, first column, first paragraph).
Serrano teaches the lack of an objective marker to target with preventive cancer therapies makes it more difficult for physicians to advise, and for candidates to undergo, treatment without a measurable outcome, particularly as they may not themselves experience a benefit but could suffer side effects (Pg. 587, first column, first full paragraph). Serrano teaches effects on cancer occurrence, as the definite endpoint, can take decades to evaluate (Pg. 580, second column, continued paragraph).
Therefore, the state of the prior art indicates heterogeneity with respect to TREX1-linked diseases, potential complications with respect to TREX1 inhibition and the need for a better understanding of the precise molecular targets of TREX1 degradation. Moreover, it is clear that there is significant variability found within and between tumors that is a major contributor to treatment failure and cancer recurrence in patients. It is also clear that cancer prevention is not well-established or predictable in consideration of the art.
Additionally, it is noted that the state of the art with regard to pharmacology is unpredictable. The field of pharmacology involves screening compounds both in vitro and in vivo to determine lead compounds that exhibit the desired pharmacological activity. According to MPEP 2164.03, “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 in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).”, with physiological activity being considered to be an unpredictable factor.
Therefore, in consideration of the high level of unpredictability in the field of cancer treatment/prevention and TREX1 inhibition, it is unclear how the claimed method would achieve the intended result of treating all conditions responsive to the inhibition of TREX1 comprising administering the compounds of the instant invention that includes prophylaxis.
The level of one of ordinary skill in the art
The relative level of skill in the art is high, such as, a synthetic organic chemist, healthcare professionals such as, an oncologist or molecular biologist with advanced educational degrees (e.g., M.D. and/or Ph.D.). Additionally there is significant unpredictability in the art regarding the development of therapies, due to the heterogenous nature of cancers.
The amount of direction provided by the inventor/The existence of working examples
Applicants have provided biochemical assays supporting the inhibition of TREX1, TREX2 and regulation of interferon signaling pathway in HCT116 (colorectal cancer cell lines) with the TREX1 inhibitor compounds (Paras. [00587]-[00589] of the instant specification). However, the disclosure does not indicate how the disclosed data correlates with the treatment of all diseases responsive to the inhibition of TREX1, specifically, treatment and prevention of all cancers. There is lack of direction or guidance regarding treatment of all types of diseases that would respond to the inhibition of TREX1.
The quantity of experimentation needed
Considering the state of the art as discussed in the references above, high degree of unpredictability in the field, and lack of sufficient guidance in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in scope with the claims.
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.
Claims 10-11 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.
Regarding claim 10, the claim depends from claim 1 and recites “wherein R5 is a halo, cyano, or -C(O)NRaRb”. Claim 1 does not recite -C(O)NRaRb as an option for R5. There is insufficient antecedent basis for this limitation in the claim.
For the purpose of applying prior art, claim 10 has been interpreted to read “wherein R5 is a halo, cyano, or -C(O)NRcRd” to provide sufficient antecedent basis.
Regarding claim 11, the claim depends from claim 1 and recites “wherein R6 is a halo, cyano, or -C(O)NRaRb”. Claim 1 does not recite -C(O)NRaRb as an option for R6. There is insufficient antecedent basis for this limitation in the claim.
For the purpose of applying prior art, claim 11 has been interpreted to read “wherein R6 is a halo, cyano, or -C(O)NRcRd” to provide sufficient antecedent basis.
Claim Rejections - 35 USC § 103
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 1-2, 4, 6, 8-12 and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Levell et al. (WO 2021/222761 A1, filing date of 30 April 2021, hereinafter Levell, in the IDS) (Levell qualifies as 35 U.S.C. 102(a)(2) prior art with a common Applicant and partial joint inventors that lists additional inventors) in view of Ali et al. (Input of Isosteric and Bioisosteric Approach in Drug Design, 2014, hereinafter Ali).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See MPEP § 717.02.
Claim Interpretation: Instant claim 1 is drawn to limitations R5 and R6, which may be absent in the compound of Formula I when q and t are 0. Therefore, R5 and R6 are considered optional. The dependent claims do not actually require the R5 and R6 substituent to be present, they simply define the species of R5 and R6 that must be present if the substituent is present in the compound. As such, a compound lacking the corresponding optional substituents still falls within the scope of the dependent claims.
Regarding instant claim 1, Levell teaches compounds of Formula (I): and pharmaceutically acceptable salts and compositions thereof, which are useful for treating a variety of conditions associated with TREX1 (Abstract; Paras. [0008]-[0009]; Claim 1).
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Levell teaches the following exemplary compound, compound 36 (Pg. 26, Table 2) having TREX1 inhibitory activity IC50 of B (1 to 10 µM) (Para. [0050]; Para. [0079]; Pg, 30, Table 3).
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Compound 36 of Levell overlaps the scope of Formula I as in instant claim 1 wherein,
R1 is C1 alkyl (methyl);
R2 is C1 alkyl (methyl);
R4 is C1 alkyl (methyl);
t is 0;
q is 0.
Compound 36 of Levell differs from the instant compounds in the presence of a “N” instead of a “CH” as instantly claimed (highlighted above).
Ali teaches isosterism or bioisosterism is one of the approaches most frequently used in the design of new molecules (Pg. 150, first column, first paragraph). Ali teaches bioisosteres may be identified as any two compounds or structures that
show similar biological activities and share analogous topology, volume, electronic arrangements or physicochemical properties (Pg. 150, first column, first paragraph). Ali teaches the isosteric replacement approach is a practical and, possibly, better
substitute to the recent lead optimization techniques to improve its pharmacokinetic i.e. absorption, distribution, metabolism and excretion (ADME) or pharmacodynamic i.e. receptor, enzyme or channel level behavior (Pg. 150, first column, first paragraph). Ali teaches N, CH to be a common trivalent bioisosteric replacement (Pg. 163, first column, last paragraph; Pg. 155, Fig. 3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Levell and Ali, to replace the highlighted “N” in compound 36 of Levell with “CH” as taught by Ali, to arrive at a compound of the instant invention, with a reasonable expectation of success. Levell teaches isoxazolyl 1,6-dihydropyrimidinecarboxamide compounds having TREX1 inhibitory activity. Levell teaches a closely-structurally related compound to the instant invention. Ali teaches N, CH to represent a group of common trivalent isosteres. Ali teaches isosterism to be an important research tool in the design of new molecules, the reason being that isosteres show similar biological activities and share analogous topology, volume, electronic arrangements or physicochemical properties.
According to MPEP 2144.09 (III), “Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979). See also In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (claimed and prior art compounds used in a method of treating depression would have been expected to have similar activity because the structural difference between the compounds involved a known bioisosteric replacement)”.
Further according to MPEP 2144.09 (I), “A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).”
In the instant case, the compounds of the instant invention are taught to be inhibitors TREX1 (Para. [0040]; Para. [00586]). The compounds of Levell are taught to show TREX1 inhibitory activity (Para. [0050]; Para. [0079]. Here, the cited compound of Levell is so close in structure that, correspondingly, the instant compounds would be expected to have very similar or identical utilities and functional properties, rendering it prima facie obvious.
Therefore, one of ordinary skill in the art would have been motivated to replace the “N” of compound 36 of Levell with CH as taught by Ali, to arrive at the instantly claimed compound of Formula I, with a reasonable expectation of success that it would act as an inhibitor of TREX1. The motivation being to improve its pharmacokinetic i.e. absorption, distribution, metabolism and excretion (ADME) or pharmacodynamic i.e. receptor, enzyme or channel level behavior (Ali, Pg. 150, first column, first paragraph).
Compound 36 of Levell further reads on the limitations of claims 2, 4, 6, and 8-12, rendering them prima facie obvious.
Regarding instant claim 14, the combined teachings of Levell and Patani render the compound of instant claim 1, prima facie obvious. Levell teaches a pharmaceutical composition comprising the compound, or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier (Para. [0051]; [0055]; Claim 21). Thus, the teachings of Levell render the limitations drawn to a pharmaceutical composition prima facie obvious.
Regarding instant claims 15-16, the combined teachings of Levell and Patani render the compound of instant claim 1, prima facie obvious. Levell teaches a method of treating a disease responsive to the inhibition of TREX1 in a subject, comprising administering to the subject, a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein the disease is cancer (Claim 22; Claim 23). Thus, the teachings of Levell render the limitations drawn to a method of treatment prima facie obvious.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-4, 6 and 8-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8, 11-12, 14-15, 25, 28 and 30-32 of co-pending Application No 18/288,455 in view of Ali et al. (Input of Isosteric and Bioisosteric Approach in Drug Design, 2014, hereinafter Ali).
Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims are drawn to compounds having similar core structures.
The instant claims are drawn to compounds of general Formula I or a pharmaceutically acceptable salt thereof, with variables as defined in instant claim 1, a pharmaceutical composition and a method of treatment thereof.
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The claims of the reference ‘455 application are drawn to compounds of general Formula I or a pharmaceutically acceptable salt thereof, with variables as defined in claim 1 of the reference application, a pharmaceutical composition and a method of treatment thereof.
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The reference ‘455 application teaches the following species of compound in claim 28 (Pg. 34 of the claim set dated 05/20/2024), 2-((1S,2R)-1-(2-cyanopyridin-3-yl)-1-phenylpropan-2-yl)-5-hydroxy-N-(isoxazol-4-yl)-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide, represented by the following structure.
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The above compound substantially overlaps the scope of a compound recited in instant claim 13.
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The compound of claim 28 of the reference ‘455 application differs from the instant compound of claim 13 with respect to the pyridinyl versus phenyl ring.
Ali teaches isosterism or bioisosterism is one of the approaches most frequently used in the design of new molecules (Pg. 150, first column, first paragraph). Ali teaches bioisosteres may be identified as any two compounds or structures that
show similar biological activities and share analogous topology, volume, electronic arrangements or physicochemical properties (Pg. 150, first column, first paragraph). Ali teaches the isosteric replacement approach is a practical and, possibly, better
substitute to the recent lead optimization techniques to improve its pharmacokinetic i.e. absorption, distribution, metabolism and excretion (ADME) or pharmacodynamic i.e. receptor, enzyme or channel level behavior (Pg. 150, first column, first paragraph). Ali teaches the benzene and pyridine rings are isosteres of each other (Pg. 153, Fig. 1; Pg. 158, Table 7).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of the reference ‘455 application and Ali, to replace the pyridinyl ring of the reference application with the phenyl ring as taught by Ali, to arrive at the instantly claimed compounds with a reasonable expectation of success. Looking into the specification of the reference ‘455 application for utility of the compounds, the compounds are taught to exhibit TREX1 inhibitory activity (specification Para. [0050] of the co-pending application). The instant compounds are taught to exhibit TREX1 inhibitory activity (Para. [0040] of the instant specification). The reference application teaches an exemplary compound that substantially overlaps the scope of the instantly claimed compound. Ali teaches the benzene and pyridine rings as biososteric ring equivalents. Ali teaches isosterism to be an important research tool in the design of new molecules, the reason being that isosteres show similar biological activities and share analogous topology, volume, electronic arrangements or physicochemical properties
According to MPEP 2144.09 (III), “Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979). See also In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (claimed and prior art compounds used in a method of treating depression would have been expected to have similar activity because the structural difference between the compounds involved a known bioisosteric replacement)”.
Further according to MPEP 2144.09 (I), “A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).”
Therefore, one of ordinary skill in the art would have been motivated to replace pyridinyl ring of the reference ‘455 application with a phenyl ring as taught by Ali, to arrive at the instantly claimed compounds, with a reasonable expectation of success that they would act as inhibitors of TREX1. The motivation being to improve its pharmacokinetic i.e. absorption, distribution, metabolism and excretion (ADME) or pharmacodynamic i.e. receptor, enzyme or channel level behavior (Ali, Pg. 150, first column, first paragraph).
Therefore, claims 1-5, 8, 11-12, 14-15, 25, 28 of the reference ‘455 application in view of Ali renders the instant compounds of claims 1-4, 6, 8-9 and 13 prima facie obvious. Claims 30-32 of the reference ‘455 application renders the instant pharmaceutical composition and method of treatment claims 14-16 prima facie obvious.
The instant claims 1-4, 6, 8-9 and 13-16 and claims 1-5, 8, 11-12, 14-15, 25, 28 and 30-32 of co-pending Application No 18/288,455 are therefore not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-4, 6 and 8-16 are rejected.
Claims 2-16 are objected to.
No claims are allowed.
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/PADMAJA S RAO/Examiner, Art Unit 1627