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
Applicant’s election without traverse of Group I, corresponding to claims 1-8, 21, 29-31, 40, 42, 43, 46, 48, 5 and 57 in the reply filed on October 23, 2025 is acknowledged.
Applicant’s election without traverse of species: 1) 5-fluorouracil (5-FU) as the specific inhibitor of thymidylate biosynthesis; 2) gastrointestinal cancer as the specific cancer; 3) anti-PD-1 antibody as the specific immunotherapy agent, in the reply filed on October 23, 2025 is acknowledged.
Claims 2, 4, 9-11, 13-20, 22-28, 32-41, 44, 45, 47, 49-54 and 56 have been canceled.
Claims 58-60 have been added.
Claims 1, 3, 6, 8, 42, 43, 46, 48, and 55 have been amended.
Claims 1, 3, 5-8, 12, 21, 29-31, 42, 43, 46, 48, 55 and 57-60 are pending.
Claims 12 and 30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions or species, there being no allowable generic or linking claim.
Claims 1, 3, 5-8, 21, 29, 31, 42, 43, 46, 48, 55 and 57-60 are pending and under consideration.
Priority
It is acknowledged that this application is a 371 of international application: PCT/US2021/039248 filed June 25, 2021, which claims the benefit of priority to U.S. Provisional Patent Appl. No. 63/044,926 filed June 26, 2020. The priority date has been established as: June 26, 2020.
Information Disclosure Statement
The Information Disclosure Statements filed on 12/15/2022, 06/08/2023, 03/01/2024 and 10/23/2025 have been considered and entered by examiner.
Improper Markush Grouping Rejection
Claims 1, 3, and 8 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
In the instant case, the Markush grouping of compounds of Formula (I), recited by claims 1, 3, and 8, is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: It cannot be said that all member of the Markush group have a single structure similarity from which the activity flows. Specifically, the species of the Markush group do not share a “single structural similarity” because there are no required structural features with each variable definition such that each member of the group would have at least one structural feature, which feature is essential to the activity/function of the claimed compounds, in common.
In addition, each alternatively usable member of the Markush group does not share a common use. Rather, the specification discloses that the compounds are useful as deoxyuridne triphosphatase (dUTPase) inhibitors; however, there is no common core in the compounds of Formula (I) that are known as dUTPase inhibitors. It is suggested that applicant amend the claims to contain only proper Markush groupings to compounds sharing a single structural similarity and a common use, wherein the common use shared by the compounds is a results of the structural similarity essential to the function of the compounds.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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.
Claim 1, 3, 5-8, 21, 29, 31, 43, 46, 48, 55 and 57-60 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 1, 3, and 8 recite that variable A can be ring
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, however, all valence positions are filled and there is no open location for the L1-L2-L3-B moiety to attach to the ring. Examiner cannot ascertain the metes and bounds of the claimed scope. Appropriate correction is required.
Regarding claims 58-60, the phrase "(such as cisplatin)" renders the claim indefinite because it is unclear whether the limitations following such as and in the parenthesis are part of the claimed invention. It is unclear whether oxaliplatin is limited to cisplatin or not.
Claims 5-7, 21, 29, 31, 43, 46, 48, 55 and 57 are also rejected because these claims depend on claim 1, 3 or 8 directly or indirectly.
Claim Rejections - 35 USC § 112
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, 3, 5-8, 21, 29, 31, 42, 43, 46, 48, 55 and 57-60 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. This is a Written Description rejection.
The claims are drawn to a method of enhancing a therapeutic efficacy of an immunotherapy (claim 1), or treating a cancer in a subject (claim 3), or inhibiting growth of a cancer cell (claim 8) with a combination of dUTPase inhibitor of formula (I), an inhibitor of thymidylate biosynthesis, and an immunotherapy agent. First the definition of Formula (I) in the independent claims 1, 3 or 8 covers a wide range of compounds share no single structural similarity and there is no common core in the compounds of Formula (I). Furthermore, these claims do not limit an inhibitor of thymidylate biosynthesis and an immunotherapy agent, but solely refer to functions of the desired compounds without providing structural features of the compounds. For example, based on paragraph [0142] of the instant publication US 2023/0263773 A1: “An “immunotherapy agent” means a type of cancer treatment which uses a patient's own immune system to fight cancer, including but not limited to a physical intervene, a chemical substance, a biological molecule or particle, a cell, a tissue or organ, or any combinations thereof, enhancing or activating or initiating a patient's immune response against cancer. Non-limiting examples of immunotherapy agents include antibodies, immune regulators, checkpoint inhibitors, an antisense oligonucleotide (ASO), a RNA interference (RNAi), a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) system, a viral vector, an anti-cancer cell therapy (e.g., transplanting an anti-cancer immune cell optionally amplified and/or activated in vivo, or administering an immune cell expressing a chimeric antigen receptor (CAR)), a CAR therapy, and cancer vaccines”. Given Broadest Reasonable Interpretation (BRI), an immunotherapy agent can be small molecule drug, peptide, protein, antibody, oligonucleotide, or siRNA, etc… These compounds vary significantly, have different structures and physical/chemical properties, and function through different mechanisms. In addition, the immunotherapy agent can function through different targets, as evidenced by the instant claim 31. Thus, the present application encompass an enormous number of combinations for the claimed methods. The instant specification provided evidence of the therapeutic activity of only one triple combination in only one cancer model (murine MC-38 model).
The results for example 1 in para. [0588]-[0590] of the instant publication report that Compound A (the elected species) + 5-FU + anti-PD-1 led to significant improvement in the antitumor efficacy when compared to all other treatment groups including all other 5-FU and anti-PD-1 combinations (Figure 1 ). The combination of Compound A + 5-FU + Anti-PD-1 was the only treatment group that led to complete inhibition of tumor growth from day 1 to day 19.
The results for Example 2 are given in par. [0610]-[0614] of the instant publication. In par. [0613], it is concluded that "these data unexpectedly demonstrate that a dUTPase inhibitor (e.g., Compound A) leads to a significant enhancement of the infiltration of both cytotoxic and regulatory T cells (measured by CDS+ CD4+ and CD3+), leukocytes (measured by CD45+) in tumor tissue when combined with an inhibitor of thymidylate biosynthesis (e.g., 5-FU) + an immunotherapy agent (e.g., an Anti-PD-1 antibody)".
Examples 3-6 (par. [0615]-[0637] of the instant publication) relate to the combination of Compound A and FUdR, which is not a triple component combination as instantly claimed.
Taken together, the instant specification provided evidence of the enhanced therapeutic activity for only one triple combination: one compound of formula (I) (compound A) with one anti-PD1 antibody (CD279) and an inhibitor of thymidylate biosynthesis (5-FU) in only one tumor model: Murine MC-38 model.
Thus, the specification does not provide sufficient written description support for the broadly claimed combinations.
Vas-Gath, Inc. v" Mahurkar, 19 USPQ2d 1111, makes clear that "to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed".
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of afunctional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., binding to antigen, high affinity, neutralization activity, competing with a reference antibody for binding), “[claiming antibodies with specific properties, e.g., an antibody that binds to human TNF-a with A2 specificity, can result in a claim that does not meet written description even if the human TNF-a protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
In addition, the instant claims define the compositions in the combination by function only, where the function is to:
enhancing a therapeutic efficacy of an immunotherapy
treating cancers
inhibiting growth of cancer cells
reducing tumor size
increasing overall survival
inhibiting metastasis
minimizing toxicity and/or
avoiding side-effects
However, the instant specification has not provided a sufficient description about the correlation between the recited functions and the claimed combination. For example, antibodies to PD-1 do not teach the structure of other types of anti-PD-1 agent, or other agents targeting to different genes, or different types of immunotherapy agents (such as small molecule drug, peptide, protein, oligonucleotide, RNAi or CRISPR system, etc…) which could be used in the combination and could produce the desired activities. Thus, one of ordinary skill in the art would not be able to readily visualize or recognize other combinations (other than the one described in Example 1) would lead to the same outcome as showed in the Example 1 of the instant specification.
Also, it is noted that the Court has held that the disclosure of screening assays and general classes of compounds was not adequate to describe compounds having the desired activity: without disclosure of which peptides, polynucleotides, or small organic molecules have the desired characteristic, the claims failed to meet the description requirement of§ 112. See University of Rochester v. G.D. Searle & Co., Inc., 69 USPQ2d 1886,1895 (Fed. Cir. 2004). Meeting the written description threshold requires showing that the applicant was in "possession" of the claimed invention at the time of filing. Vas-Cath, 935 F.2d at 1563-1564. Support need not describe the claimed subject matter in exactly the same terms as used in the claims. Eiselstein v. Frank, 52 F.3d 1035, 1038 (Fed. Cir. 1995). This support cannot be based on obviousness reasoning - i.e., what the written description and knowledge in the art would lead one to speculate as to modifications the inventor might have envisioned, but failed to disclose. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997). Ariad points out, the written description requirement also ensures that when a patent claims a genus by function, the specification recites sufficient materials to accomplish that function - a problem that is particularly acute in biological arts." Ariad, 598 F.3d at 1352-3. Note the following Court Decisions regarding the written description of antibodies in the context of the current claims. Given the claimed broadly class of antibody binding domains, in the absence of sufficient disclosure of relevant identifying characteristics, the patentee must establish "a reasonable structure-function correlation" either within the specification or by reference to the knowledge of one skilled in the art with functional claims. AbbVie Deutsch/and GmbH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014) and the specification at best describes plan for making antibodies with the "limitations above" and then identifying those that satisfy claim limitations, but mere "wish or plan" for obtaining claimed invention is not sufficient. Centocor Ortho Biotech Inc. v. Abbott Laboratories, 97 USPQ2d 1870 (Fed. Cir. 2011). There is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed antibody binding domains to demonstrate possession. Also, see Amgen Inc. v. Sanofi, Aventisub LLC, No. 2017-1480 (Fed. Cir. 2017).
Taken together, the instant specification lacks written description for the broadly claimed inventions.
Claim Rejections - 35 USC § 112
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, 3, 5-8, 21, 29, 31, 42, 43, 46, 48, 55 and 57-60 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:
“A method of enhancing a therapeutic efficacy of an immunotherapy agent in a subject in need thereof, comprising administering to the subject an effective amount of a deoxyuridine triphosphatase (dUTPase) inhibitor, an effective amount of an inhibitor of thymidylate biosynthesis, and the immunotherapy agent; wherein the dUTPase inhibitor is compound A or a pharmaceutically acceptable salt thereof, wherein the inhibitor of wherein the inhibitor of thymidylate biosynthesis comprises 5-fluorouracil (5-FU), floxuridine (FUdR), pemetrexed, raltitrexed, nolatrexed, plevitrexed, GS7904L, capecitabine, methotrexate, pralatrexate, CT-900, NUC-3373, or a combination of two or more thereof; or S-1, a combination of S-1 and folinic acid, FOLFOX, FOLFOX-4, FOLFIRI, MOF, deflexifol, or a combination of 5-FU with one or more selected from radiation, methyl-CCNU, leucovorin, arfolitixorin, oxaliplatin, cisplatin, irinotecan, mitomycin, cytarabine, and levamisole; and wherein the immunotherapy agent is an anti-PD1 antibody”, does not reasonably provide enablement for the method as recited by claim 1.
“A method of inhibiting or ameliorating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of a deoxyuridine triphosphatase (dUTPase) inhibitor, an effective amount of an inhibitor of thymidylate biosynthesis, and the immunotherapy agent; wherein the dUTPase inhibitor is compound A or a pharmaceutically acceptable salt thereof, wherein the inhibitor of wherein the inhibitor of thymidylate biosynthesis comprises 5-fluorouracil (5-FU), floxuridine (FUdR), pemetrexed, raltitrexed, nolatrexed, plevitrexed, GS7904L, capecitabine, methotrexate, pralatrexate, CT-900, NUC-3373, or a combination of two or more thereof; or S-1, a combination of S-1 and folinic acid, FOLFOX, FOLFOX-4, FOLFIRI, MOF, deflexifol, or a combination of 5-FU with one or more selected from radiation, methyl-CCNU, leucovorin, arfolitixorin, oxaliplatin, cisplatin, irinotecan, mitomycin, cytarabine, and levamisole; and wherein the immunotherapy agent is an anti-PD1 antibody”, does not reasonably provide enablement for the method as recited by claim 3.
“A method of inhibiting growth of a cancer cell comprising contacting the cell with an effective amount of a deoxyuridine triphosphatase (dUTPase) inhibitor, an effective amount of an inhibitor of thymidylate biosynthesis, and the immunotherapy agent; wherein the dUTPase inhibitor is compound A or a pharmaceutically acceptable salt thereof, wherein the inhibitor of thymidylate biosynthesis comprises 5-fluorouracil (5-FU), floxuridine (FUdR), pemetrexed, raltitrexed, nolatrexed, plevitrexed, GS7904L, capecitabine, methotrexate, pralatrexate, CT-900, NUC-3373, or a combination of two or more thereof; or S-1, a combination of S-1 and folinic acid, FOLFOX, FOLFOX-4, FOLFIRI, MOF, deflexifol, or a combination of 5-FU with one or more selected from radiation, methyl-CCNU, leucovorin, arfolitixorin, oxaliplatin, cisplatin, irinotecan, mitomycin, cytarabine, and levamisole; and wherein the immunotherapy agent is an anti-PD1 antibody”, does not reasonably provide enablement for the method of as recited by claim 8.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or 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). 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).
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by 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 to consider when assessing whether or not a disclosure would require undue experimentation. These factors are:
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 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:
The scope of the claims are very broad. First the definition of Formula (I) in the independent claims 1, 3 or 8 covers a wide range of compounds share no single structural similarity and there is no common core in the compounds of Formula (I). Furthermore, these claims do not limit an inhibitor of thymidylate biosynthesis and an immunotherapy agent, but solely refer to functions of the desired compounds without providing structural features of the compounds. For example, based on paragraph [0142] of the instant publication US 2023/0263773 A1: “An “immunotherapy agent” means a type of cancer treatment which uses a patient's own immune system to fight cancer, including but not limited to a physical intervene, a chemical substance, a biological molecule or particle, a cell, a tissue or organ, or any combinations thereof, enhancing or activating or initiating a patient's immune response against cancer. Non-limiting examples of immunotherapy agents include antibodies, immune regulators, checkpoint inhibitors, an antisense oligonucleotide (ASO), a RNA interference (RNAi), a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) system, a viral vector, an anti-cancer cell therapy (e.g., transplanting an anti-cancer immune cell optionally amplified and/or activated in vivo, or administering an immune cell expressing a chimeric antigen receptor (CAR)), a CAR therapy, and cancer vaccines”. Given Broadest Reasonable Interpretation (BRI), an immunotherapy agent can be small molecule drug, peptide, protein, antibody, oligonucleotide, or siRNA, etc… These compounds vary significantly, have different structures and physical/chemical properties, and function through different mechanisms. In addition, the immunotherapy agent can function through different targets, as evidenced by the instant claim 31. Thus, the present application encompass an enormous number of combinations for the claimed methods. The instant specification provided evidence of the therapeutic activity of only one triple combination in only one cancer model (murine MC-38 model).
As instantly claimed, the components in the combination vary significantly and function through different mechanism and/or through different targets. In addition, the claims also encompass various cancers. The effects of different combinations on different cancers can’t be predicted, and can be determined only through in vitro and/or in vivo tests.
In the instant case, the results for Example 1 in para. [0588]-[0590] of the instant publication report that Compound A (the elected species) + 5-FU + anti-PD-1 led to significant improvement in the antitumor efficacy when compared to all other treatment groups including all other 5-FU and anti-PD-1 combinations (Figure 1 ). The combination of Compound A + 5-FU + Anti-PD-1 was the only treatment group that led to complete inhibition of tumor growth from day 1 to day 19.
The results for Example 2 are given in par. [0610]-[0614] of the instant publication. In par. [0613], it is concluded that "these data unexpectedly demonstrate that a dUTPase inhibitor (e.g., Compound A) leads to a significant enhancement of the infiltration of both cytotoxic and regulatory T cells (measured by CDS+ CD4+ and CD3+), leukocytes (measured by CD45+) in tumor tissue when combined with an inhibitor of thymidylate biosynthesis (e.g., 5-FU) + an immunotherapy agent (e.g., an Anti-PD-1 antibody)".
Examples 3-6 (par. [0615]-[0637] of the instant publication) relate to the combination of Compound A and FUdR, which is not a triple component combination as instantly claimed.
Taken together, the instant specification provided evidence of the enhanced therapeutic activity for only one triple combination: one compound of formula (I) (compound A) with one anti-PD1 antibody (CD279) and an inhibitor of thymidylate biosynthesis (5-FU) in only one tumor model: Murine MC-38 model.
It is also noted that based on paragraph [0134] of the instant publication US 2023/0263773 A1, “treating” would encompass preventing the symptoms or disease from occurring in a subject that is not yet display symptoms of the disease. Thus, instant claim 3 would even encompass preventing cancers. No working examples has been provided for preventing any disease.
The factors outlined in In Re Wands' mentioned above apply here, and in particular as per the MPEP 2164.01 (a): "A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)." It is very clear that one could not make/use this very broad invention that has no working examples in this unpredictable art without undue experimentation. Genetech Inc vs Nova Nordisk 42 USPQ 2d 1001 "A patent is not a hunting license. It is not a reward for search but 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.”
Given the numerous combinations and cancers encompassed by these claims, the lack of specific guidance and the insufficient working examples, undue experimentation would be required of one of skilled in the art to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Claim Rejections - 35 USC § 103
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 1, 3, 5-8, 21, 29, 31, 42, 43, 46, 48, 55 and 57-60 are rejected under 35 U.S.C. 103 as being unpatentable over Suzuki (Suzuki, EP3400963A1, Publication Date: 11/14/2018, cited in IDS of 12/15/2022) in view of Spyvee (Spyvee et al., WO 2017/006282 A1, Publication Date: 01/12/2017, cited in IDS of 12/15/2022).
Suzuki teaches a drug comprising a drug containing a DNA function inhibitor (such as dUTPase inhibitor and a fluorinated pyrimidine antimetabolite) and an immunomodulator (such as an anti-PD-1 antibody) ([0013], claims 1, 2 and 6).
Suzuki teaches that the fluorinated pyrimidine antimetabolite can be a combination drug containing tegafur, gimeracil, and oteracil potassium in a molar ratio of 1 : 0.4 : 1, or capecitabine (claim 5). As evidenced by [0023] of Suzuki, the combination of tegafur, gimeracil, and oteracil potassium is also called S-1. As evidenced by instant claims 58-60, S-1 and capecitabine are inhibitors of thymidylate biosynthesis. Suzuki also teaches other fluorinated pyrimidine antimetabolite and anti-tumor drug, such as 5-fluorouracil (5-FU) ([0004], [0009], [0023]). It is known in the art that a fluorinated pyrimidine antimetabolite acts as a thymidylate biosynthesis inhibitor, as evidenced by the instant claims 58-60.
Suzuki teaches a method of treating tumor by administering effective dose of a DNA function inhibitor (such as dUTPase inhibitor and a fluorinated pyrimidine antimetabolite) and an immunomodulator (such as an anti-PD-1 antibody) (claims 62, 63, 67, 68).
Suzuki teaches a specific dUTPase inhibitor: Compound I ([0021]).
Example 4 of Suzuki teaches that combination of S-1+Compound 1+anti-PD-1 antibody (the elected species) shows enhanced anti-tumor activity (Table 10), in a colorectal carcinoma model (CMT-93 tumor model). It is noted that colorectal cancer is a type of gastrointestinal cancer (the elected species).
Suzuki teaches that the three drug combination was found to have a statistically significant effect of combination use of any other two drug combination ([0113], Example 4, Fig. 16, Table 10).
Suzuki teaches the invention is not limited to each of embodiments and examples described above, and various modifications can be employed ([0115]).
Taken together, Suzuki teaches a method of treating cancer, enhancing an immunotherapy efficacy, or inhibiting cancer cell growth in a subject by administering a combination of a deoxyuridine triphosphatase (dUTPase) inhibitor (such as Compound 1), an inhibitor of thymidylate biosynthesis (a fluorinated pyrimidine antimetabolite, such as S-1) and an anti-PD-1 antibody (the elected species).
However, Suzuki does not teach a dUTPase inhibitor with a structure of instantly claimed, such as Compound A of the instant application (the elected species).
Spyvee teaches various dUTPase inhibitors of Formula I (claim 1).
Spyvee teaches the dUTPase inhibitor with the structure shown below (see Production Example Number 1 in Table 1 on page 83):
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This compound is identical to the first compound listed in the instant claim 57 (the elected species). This compound is the same as Compound A used in the Examples (see paragraph [0590] of the instant publication US 2023/0263773 A1).
Compound A is a compound of Formula (I):
wherein A is:
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wherein L1 is:
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wherein L2 is: -SO2NR50-, wherein R50 is a hydrogen;
wherein L3 is:
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wherein B is:
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Thus, the compound taught by Spyvee reads on the dUTPase inhibitor of all pending claims, such as claims 1, 3, 8, 42, 43, 46, 48, 55, 57.
Spyvee teaches method of production of the compound (§ Synthesis Examples, [0452]-[0453]).
Spyvee teaches a method of treating and inhibiting cancer using dUTPase inhibitors (claims 23-30).
Spyvee teaches that the dUTPase inhibitor can be used in combination with an agent which is suitable for treating the disease ([0173]), such as 5-FU, capecitabine, S-1 ([0301] and [0302]).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to modified the methods taught by Suzuki by substituting the dUTPase inhibitor (compound 1) in the three-drug combination (e.g. compound 1 + S-1 + anti-PD1 antibody) with a dUTPase inhibitor (such as Compound A) taught by Spyvee. One of ordinary skill in the art would have had a reasonable expectation that the combination of Compound A + S-1 + anti-PD1 antibody would be able to treat and inhibit cancer and to enhance the therapeutic efficacy because compound A and compound 1 have similar activity: inhibiting dUTPase and can be used in treating cancers, as taught by Suzuki and Spyvee. One of ordinary skill in the art would have a reasonable expectation to reach the claimed invention because references teaches that the method can be modified for different embodiments; the method of producing Compound A is known; Compound A can be used in treating and inhibiting cancers (e.g. colorectal cancer); Compound A can be used in combination with an inhibitor of thymidylate biosynthesis. The motivation would have been to expand the options of the three drug combination and to develop better combinations for cancer treatment.
Regarding claim 5, Suzuki teaches that the triple combination can reduce the tumor size (Fig. 16).
Regarding claims 6 and 7, Example 4 of Suzuki teaches that the triple combination shows enhanced anti-tumor activity (Table 10), in a colorectal carcinoma model (CMT-93 tumor model). It is noted that colorectal cancer is a type of gastrointestinal cancer (the elected species).
Suzuki teaches anti-PD-1 antibody in the combination, which would read the instant claims 21, 29, 31.
Regarding claims 58-60, Suzuki teaches S-1 and 5-FU (the elected species) as exemplary fluorinated pyrimidine antimetabolite and anti-tumor drug ([0004], [0009], [0023], and Example 4).
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.
U.S. Patent No. 10,570,098
Claims 1, 3, 5-8, 21, 29, 31, 42, 43, 46, 48, 55 and 57-60 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,570,098 B2 (herein after Pat. 098, cited in IDS of 06/08/2023) in view of Suzuki (Suzuki, EP3400963A1, Publication Date: 11/14/2018, cited in IDS of 12/15/2022) and Spyvee (Spyvee et al., WO 2017/006282 A1, Publication Date: 01/12/2017, cited in IDS of 12/15/2022).
The claims of Pat. 098 teach a method of a. one or more of inhibiting dUTPase or enhancing the efficacy of a dUTPase directed therapy; or b. reversing resistance to a dUTPase-directed therapy comprising contacting the dUTPase with a therapeutically effective amount of a compound of Formula (I):… (claim 1).
The claims of Pat. 098 teach 2. a method of treating a disease in a patient whose treatment is impeded by the expression or over expression of dUTPase, comprising:
administering to the patient in need of such treatment a therapeutically effective amount of a compound of Formula (I), or …; or
screening a cell or tissue sample from the patient; determining the expression level of dUTPase in the sample; and administering to a patient whose sample shows over expression of dUTPase, a therapeutically effective amount of the compound of Formula (I), or …(claim 2);
wherein the disease is a cancer (claim 5); wherein the cancer is selected from the group consisting of colon cancer, colorectal cancer, gastric cancer… (claim 6).
The claims of Pat. 098 teach a method of inhibiting the growth of a cancer cell comprising contacting the cell with a therapeutically effective amount of the compound of Formula (I), or …; and a therapeutically effective amount of a dUTPase directed therapeutic, thereby inhibiting the growth of the cancer cell; wherein Formula (I) … (claim 3)
The claims 19 and 20 of Pat. 098 teach the method of claim 1 or the method of claim 2, wherein the compound can be:
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It is noted that the compound above is identical to the first compound listed in the instant claim 57 (the elected species). This compound is the same as Compound A used in the Examples of the instant Application (see paragraph [0590] of the instant publication US 2023/0263773 A1). Thus, the compound of Pat. 098 reads on the dUTPase inhibitor of all pending claims, such as claims 1, 3, 8, 42, 43, 46, 48, 55, 57.
Taken together, the claims of Pat. 098 teach methods of enhancing dUTPase directed therapy, or treating cancers, or inhibiting cancer cell growth with dUTPase inhibitors of Formula (I), including the elected compound of the instant application. However, the claims of Pat. 098 do not teach using the dUTPase in combination with inhibitor of thymidylate biosynthesis (such as S-1 or 5-FU) and an immunotherapy agent (such as anti-PD-1 antibody), as instantly claimed.
Suzuki and Skyvee’s teachings are described above. In particular, Suzuki teaches a combination of a dUTPase inhibitor (compound I), an inhibitor of thymidylate biosynthesis (S-1), and an anti-PD-1 antibody, shows enhanced anti-tumor activity (Table 10), in a colorectal carcinoma model (CMT-93 tumor model). Suzuki teaches that the three drug combination was found to have a statistically significant effect of combination use to any other two drug combination ([0113], Example 4, Fig. 16, Table 10). Skyvee teaches the method of making Compound A. Spyvee teaches that the dUTPase inhibitor can be used in combination with an agent which is suitable for treating the disease ([0173]), such as 5-FU, capecitabine, S-1 ([0301] and [0302]).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to use dUTPase inhibitor such as compound A to treat cancer or inhibit cancer cell growth as taught by the claims of Pat. 098 and to modify the method and to use the inhibitor in combination with an inhibitor of thymidylate biosynthesis (such as S-1, or 5-FU), and an anti-PD-1 antibody as taught by Suzuki and Skyvee. One of ordinary skill in the art would have had a reasonable expectation that the combination (such as Compound A + S-1 + anti-PD1 antibody) would be able to treat and inhibit cancer and to enhance the therapeutic efficacy because the combination of a dUTPase inhibitor, an inhibitor of thymidylate biosynthesis, and an anti-PD-1 antibody showed enhanced anti-tumor activity, Compound A is a well-known dUTPase inhibitor as taught by Suzuki and Spyvee. One of ordinary skill in the art would have a reasonable expectation to reach the claimed invention because references teaches that the method can be modified for different embodiments; the method of producing Compound A is known; Compound A can be used in treating and inhibiting cancers (e.g. colorectal cancer); Compound A can be used in combination with an inhibitor of thymidylate biosynthesis. The motivation would have been to expand the options of the three drug combination and to develop better combinations for cancer treatment.
U.S. Patent No. 10,562,860
Claims 1, 3, 5-8, 21, 29, 31, 42, 43, 46, 48, 55 and 57-60 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 10,562,860 B2 (herein after Pat. 860, cited in IDS of 06/08/2023) in view of Suzuki (Suzuki, EP3400963A1, Publication Date: 11/14/2018, cited in IDS of 12/15/2022) and Spyvee (Spyvee et al., WO 2017/006282 A1, Publication Date: 01/12/2017, cited in IDS of 12/15/2022).
The claims of Pat. 860 teach a compound of structure shown below (see claim 10):
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It is noted that the compound above is identical to the first compound listed in the instant claim 57 (the elected species). This compound is the same as Compound A used in the Examples of the instant Application (see paragraph [0590] of the instant publication US 2023/0263773 A1). As set forth above, the compound of Pat. 098 reads on the dUTPase inhibitor of all pending claims, such as claims 1, 3, 8, 42, 43, 46, 48, 55, 57.
The claims of Pat. 860 teach the compound above. However, the claims of Pat. 860 do not teach the method of enhancing dUTPase directed therapy, or treating cancers, or inhibiting cancer cell growth with dUTPase inhibitors of Formula (I), in combination with inhibitor of thymidylate biosynthesis (such as S-1 or 5-FU) and an immunotherapy agent (such as anti-PD-1 antibody), as instantly claimed.
Suzuki and Skyvee’s teachings are described above. In particular, Suzuki teaches a combination of a dUTPase inhibitor (compound I), an inhibitor of thymidylate biosynthesis (S-1), and an anti-PD-1 antibody, shows enhanced anti-tumor activity (Table 10), in a colorectal carcinoma model (CMT-93 tumor model). Suzuki teaches that the three drug combination was found to have a statistically significant effect of combination use to any other two drug combination ([0113], Example 4, Fig. 16, Table 10). Skyvee teaches the method of making Compound A. Spyvee teaches that the dUTPase inhibitor can be used in combination with an agent which is suitable for treating the disease ([0173]), such as 5-FU, capecitabine, S-1 ([0301] and [0302]).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to make the dUTPase inhibitor such as compound A as taught by the claims of Pat. 86011 and to use the inhibitor in combination with an inhibitor of thymidylate biosynthesis (such as S-1, or 5-FU), and an anti-PD-1 antibody as taught by Suzuki and Skyvee. One of ordinary skill in the art would have had a reasonable expectation that the combination (such as Compound A + S-1 + anti-PD1 antibody) would be able to treat and inhibit cancer and to enhance the therapeutic efficacy because the combination of a dUTPase inhibitor, an inhibitor of thymidylate biosynthesis, and an anti-PD-1 antibody showed enhanced anti-tumor activity, Compound A is a well-known dUTPase inhibitor as taught by Suzuki and Spyvee. One of ordinary skill in the art would have a reasonable expectation to reach the claimed invention because references teaches that the method can be modified for different embodiments; the method of producing Compound A is known; Compound A can be used in treating and inhibiting cancers (e.g. colorectal cancer); Compound A can be used in combination with an inhibitor of thymidylate biosynthesis. The motivation would have been to develop a more powerful combination therapy for cancer treatment.
U.S. Patent No. 10,858,344
Claims 1, 3, 5-8, 21, 29, 31, 42, 43, 48, 55 and 57-60 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 10,858,344 B2 (herein after Pat. 344, cited in IDS of 06/08/2023) in view of Suzuki (Suzuki, EP3400963A1, Publication Date: 11/14/2018, cited in IDS of 12/15/2022) and Spyvee (Spyvee et al., WO 2017/006282 A1, Publication Date: 01/12/2017, cited in IDS of 12/15/2022).
The claims of Pat. 344 teach a compound selected from:
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It is noted that the compound shown above are identical to three compounds listed in the instant claim 57 (see compounds of col. 1-row 2, col. 1-row 6, and col. 2-row 6, respectively).
The compounds shown above are compounds of Formula (I):
wherein A is:
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wherein L1 is:
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wherein L3 is a bond
wherein B is:
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Thus, the claims of Pat. 344 teach compounds which read on the dUTPase inhibitor of instant claims 1, 3, 8, 42, 43, 48, 55 and 57.
The claims of Pat. 344 teach a method of inhibiting the growth of a cancer cell comprising contacting the cell with a therapeutically effective amount of the compound of claim 1 and a therapeutically effective amount of a dUTPase directed therapeutic, thereby inhibiting the growth of the cancer cell (claim 4).
The claims of Pat. 344 teach the method of claim 4, wherein the cancer cell is selected from a colon cancer cell, a colorectal cancer cell, a gastric cancer cell, an esophageal cancer cell, a head and neck cancer cell, a breast cancer cell, a lung cancer cell, a stomach cancer cell, a liver cancer cell, a gall bladder cancer cell, a pancreatic cancer cell, and a leukemia cell (claim 5).
Taken together, the claims of Pat. 344 teach methods of inhibiting cancer cell growth with dUTPase inhibitors of Formula (I). However, the claims of Pat. 344 do not teach using the dUTPase in combination with inhibitor of thymidylate biosynthesis (such as S-1 or 5-FU) and an immunotherapy agent (such as anti-PD-1 antibody), as instantly claimed.
Suzuki and Skyvee’s teachings are described above. In particular, Suzuki teaches a combination of a dUTPase inhibitor (compound I), an inhibitor of thymidylate biosynthesis (S-1), and an anti-PD-1 antibody, shows enhanced anti-tumor activity (Table 10), in a colorectal carcinoma model (CMT-93 tumor model). Suzuki teaches that the three drug combination was found to have a statistically significant effect of combination use to any other two drug combination ([0113], Example 4, Fig. 16, Table 10). Skyvee teaches dUTPase inhibitors of Formula (I) and the method of making these compounds. Spyvee teaches that the dUTPase inhibitor can be used in combination with an agent which is suitable for treating the disease ([0173]), such as 5-FU, capecitabine, S-1 ([0301] and [0302]).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to use dUTPase inhibitor of Formula (I) inhibit cancer cell growth as taught by the claims of Pat. 344 and to modify the method and to use the inhibitor in combination with an inhibitor of thymidylate biosynthesis (such as S-1, or 5-FU), and an anti-PD-1 antibody as taught by Suzuki and Skyvee. One of ordinary skill in the art would have had a reasonable expectation that the combination (such as the compound of taught by the claims of Pat. 344 + S-1 + anti-PD1 antibody) would be able to treat and inhibit cancer and to enhance the therapeutic efficacy because the combination of a dUTPase inhibitor, an inhibitor of thymidylate biosynthesis, and an anti-PD-1 antibody showed enhanced anti-tumor activity, Compound of Formula (I) is a well-known dUTPase inhibitor as taught by Suzuki and Spyvee. One of ordinary skill in the art would have a reasonable expectation to reach the claimed invention because references teaches that the method can be modified for different embodiments; the method of producing the dUTPase inhibitors is known; dUTPase inhibitors can be used in treating and inhibiting cancers (e.g. colorectal cancer); dUTPase inhibitors can be used in combination with an inhibitor of thymidylate biosynthesis to enhance therapeutic efficacy. The motivation would have been to expand the options of the three drug combination and to develop better combinations for cancer treatment.
This is a provisional nonstatutory double patenting rejection.
U.S. Patent No. 11,014,924
Claims 1, 3, 5-8, 21, 29, 31, 42, 46, 48, 55 and 57-60 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,014,924 B2 (herein after Pat. 924, cited in IDS of 06/08/2023) in view of Suzuki (Suzuki, EP3400963A1, Publication Date: 11/14/2018, cited in IDS of 12/15/2022) and Spyvee (Spyvee et al., WO 2017/006282 A1, Publication Date: 01/12/2017, cited in IDS of 12/15/2022).
The claims of Pat. 924 teach a compound selected from:
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It is noted that the compound shown above are identical to four compounds listed in the instant claim 57 (see compounds of col. 2-row 5, col. 1-row 6, col.1-row 7 and col. 2-row 7, respectively).
The compounds shown above are compounds of Formula (I):
wherein A is:
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wherein L2 is: -SO2NR50-, wherein R50 is a hydrogen;
wherein L3 is:
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wherein B is:
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Thus, the claims of Pat. 924 teach compounds which read on the dUTPase inhibitor of instant claims 1, 3, 8, 42, 46, 48, 55 and 57.
The claims of Pat. 924 teach a method of inhibiting the growth of a cancer cell comprising contacting the cell with a therapeutically effective amount of the compound of claim 1 and a therapeutically effective amount of a dUTPase directed therapeutic, thereby inhibiting the growth of the cancer cell (claim 4).
The claims of Pat. 924 teach the method of claim 4, wherein the cancer cell is selected from a colon cancer cell, a colorectal cancer cell, a gastric cancer cell, an esophageal cancer cell, a head and neck cancer cell, a breast cancer cell, a lung cancer cell, a stomach cancer cell, a liver cancer cell, a gall bladder cancer cell, a pancreatic cancer cell, and a leukemia cell (claim 5).
Taken together, the claims of Pat. 924 teach methods of inhibiting cancer cell growth with dUTPase inhibitors of Formula (I). However, the claims of Pat. 924 do not teach using the dUTPase in combination with inhibitor of thymidylate biosynthesis (such as S-1 or 5-FU) and an immunotherapy agent (such as anti-PD-1 antibody), as instantly claimed.
Suzuki and Skyvee’s teachings are described above. In particular, Suzuki teaches a combination of a dUTPase inhibitor (compound I), an inhibitor of thymidylate biosynthesis (S-1), and an anti-PD-1 antibody, shows enhanced anti-tumor activity (Table 10), in a colorectal carcinoma model (CMT-93 tumor model). Suzuki teaches that the three drug combination was found to have a statistically significant effect of combination use to any other two drug combination ([0113], Example 4, Fig. 16, Table 10). Skyvee teaches dUTPase inhibitors of Formula (I) and the method of making these compounds. Spyvee teaches that the dUTPase inhibitor can be used in combination with an agent which is suitable for treating the disease ([0173]), such as 5-FU, capecitabine, S-1 ([0301] and [0302]).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to use dUTPase inhibitor of Formula (I) inhibit cancer cell growth as taught by the claims of Pat. 924 and to modify the method and to use the inhibitor in combination with an inhibitor of thymidylate biosynthesis (such as S-1, or 5-FU), and an anti-PD-1 antibody as taught by Suzuki and Skyvee. One of ordinary skill in the art would have had a reasonable expectation that the combination (such as the compound of taught by the claims of Pat. 924 + S-1 + anti-PD1 antibody) would be able to treat and inhibit cancer and to enhance the therapeutic efficacy because the combination of a dUTPase inhibitor, an inhibitor of thymidylate biosynthesis, and an anti-PD-1 antibody showed enhanced anti-tumor activity, Compound of Formula (I) is a well-known dUTPase inhibitor as taught by Suzuki and Spyvee. One of ordinary skill in the art would have a reasonable expectation to reach the claimed invention because references teaches that the method can be modified for different embodiments; the method of producing the dUTPase inhibitors is known; dUTPase inhibitors can be used in treating and inhibiting cancers (e.g. colorectal cancer); dUTPase inhibitors can be used in combination with an inhibitor of thymidylate biosynthesis to enhance therapeutic efficacy. The motivation would have been to expand the options of the three drug combination and to develop better combinations for cancer treatment.
This is a provisional nonstatutory double patenting rejection.
U.S. Patent No. 11,104,649
Claims 1, 3, 5-8, 21, 29, 31, 42, 43, 46, 48, 55 and 57-60 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,104,649 B2 (herein after Pat. 649, cited in IDS of 06/08/2023) in view of Suzuki (Suzuki, EP3400963A1, Publication Date: 11/14/2018, cited in IDS of 12/15/2022) and Spyvee (Spyvee et al., WO 2017/006282 A1, Publication Date: 01/12/2017, cited in IDS of 12/15/2022).
The claims of Pat. 649 teach a compound of formula (I):
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Based on the definition of each variable of formula (I), the compounds of Pat. 649 represent a subset of the compounds encompassed by the instant claim 1, 3, and 8. Because for each of A, L1, L2, L3 and B, the scope for the instant claim 1, 3 or 8 is broader than that of claim 1 of Pat. 649.
Claim 7 of Pat. 649 teaches that the compound of claim 1, wherein L1 can be:
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…
which read on the instant claim 43.
Claim 9 of Pat. 649 teach that the compound of claim 1, wherein L2 is -S(O)2NH- wherein the sulfur is attached to L1.
Claim 12 of Pat. 649 teach that the compound of claim 1, wherein L3 can be:
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which read on the instant claim 46.
Claim 13 of Pat. 649 teach that the compound of claim 1, wherein B is
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Based on the definition of claim 1, R20 is CH2-R21; methyl optionally substituted with 2 or 3 fluorine atoms; C3-C6 cycloalkyl; or C1-C6 alkyl; and R21 is C1-C10 alkyl optionally substituted with one or more hydroxy or fluoro; or C3-C6 cycloalkyl. Taken together, claim 13 of Pat. 649 read on the instant claim 48 and overlap with the scope of instant claims 55 and 57.
Claim 15 of Pat. 649 teaches a method of treating a disease in a patient whose treatment is impeded by the expression or over expression of dUTPase, comprising:
administering to the patient in need of such treatment a therapeutically effective amount of the compound of claim 1, wherein the disease is cancer (claim 16), wherein the cancer is selected from the group consisting of colon cancer, colorectal cancer, gastric cancer, esophageal cancer, head and neck cancer, breast cancer, lung cancer, stomach cancer, liver cancer, gall bladder cancer, pancreatic cancer and leukemia (claim 17).
Claim 18 of Pat. 649 teaches a method of inhibiting the growth of a cancer cell comprising contacting the cell with a therapeutically effective amount of the compound of claim 1; and a therapeutically effective amount of a dUTPase directed therapeutic, thereby inhibiting the growth of the cancer cell; wherein the cancer cell is selected from a colon cancer cell, a colorectal cancer cell, a gastric cancer cell, a head and neck cancer cell, a breast cancer cell, a lung cancer cell or a blood cell (claim 19).
Taken together, the claims of Pat. 649 teach methods of treating cancers, or inhibiting cancer cell growth with dUTPase inhibitors of Formula (I). However, the claims of Pat. 649 do not teach using the dUTPase in combination with inhibitor of thymidylate biosynthesis (such as S-1 or 5-FU) and an immunotherapy agent (such as anti-PD-1 antibody), as instantly claimed.
Suzuki and Skyvee’s teachings are described above. In particular, Suzuki teaches a combination of a dUTPase inhibitor (compound I), an inhibitor of thymidylate biosynthesis (S-1), and an anti-PD-1 antibody, shows enhanced anti-tumor activity (Table 10), in a colorectal carcinoma model (CMT-93 tumor model). Suzuki teaches that the three drug combination was found to have a statistically significant effect of combination use to any other two drug combination ([0113], Example 4, Fig. 16, Table 10). Skyvee teaches dUTPase inhibitors of Formula (I) (such as compound A) and the method of making these compounds. Spyvee teaches that the dUTPase inhibitor can be used in combination with an agent which is suitable for treating the disease ([0173]), such as 5-FU, capecitabine, S-1 ([0301] and [0302]).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to use dUTPase inhibitor of Formula (I) to treat cancer or inhibit cancer cell growth as taught by the claims of Pat. 649 and to modify the method and to use the inhibitor in combination with an inhibitor of thymidylate biosynthesis (such as S-1, or 5-FU), and an anti-PD-1 antibody as taught by Suzuki and Skyvee. One of ordinary skill in the art would have had a reasonable expectation that the combination (such as the compound of taught by the claims of Pat. 649 + S-1 + anti-PD1 antibody) would be able to treat and inhibit cancer and to enhance the therapeutic efficacy because the combination of a dUTPase inhibitor, an inhibitor of thymidylate biosynthesis, and an anti-PD-1 antibody showed enhanced anti-tumor activity, Compound of Formula (I) (such as compound A) is a well-known dUTPase inhibitor as taught by Suzuki and Spyvee. One of ordinary skill in the art would have a reasonable expectation to reach the claimed invention because references teaches that the method can be modified for different embodiments; the method of producing the dUTPase inhibitors (such as compound A) is known; dUTPase inhibitors can be used in treating and inhibiting cancers (e.g. colorectal cancer); dUTPase inhibitors can be used in combination with an inhibitor of thymidylate biosynthesis to enhance therapeutic efficacy. The motivation would have been to expand the options of the three drug combination and to develop better combinations for cancer treatment.
U.S. Patent No. 11,584,723
Claims 1, 3, 5-8, 21, 29, 31, 42, 43, 46, 48, 55 and 57-60 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,584,723 B2 (herein after Pat. 723) in view of Suzuki (Suzuki, EP3400963A1, Publication Date: 11/14/2018, cited in IDS of 12/15/2022) and Spyvee (Spyvee et al., WO 2017/006282 A1, Publication Date: 01/12/2017, cited in IDS of 12/15/2022).
The claims of Pat. 723 teach a compound of formula (I):
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Based on the definition of each component of formula (I), the compounds of Pat. 723 represent a subset of the compounds encompassed by the instant claim 1, 3, or 8. Because for each of A, L1, L2, L3 and B, the scope for the instant claim 1, 3 or 8 is broader than that of claim 1 of Pat. 723.
Claim 9 of Pat. 723 teaches that the compound of claim 1, wherein L1 can be:
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…
which read on the instant claim 43.
Claim 10 of Pat. 723 teach that the compound of claim 1, wherein L2 is -S(O)2NH- wherein the sulfur is attached to L1.
Claim 13 of Pat. 723 teach that the compound of claim 1, wherein L3 can be:
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which read on the instant claim 46.
Claim 7 of Pat. 723 teach that the compound of claim 1, wherein B is
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Based on the definition of claim 4, R20 is CH2-R21; methyl optionally substituted with 2 or 3 fluorine atoms; C3-C6 cycloalkyl; or C1-C6 alkyl; and R21 is C1-C10 alkyl optionally substituted with one or more hydroxy or fluoro; or C3-C6 cycloalkyl…. Taken together, claim 7 of Pat. 723 read on the instant claim 48 and overlap with the scope of instant claims 55 and 57.
Claim 16 of Pat. 723 teaches a method of treating a disease in a patient whose treatment is impeded by the expression or over expression of dUTPase, comprising:
administering to the patient in need of such treatment a therapeutically effective amount of the compound of claim 1, wherein the disease is cancer (claim 17), wherein the cancer is selected from the group consisting of colon cancer, colorectal cancer, gastric cancer, esophageal cancer, head and neck cancer, breast cancer, lung cancer, stomach cancer, liver cancer, gall bladder cancer, pancreatic cancer and leukemia (claim 18).
Claim 19 of Pat. 723 teaches a method of inhibiting the growth of a cancer cell comprising contacting the cell with a therapeutically effective amount of the compound of claim 1; and a therapeutically effective amount of a dUTPase directed therapeutic, thereby inhibiting the growth of the cancer cell; wherein the cancer cell is selected from a colon cancer cell, a colorectal cancer cell, a gastric cancer cell, a head and neck cancer cell, a breast cancer cell, a lung cancer cell or a blood cell (claim 20).
Taken together, the claims of Pat. 723 teach methods of treating cancers, or inhibiting cancer cell growth with dUTPase inhibitors of Formula (I). However, the claims of Pat. 723 do not teach using the dUTPase in combination with inhibitor of thymidylate biosynthesis (such as S-1 or 5-FU) and an immunotherapy agent (such as anti-PD-1 antibody), as instantly claimed.
Suzuki and Skyvee’s teachings are described above. In particular, Suzuki teaches a combination of a dUTPase inhibitor (compound I), an inhibitor of thymidylate biosynthesis (S-1), and an anti-PD-1 antibody, shows enhanced anti-tumor activity (Table 10), in a colorectal carcinoma model (CMT-93 tumor model). Suzuki teaches that the three drug combination was found to have a statistically significant effect of combination use to any other two drug combination ([0113], Example 4, Fig. 16, Table 10). Skyvee teaches dUTPase inhibitors of Formula (I) (such as compound A) and the method of making these compounds. Spyvee teaches that the dUTPase inhibitor can be used in combination with an agent which is suitable for treating the disease ([0173]), such as 5-FU, capecitabine, S-1 ([0301] and [0302]).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to use dUTPase inhibitor of Formula (I) to treat cancer or inhibit cancer cell growth as taught by the claims of Pat. 723 and to modify the method and to use the inhibitor in combination with an inhibitor of thymidylate biosynthesis (such as S-1, or 5-FU), and an anti-PD-1 antibody as taught by Suzuki and Skyvee. One of ordinary skill in the art would have had a reasonable expectation that the combination (such as the compound of taught by the claims of Pat. 723 + S-1 + anti-PD1 antibody) would be able to treat and inhibit cancer and to enhance the therapeutic efficacy because the combination of a dUTPase inhibitor, an inhibitor of thymidylate biosynthesis, and an anti-PD-1 antibody showed enhanced anti-tumor activity, Compound of Formula (I) (such as compound A) is a well-known dUTPase inhibitor as taught by Suzuki and Spyvee. One of ordinary skill in the art would have a reasonable expectation to reach the claimed invention because references teaches that the method can be modified for different embodiments; the method of producing the dUTPase inhibitors (such as compound A) is known; dUTPase inhibitors can be used in treating and inhibiting cancers (e.g. colorectal cancer); dUTPase inhibitors can be used in combination with an inhibitor of thymidylate biosynthesis to enhance therapeutic efficacy. The motivation would have been to expand the options of the three drug combination and to develop better combinations for cancer treatment.
U.S. Patent No. 12,098,133
Claims 1, 3, 5-8, 21, 29, 31, 42, 43, 46, 48, 55 and 57-60 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 12,098,133 B2 (herein after Pat. 133) in view of Suzuki (Suzuki, EP3400963A1, Publication Date: 11/14/2018, cited in IDS of 12/15/2022) and Spyvee (Spyvee et al., WO 2017/006282 A1, Publication Date: 01/12/2017, cited in IDS of 12/15/2022).
The claims of Pat. 133 teach a compound of Formula (I) of structure shown below (see claims 1 and 10):
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It is noted that the compound above is identical to the first compound listed in the instant claim 57 (the elected species). This compound is the same as Compound A used in the Examples of the instant Application (see paragraph [0590] of the instant publication US 2023/0263773 A1). As set forth above, the compound of Pat. 133 reads on the dUTPase inhibitor of all pending claims, such as claims 1, 3, 8, 42, 43, 46, 48, 55, 57.
The claims of Pat. 133 teach a method of treating a disease in a patient comprising administering a compound of Formula (I) (a dUTPase inhibitor), such as the compound shown above (claims 1, 10 and 15); wherein the disease is a cancer (claim 16), wherein the cancer can be colon cancer, colorectal cancer, gastric cancer, esophageal cancer, head and neck cancer, breast cancer, lung cancer, stomach cancer, liver cancer, gall bladder cancer, pancreatic cancer or leukemia (claim 17).
The claims of Pat. 133 teach a method of inhibiting the growth of a cancer cell comprising contact the cell with a compound of Formula (I) (a dUTPase inhibitor), such as the compound shown above (claims 1, 10 and 18), wherein the cancer cell is selected from a colon cancer cell, a colorectal cancer cell, a gastric cancer cell, a head and neck cancer cell, a breast cancer cell, a lung cancer cell or a blood cell (claim 19).
Taken together, the claims of Pat. 133 teach methods of treating cancers, or inhibiting cancer cell growth with dUTPase inhibitors of Formula (I), including the elected compound of the instant application. However, the claims of Pat. 133 do not teach using the dUTPase in combination with inhibitor of thymidylate biosynthesis (such as S-1 or 5-FU) and an immunotherapy agent (such as anti-PD-1 antibody), as instantly claimed.
Suzuki and Skyvee’s teachings are described above. In particular, Suzuki teaches a combination of a dUTPase inhibitor (compound I), an inhibitor of thymidylate biosynthesis (S-1), and an anti-PD-1 antibody, shows enhanced anti-tumor activity (Table 10), in a colorectal carcinoma model (CMT-93 tumor model). Suzuki teaches that the three drug combination was found to have a statistically significant effect of combination use to any other two drug combination ([0113], Example 4, Fig. 16, Table 10). Skyvee teaches the method of making Compound A. Spyvee teaches that the dUTPase inhibitor can be used in combination with an agent which is suitable for treating the disease ([0173]), such as 5-FU, capecitabine, S-1 ([0301] and [0302]).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to use dUTPase inhibitor such as compound A to treat cancer or inhibit cancer cell growth as taught by the claims of Pat. 133 and to modify the method and to use the inhibitor in combination with an inhibitor of thymidylate biosynthesis (such as S-1, or 5-FU), and an anti-PD-1 antibody as taught by Suzuki and Skyvee. One of ordinary skill in the art would have had a reasonable expectation that the combination (such as Compound A + S-1 + anti-PD1 antibody) would be able to treat and inhibit cancer and to enhance the therapeutic efficacy because the combination of a dUTPase inhibitor, an inhibitor of thymidylate biosynthesis, and an anti-PD-1 antibody showed enhanced anti-tumor activity, Compound A is a well-known dUTPase inhibitor as taught by Suzuki and Spyvee. One of ordinary skill in the art would have a reasonable expectation to reach the claimed invention because references teaches that the method can be modified for different embodiments; the method of producing Compound A is known; Compound A can be used in treating and inhibiting cancers (e.g. colorectal cancer); Compound A can be used in combination with an inhibitor of thymidylate biosynthesis. The motivation would have been to expand the options of the three drug combination and to develop better combinations for cancer treatment.
Application No. 18/807,770
Claims 1, 3, 5-8, 21, 29, 31, 42, 43, 46, 48, 55 and 57-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4-9, and 12-19 of copending Application No. 18/807,770 (hereinafter Appl. 770) in view of in view of Suzuki (Suzuki, EP3400963A1, Publication Date: 11/14/2018, cited in IDS of 12/15/2022) and Spyvee (Spyvee et al., WO 2017/006282 A1, Publication Date: 01/12/2017, cited in IDS of 12/15/2022).
The claims of Appl. 770 teaches a compound of Formula (I) (see claims 1, 2, 4-9 of Appl. 770) which has a scope overlapping with the instantly claimed compound of Formula (I).
The claims of Appl. 770 teach a method of treating a disease in a patient comprising administering a compound of Formula (I) as a dUTPase inhibitor (claim 15); wherein the disease is a cancer (claim 16), wherein the cancer can be colon cancer, colorectal cancer, gastric cancer, esophageal cancer, head and neck cancer, breast cancer, lung cancer, stomach cancer, liver cancer, gall bladder cancer, pancreatic cancer or leukemia (claim 17).
The claims of Appl. 770 teach a method of inhibiting the growth of a cancer cell comprising contact the cell with a compound of Formula (I) as a dUTPase inhibitor (claim 18), wherein the cancer cell is selected from a colon cancer cell, a colorectal cancer cell, a gastric cancer cell, a head and neck cancer cell, a breast cancer cell, a lung cancer cell or a blood cell (claim 19).
Taken together, the claims of Appl. 770 teach methods of treating cancers, or inhibiting cancer cell growth with dUTPase inhibitors of Formula (I) (a dUTPase inhibitor). However, the claims of Appl. 770 do not teach using the dUTPase in combination with inhibitor of thymidylate biosynthesis (such as S-1 or 5-FU) and an immunotherapy agent (such as anti-PD-1 antibody), as instantly claimed; or the specific dUTPase inhibitor: compound A (the elected species).
Suzuki and Skyvee’s teachings are described above. In particular, Suzuki teaches a combination of a dUTPase inhibitor (compound I), an inhibitor of thymidylate biosynthesis (S-1), and an anti-PD-1 antibody, shows enhanced anti-tumor activity (Table 10), in a colorectal carcinoma model (CMT-93 tumor model). Suzuki teaches that the three drug combination was found to have a statistically significant effect of combination use to any other two drug combination ([0113], Example 4, Fig. 16, Table 10). Skyvee teaches the specific inhibitor Compound A, the method of making Compound A. Spyvee teaches that the dUTPase inhibitor can be used in combination with an agent which is suitable for treating the disease ([0173]), such as 5-FU, capecitabine, S-1 ([0301] and [0302]).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to use dUTPase inhibitor of Formula (I) to treat cancer or inhibit cancer cell growth as taught by the claims of Appl. 770 and to modify the method and to use the inhibitor in combination with an inhibitor of thymidylate biosynthesis (such as S-1, or 5-FU), and an anti-PD-1 antibody as taught by Suzuki and Skyvee. One of ordinary skill in the art would have had a reasonable expectation that the combination (such as Compound A + S-1 + anti-PD1 antibody) would be able to treat and inhibit cancer and to enhance the therapeutic efficacy because the combination of a dUTPase inhibitor, an inhibitor of thymidylate biosynthesis, and an anti-PD-1 antibody showed enhanced anti-tumor activity, Compound A is a well-known dUTPase inhibitor as taught by Suzuki and Spyvee. One of ordinary skill in the art would have a reasonable expectation to reach the claimed invention because references teaches that the method can be modified for different embodiments; the method of producing Compound A is known; Compound A can be used in treating and inhibiting cancers (e.g. colorectal cancer); Compound A can be used in combination with an inhibitor of thymidylate biosynthesis. The motivation would have been to expand the options of the three drug combination and to develop better combinations for cancer treatment.
This is a provisional nonstatutory double patenting rejection.
Application No. 19/065,805
Claims 1, 3, 5-8, 21, 29, 31, 42, 43, 46, 48, 55 and 57-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of copending Application No. 19/065,805 (hereinafter Appl. 805) in view of in view of Suzuki (Suzuki, EP3400963A1, Publication Date: 11/14/2018, cited in IDS of 12/15/2022) and Spyvee (Spyvee et al., WO 2017/006282 A1, Publication Date: 01/12/2017, cited in IDS of 12/15/2022).
The claims of Appl. 805 teach a compound of Formula (I) of structure shown below (see claims 1 and 10):
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It is noted that the compound above is identical to the first compound listed in the instant claim 57 (the elected species). This compound is the same as Compound A used in the Examples of the instant Application (see paragraph [0590] of the instant publication US 2023/0263773 A1). As set forth above, the compound of Pat. 098 reads on the dUTPase inhibitor of all pending claims, such as claims 1, 3, 8, 42, 43, 46, 48, 55, 57.
The claims of Appl. 805 teach a method of treating a disease in a patient comprising administering a compound of Formula (I), such as the compound shown above (claims 1, 10 and 15); wherein the disease is a cancer (claim 16), wherein the cancer can be colon cancer, colorectal cancer, gastric cancer, esophageal cancer, head and neck cancer, breast cancer, lung cancer, stomach cancer, liver cancer, gall bladder cancer, pancreatic cancer or leukemia (claim 17).
The claims of Appl. 805 teach a method of inhibiting the growth of a cancer cell comprising contact the cell with a compound of Formula (I) (a dUTPase inhibitor), such as the compound shown above (claims 1, 10 and 18), wherein the cancer cell is selected from a colon cancer cell, a colorectal cancer cell, a gastric cancer cell, a head and neck cancer cell, a breast cancer cell, a lung cancer cell or a blood cell (claim 19).
Taken together, the claims of Appl. 805 teach methods of treating cancers, or inhibiting cancer cell growth with dUTPase inhibitors of Formula (I) (a dUTPase inhibitor), including the elected compound of the instant application. However, the claims of Pat. 133 do not teach using the dUTPase in combination with inhibitor of thymidylate biosynthesis (such as S-1 or 5-FU) and an immunotherapy agent (such as anti-PD-1 antibody), as instantly claimed.
Suzuki and Skyvee’s teachings are described above. In particular, Suzuki teaches a combination of a dUTPase inhibitor, an inhibitor of thymidylate biosynthesis (S-1), and an anti-PD-1 antibody, shows enhanced anti-tumor activity (Table 10), in a colorectal carcinoma model (CMT-93 tumor model). Suzuki teaches that the three drug combination was found to have a statistically significant effect of combination use to any other two drug combination ([0113], Example 4, Fig. 16, Table 10). Skyvee teaches the method of making Compound A. Spyvee teaches that the dUTPase inhibitor can be used in combination with an agent which is suitable for treating the disease ([0173]), such as 5-FU, capecitabine, S-1 ([0301] and [0302]).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to use dUTPase inhibitor such as compound A to treat cancer or inhibit cancer cell growth as taught by the claims of Appl. 805 and to modify the method and to use the inhibitor in combination with an inhibitor of thymidylate biosynthesis (such as S-1, or 5-FU), and an anti-PD-1 antibody as taught by Suzuki and Skyvee. One of ordinary skill in the art would have had a reasonable expectation that the combination (such as Compound A + S-1 + anti-PD1 antibody) would be able to treat and inhibit cancer and to enhance the therapeutic efficacy because the combination of a dUTPase inhibitor, an inhibitor of thymidylate biosynthesis, and an anti-PD-1 antibody showed enhanced anti-tumor activity, Compound A is a well-known dUTPase inhibitor as taught by Suzuki and Spyvee. One of ordinary skill in the art would have a reasonable expectation to reach the claimed invention because references teaches that the method can be modified for different embodiments; the method of producing Compound A is known; Compound A can be used in treating and inhibiting cancers (e.g. colorectal cancer); Compound A can be used in combination with an inhibitor of thymidylate biosynthesis. The motivation would have been to expand the options of the three drug combination and to develop better combinations for cancer treatment.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
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/CHENG LU/ Examiner, Art Unit 1642