DETAILED ACTION
Notice of Pre-AIA or AIA Status
The inventor or joint inventor should note that the instant invention, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 64, 75 and 79-81 are pending in the instant invention. According to the Amendments to the Claims, filed June 29, 2026, claims 64, 75 and 79 were amended and claims 1-63, 65-74, 76-78 and 82-89 were cancelled.
Status of Priority
This invention is a 35 U.S.C. § 371 National Stage Filing of International Application No. PCT/CA2022/051446, filed September 29, 2022, which claims priority under 35 U.S.C. § 119(e) to US Provisional Application Nos.: a) 63/316,746, filed March 4, 2022; and b) 63/249,878, filed September 29, 2021.
Although the inventor’s or joint inventor’s claim for the benefit of a prior-filed invention under 35 U.S.C. § 119(e) is acknowledged, the inventor or joint inventor has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. § 119(e) as follows:
The later-filed invention must be an invention for a patent, for an invention which is also disclosed in the prior-filed invention (the provisional invention). The disclosure of the invention in the prior-filed invention and in the later-filed invention must be sufficient to comply with the requirements of 35 U.S.C. § 112(a). {See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)}.
The specification of the prior-filed invention, US Provisional Application No. 63/249,878, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. § 112(a) for one or more claims of this invention for the following reason: the specification in the instant invention has been amended with respect to Structure Nos. 108-358, respectively, and is no longer coextensive with that of US Provisional Application No. 63/249,878.
Consequently, since the specification of US Provisional Application No. 63/249,878 lacks adequate support or enablement for one or more claims of the elected invention of Group I, as defined below in Restrictions / Election of Species, and in the manner provided by 35 U.S.C. § 112(a), the first Office action on the merits of all relevant claims drawn to Group I will be prosecuted according to the earliest effective filing date afforded this invention, which is that of US Provisional Application No. 63/316,746, filed March 4, 2022.
Restrictions / Election of Species
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The inventor’s or joint inventor’s provisional election of the following, without traverse, in the reply filed on June 29, 2026, is acknowledged: a) Group I - claims 64 and 75; and b) substituted heteroaryl carboxamide of formula (I) - p. 105, Compound 1, shown to the right below, and hereafter referred to as N-(5-((1R,2R)-2-(4-cyanophenyl)cyclopropyl)-1,3,4-thiadiazol-2-yl)-3-(5- fluoro-2-methoxyphenyl)isonicotinamide, where Y = -5-fluoro-2-methoxyphenyl; X = -pyridin-4-yl; V = N; W = -1,2,-cyclopropylene-; and Z = -4-cyanophenyl. Claims 64 and 75 read on the elected species. Affirmation of this election must be made by the inventor or joint inventor in replying to this Office action.
Similarly, the inventor or joint inventor should further note that the requirement is still deemed proper and is therefore made FINAL.
Likewise, the inventor or joint inventor should further note that the elected species, shown to the right above, was found to be free of the prior art.
Next, the inventor or joint inventor should further note that claim 64 is directed to allowable instantly recited substituted thiazolecarboxamides and 1,3,4-thiadiazolecarboxamides. Pursuant to the procedures set forth in MPEP § 821.04(b), claims 79-81, directed to a method of treating a subject in need thereof, comprising administering… an instantly recited substituted thiazolecarboxamide or 1,3,4-thiadiazolecarboxamide, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Then, the inventor or joint inventor should further note that since all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action, mailed on March 30, 2026, is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, the inventor or joint inventor is advised that if any claim presented in a continuation or divisional invention is anticipated by, or includes all the limitations of, a claim that is allowable in the present invention, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant invention.
Moreover, the inventor or joint inventor should further note that once the restriction requirement is withdrawn, the provisions of 35 U.S.C. § 121 are no longer applicable. {See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971); and MPEP § 804.01}.
Thus, a first Office action and prosecution on the merits of claims 64, 75 and 79-81 is contained within.
Specification Objection - Disclosure
The inventor or joint inventor is advised to format the specification according to 37 CFR 1.77(c). Revisions should particularly address bold-type, underline, and/or upper case formatting. Appropriate correction may be required.
Specification Objection - Title
The inventor or joint inventor is reminded of the proper content of the title of the invention.
The title of the invention should be brief, but technically accurate and descriptive and should contain fewer than 500 characters. See 37 CFR 1.72(a) and MPEP § 606.
The title of the invention is not technically accurate and descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. In the revised title, the examiner suggests identifying: a) the substituted heteroaryl carboxamides of the formula (I); and b) a particular utility for the substituted heteroaryl carboxamides of the formula (I).
The following title is suggested: SUBSTITUTED THIAZOLECARBOXAMIDES AND 1,3,4-THIADIAZOLECARBOXAMIDES FOR INHIBITING HUMAN POLYMERASE THETA.
Appropriate correction is required.
Claim Objections
Claim 64 is objected to because of the following informalities: a) for clarity and precision, A compound selected from should be replaced with A compound selected from the group consisting of; b) for clarity and precision, and should be inserted prior to No. 358; and c) a comma should be inserted after No. 358. Appropriate correction is required. See MPEP § 2173.02.
Claim 75 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 64, or a pharmaceutically acceptable salt thereof.
Appropriate correction is required. See MPEP § 2173.02.
Claim 79 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(a) and/or 35 U.S.C. § 112(b), the existing recitation should be replaced with the following recitation(s):
79. A method for modulating the activity of human polymerase theta (Polq) in a human subject in need thereof, wherein the method comprises administering to the human subject a therapeutically effective amount of the compound of claim 64, or a pharmaceutically acceptable salt thereof.
105. A method for modulating the activity of human polymerase theta (Polq) in a human subject in need thereof, wherein the method comprises administering to the human subject a therapeutically effective amount of the pharmaceutical composition of claim 75.
Appropriate correction is required. See MPEP § 2173.02.
Claim 80 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation(s):
80. The method of claim 79, wherein the human subject suffers from a cancer.
106. The method of claim 105, wherein the human subject suffers from a cancer.
Appropriate correction is required. See MPEP § 2173.02.
Claim 81 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation(s):
81. The method of claim 80, wherein the cancer is selected from the group consisting of (i), (ii), (iii), (iv), and (v):
(i) a carcinoma selected from the group consisting of acinous carcinoma, adenocarcinoma, adenocystic carcinoma, alveolar carcinoma, basal cell carcinoma, basosquamous cell carcinoma, bronchiolar carcinoma, bronchogenic carcinoma, carcinoma cutaneum, carcinoma durum, carcinoma en cuirasse, carcinoma epitheliale adenoides, carcinoma ex ulcere, carcinoma fibrosum, carcinoma in situ, carcinoma molle, carcinoma myxomatodes, carcinoma of the adrenal cortex, carcinoma ossificans, carcinoma sarcomatodes, carcinoma scroti, carcinoma simplex, carcinoma spongiosum, carcinoma telangiectaticum, cerebriform carcinoma, cholangiocellular carcinoma, chorionic carcinoma, comedo carcinoma, corpus carcinoma, cribriform carcinoma, cylindrical carcinoma, duct carcinoma, embryonal carcinoma, encephaloid carcinoma, epidermoid carcinoma, exophytic carcinoma, gelatinous carcinoma, giant cell carcinoma, glandular carcinoma, granulosa cell carcinoma, hair-matrix carcinoma, hematoid carcinoma, hepatocellular carcinoma, Hurthle cell carcinoma, hyaline carcinoma, hypernephroid carcinoma, intraepidermal carcinoma, intraepithelial carcinoma, Krompecher’s carcinoma, Kulchitzky-cell carcinoma, large-cell carcinoma, lenticular carcinoma, lipomatous carcinoma, lymphoepithelial carcinoma, medullary carcinoma, melanotic carcinoma, mucinous carcinoma, nasopharyngeal carcinoma, oat cell carcinoma, osteoid carcinoma, papillary carcinoma, periportal carcinoma, preinvasive carcinoma, prickle cell carcinoma, pultaceous carcinoma, renal cell carcinoma, reserve cell carcinoma, Schneiderian carcinoma, scirrhous carcinoma, signet-ring cell carcinoma, small-cell carcinoma, solanoid carcinoma, spheroidal cell carcinoma, spindle cell carcinoma, squamous cell carcinoma, string carcinoma, transitional cell carcinoma, tuberous carcinoma, and verrucous carcinoma.
(ii) a sarcoma selected from the group consisting of Abernethy’s sarcoma, adipose sarcoma, alveolar soft part sarcoma, ameloblastic sarcoma, angiosarcoma, botryoid sarcoma, chloroma sarcoma, chondrosarcoma, embryonal sarcoma, endometrial sarcoma, Ewing’s sarcoma, fascial sarcoma, fibroblastic sarcoma, giant cell sarcoma, granulocytic sarcoma, Hodgkin’s sarcoma, immunoblastic sarcoma of B-cells, immunoblastic sarcoma of T-cells, Kaposi’s sarcoma, Kupffer cell sarcoma, liposarcoma, leukosarcoma, lymphosarcoma, malignant mesenchymal sarcoma, melanosarcoma, myxosarcoma, osteosarcoma, parosteal sarcoma, reticulocytic sarcoma, Rous sarcoma virus, serocystic sarcoma, stromal sarcoma, synovial sarcoma, telangiectatic sarcoma, and Wilms’ tumor sarcoma;
(iii) a leukemia selected from the group consisting of acute granulocytic leukemia, acute promyelocytic leukemia, adult T-cell leukemia, aleukemic leukemia, basophylic leukemia, blast cell leukemia, bovine leukemia virus, chronic granulocytic leukemia, chronic lymphocytic leukemia, chronic myelocytic leukemia, embryonal leukemia, eosinophilic leukemia, Gross' leukemia, hairy-cell leukemia, hemocytoblastic leukemia, histiocytic leukemia, leukemia cutis, leukopenic leukemia, lymphatic leukemia, lymphocytic leukemia, lymphosarcoma cell leukemia, mast cell leukemia, megakaryocytic leukemia, micromyeloblastic leukemia, monocytic leukemia, multiple myeloma, myeloblastic leukemia, myelocytic leukemia, myeloid granulocytic leukemia, Naegeli leukemia, nonlymphocytic leukemia, plasma cell leukemia, promyelocytic leukemia, Rieder cell leukemia, stem cell leukemia, subleukemic leukemia, and undifferentiated cell leukemia;
(iv) a melanoma selected from the group consisting of acral-lentiginous melanoma, amelanotic melanoma, Cloudman’s melanoma, Harding-Passey melanoma, juvenile melanoma, lentigo maligna melanoma, malignant melanoma, nodular melanoma, S91 melanoma, subungual melanoma, and superficial spreading melanoma; and
(v) brain cancer, breast cancer, cervical cancer, colon cancer, colorectal cancer, endocrine system cancer, endometrial cancer, esophageal cancer, genitourinary tract cancer, glioblastoma multiforme, glioma, head & neck cancer, kidney cancer, liver cancer, lung cancer, lymphoma, malignant hypercalcemia, medulloblastoma, melanoma, mesothelioma, multiple myeloma, a neoplasm of the exocrine pancreas, neuroblastoma, a premalignant skin lesion, primary brain tumor, primary macroglobulinemia, primary thrombocytosis, prostate cancer, rhabdomyosarcoma, stomach cancer, and urinary bladder cancer.
90. The method of claim 81, wherein the adenocarcinoma is villous adenocarcinoma.
91. The method of claim 81, wherein the alveolar carcinoma or bronchiolar carcinoma is bronchioalveolar carcinoma.
92. The method of claim 81, wherein the cylindrical carcinoma is cylindrical cell carcinoma.
93. The method of claim 81, wherein the embryonal carcinoma is infantile embryonal carcinoma.
94. The method of claim 81, wherein the medullary carcinoma is medullary thyroid carcinoma.
95. The method of claim 81, wherein the medullary thyroid carcinoma is familial medullary thyroid carcinoma.
96. The method of claim 81, wherein the epidermoid carcinoma or mucinous carcinoma is mucoepidermoid carcinoma.
97. The method of claim 81, wherein the monocytic leukemia is acute monocytic leukemia or myelomonocytic leukemia.
98. The method of claim 81, wherein the juvenile melanoma is benign juvenile melanoma.
99. The method of claim 81, wherein the endocrine system cancer is selected from the group consisting of adrenal cortical cancer, a malignant carcinoid, ovarian cancer, pancreatic cancer, testicular cancer, thyroid cancer, and uterine cancer.
100. The method of claim 99, wherein the pancreatic cancer is malignant pancreatic insulinoma or a neoplasm of the endocrine pancreas.
101. The method of claim 99, wherein the thyroid cancer is medullary thyroid carcinoma or papillary thyroid cancer.
102. The method of claim 81, wherein the liver cancer is hepatocellular carcinoma.
103. The method of claim 81, wherein the lung cancer is non-small cell lung cancer.
104. The method of claim 81, wherein the lymphoma is Hodgkin’s lymphoma or non-Hodgkin’s lymphoma.
107. The method of claim 106, wherein the cancer is selected from the group consisting of (i), (ii), (iii), (iv), and (v):
(i) a carcinoma selected from the group consisting of acinous carcinoma, adenocarcinoma, adenocystic carcinoma, alveolar carcinoma, basal cell carcinoma, basosquamous cell carcinoma, bronchiolar carcinoma, bronchogenic carcinoma, carcinoma cutaneum, carcinoma durum, carcinoma en cuirasse, carcinoma epitheliale adenoides, carcinoma ex ulcere, carcinoma fibrosum, carcinoma in situ, carcinoma molle, carcinoma myxomatodes, carcinoma of the adrenal cortex, carcinoma ossificans, carcinoma sarcomatodes, carcinoma scroti, carcinoma simplex, carcinoma spongiosum, carcinoma telangiectaticum, cerebriform carcinoma, cholangiocellular carcinoma, chorionic carcinoma, comedo carcinoma, corpus carcinoma, cribriform carcinoma, cylindrical carcinoma, duct carcinoma, embryonal carcinoma, encephaloid carcinoma, epidermoid carcinoma, exophytic carcinoma, gelatinous carcinoma, giant cell carcinoma, glandular carcinoma, granulosa cell carcinoma, hair-matrix carcinoma, hematoid carcinoma, hepatocellular carcinoma, Hurthle cell carcinoma, hyaline carcinoma, hypernephroid carcinoma, intraepidermal carcinoma, intraepithelial carcinoma, Krompecher’s carcinoma, Kulchitzky-cell carcinoma, large-cell carcinoma, lenticular carcinoma, lipomatous carcinoma, lymphoepithelial carcinoma, medullary carcinoma, melanotic carcinoma, mucinous carcinoma, nasopharyngeal carcinoma, oat cell carcinoma, osteoid carcinoma, papillary carcinoma, periportal carcinoma, preinvasive carcinoma, prickle cell carcinoma, pultaceous carcinoma, renal cell carcinoma, reserve cell carcinoma, Schneiderian carcinoma, scirrhous carcinoma, signet-ring cell carcinoma, small-cell carcinoma, solanoid carcinoma, spheroidal cell carcinoma, spindle cell carcinoma, squamous cell carcinoma, string carcinoma, transitional cell carcinoma, tuberous carcinoma, and verrucous carcinoma.
(ii) a sarcoma selected from the group consisting of Abernethy’s sarcoma, adipose sarcoma, alveolar soft part sarcoma, ameloblastic sarcoma, angiosarcoma, botryoid sarcoma, chloroma sarcoma, chondrosarcoma, embryonal sarcoma, endometrial sarcoma, Ewing’s sarcoma, fascial sarcoma, fibroblastic sarcoma, giant cell sarcoma, granulocytic sarcoma, Hodgkin’s sarcoma, immunoblastic sarcoma of B-cells, immunoblastic sarcoma of T-cells, Kaposi’s sarcoma, Kupffer cell sarcoma, liposarcoma, leukosarcoma, lymphosarcoma, malignant mesenchymal sarcoma, melanosarcoma, myxosarcoma, osteosarcoma, parosteal sarcoma, reticulocytic sarcoma, Rous sarcoma virus, serocystic sarcoma, stromal sarcoma, synovial sarcoma, telangiectatic sarcoma, and Wilms’ tumor sarcoma;
(iii) a leukemia selected from the group consisting of acute granulocytic leukemia, acute promyelocytic leukemia, adult T-cell leukemia, aleukemic leukemia, basophylic leukemia, blast cell leukemia, bovine leukemia virus, chronic granulocytic leukemia, chronic lymphocytic leukemia, chronic myelocytic leukemia, embryonal leukemia, eosinophilic leukemia, Gross' leukemia, hairy-cell leukemia, hemocytoblastic leukemia, histiocytic leukemia, leukemia cutis, leukopenic leukemia, lymphatic leukemia, lymphocytic leukemia, lymphosarcoma cell leukemia, mast cell leukemia, megakaryocytic leukemia, micromyeloblastic leukemia, monocytic leukemia, multiple myeloma, myeloblastic leukemia, myelocytic leukemia, myeloid granulocytic leukemia, Naegeli leukemia, nonlymphocytic leukemia, plasma cell leukemia, promyelocytic leukemia, Rieder cell leukemia, stem cell leukemia, subleukemic leukemia, and undifferentiated cell leukemia;
(iv) a melanoma selected from the group consisting of acral-lentiginous melanoma, amelanotic melanoma, Cloudman’s melanoma, Harding-Passey melanoma, juvenile melanoma, lentigo maligna melanoma, malignant melanoma, nodular melanoma, S91 melanoma, subungual melanoma, and superficial spreading melanoma; and
(v) brain cancer, breast cancer, cervical cancer, colon cancer, colorectal cancer, endocrine system cancer, endometrial cancer, esophageal cancer, genitourinary tract cancer, glioblastoma multiforme, glioma, head & neck cancer, kidney cancer, liver cancer, lung cancer, lymphoma, malignant hypercalcemia, medulloblastoma, melanoma, mesothelioma, multiple myeloma, a neoplasm of the exocrine pancreas, neuroblastoma, a premalignant skin lesion, primary brain tumor, primary macroglobulinemia, primary thrombocytosis, prostate cancer, rhabdomyosarcoma, stomach cancer, and urinary bladder cancer.
108. The method of claim 107, wherein the adenocarcinoma is villous adenocarcinoma.
109. The method of claim 107, wherein the alveolar carcinoma or bronchiolar carcinoma is bronchioalveolar carcinoma.
110. The method of claim 107, wherein the cylindrical carcinoma is cylindrical cell carcinoma.
111. The method of claim 107, wherein the embryonal carcinoma is infantile embryonal carcinoma.
112. The method of claim 107, wherein the medullary carcinoma is medullary thyroid carcinoma.
113. The method of claim 107, wherein the medullary thyroid carcinoma is familial medullary thyroid carcinoma.
114. The method of claim 107, wherein the epidermoid carcinoma or mucinous carcinoma is mucoepidermoid carcinoma.
115. The method of claim 107, wherein the monocytic leukemia is acute monocytic leukemia or myelomonocytic leukemia.
116. The method of claim 107, wherein the juvenile melanoma is benign juvenile melanoma.
117. The method of claim 107, wherein the endocrine system cancer is selected from the group consisting of adrenal cortical cancer, a malignant carcinoid, ovarian cancer, pancreatic cancer, testicular cancer, thyroid cancer, and uterine cancer.
118. The method of claim 117, wherein the pancreatic cancer is malignant pancreatic insulinoma or a neoplasm of the endocrine pancreas.
119. The method of claim 117, wherein the thyroid cancer is medullary thyroid carcinoma or papillary thyroid cancer.
120. The method of claim 107, wherein the liver cancer is hepatocellular carcinoma.
121. The method of claim 107, wherein the lung cancer is non-small cell lung cancer.
122. The method of claim 107, wherein the lymphoma is Hodgkin’s lymphoma or non-Hodgkin’s lymphoma.
Appropriate correction is required. See MPEP § 2173.02.
Claim Rejections - 35 U.S.C. § 112(a)
Method of treating a subject in need thereof, comprising administering… an instanlty recited substituted heteroaryl carboxamide of the formula (I)
Claims 79-81 are rejected under 35 U.S.C. § 112(a) as failing to comply with the enablement requirement because the claims contain subject matter, particularly a method of treating a subject in need thereof, comprising administering… an instantly recited substituted heteroaryl carboxamide, which was not described in the specification in such a way as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use (perform) the invention commensurate in scope with these claims.
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. These factors include, but are not limited to: (a) breadth of the claims; (b) nature of the invention; (c) state of the prior art; (d) level of one of ordinary skill in the art; (e) level of predictability in the art; (f) amount of direction provided by the inventor or joint inventor; (g) existence of working examples; and (h) quantity of experimentation needed to make or use the invention based on the content of the disclosure. {See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986); and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988)}.
The above factors, regarding the present invention, are summarized as follows:
(a) Breadth of the claims - the breadth of the claims includes a method of treating a subject in need thereof, comprising administering… an instantly recited substituted heteroaryl carboxamide;
(b) Nature of the invention - the nature of the invention is performance of a method of treating a subject in need thereof, comprising administering… an instantly recited substituted heteroaryl carboxamide;
(c) State of the prior art - Nature Reviews: Drug Discovery offers a snapshot of the state of the drug development art. Herein, drug development is stated to follow the widely accepted Ehrlich model which includes: (1) development of a broad synthetic organic chemistry program; (2) subsequent testing of compounds in an appropriate laboratory model for the disease to be treated; and (3) screening of compounds with low toxicity in prospective clinical trials (Jordan, V. C. Nature Reviews: Drug Discovery, 2, 2003, 205). Similarly, no single drug has been discovered that is effective in treating the myriad of pre-malignant conditions and/or diseases or conditions having the symptoms of cell hyperproliferation, including, but not limited to, cancer {See In re Hokum, 226 USPQ 353 (ComrPats 1985)}. Moreover, WO 23/050007, as provided in the file and cited on the IDS, illustrates the synthesis of substituted heteroaryl carboxamides of the formula (I), and/or methods of use thereof {Liu, et al. WO 23/050007, 2023};
(d) Level of one of ordinary skill in the art - the artisans performing the inventor’s or joint inventor’s method of treating a subject in need thereof, comprising administering… an instantly recited substituted heteroaryl carboxamide would be a collaborative team of synthetic chemists and/or health practitioners, possessing commensurate degree level and/or skill in the art, as well as several years of professional experience;
(e) Level of predictability in the art - Synthetic organic chemistry is quite unpredictable (See In re Marzocchi and Horton 169 USPQ at 367 ¶3). Similarly, it is well established that [T]he scope of enablement varies inversely with the degree of unpredictability of the factors involved, and physiological activity is generally considered to be an unpredictable factor {See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970)}.
Moreover, the following excerpt is taken from Hackam, et al., with respect to the poor replication of animal research in human clinical trials {Hackam, et al. JAMA, 296(14), 2006, 1731-1732}:
Only about a third of highly cited animal research translated at the level of human randomized trials. This rate of translation is lower than the recently estimated 44% replication rate for highly cited human studies. Nevertheless, we believe these findings have important implications. First, patients and physicians should remain cautious about extrapolating the findings of prominent animal research to the care of human disease. Second, major opportunities for improving study design and methodological quality are available for preclinical research. Finally, poor replication of even high-quality animal studies should be expected by those who conduct clinical research.
(f) Amount of direction provided by the inventor - the invention lacks direction with respect to making and/or using (performing) a method of treating a subject in need thereof, comprising administering… an instantly recited substituted heteroaryl carboxamide;
(g) Existence of working examples - the disclosure is insufficient to allow extrapolation of the limited examples to enable performing the instantly recited method of treating a subject in need thereof, comprising administering… an instantly recited substituted heteroaryl carboxamide.
Similarly, according to the specification, the instantly recited substituted heteroaryl carboxamides are capable of treating a variety of pre-malignant conditions and/or diseases or conditions having the symptoms of cell hyperproliferation, including, but not limited to, cancer; however, the specification fails to set forth any convincing in vitro and/or in vivo assays corroborating the alleged activity in association with any pre-malignant conditions and/or diseases or conditions having the symptoms of cell hyperproliferation, including, but not limited to, cancer. There is insufficient disclosure to reasonably conclude that the method of treating a subject in need thereof, comprising administering… an instantly recited substituted heteroaryl carboxamide, as recited, would contribute to treatment of any pre-malignant conditions and/or diseases or conditions having the symptoms of cell hyperproliferation, including, but not limited to, cancer. Furthermore, the combination of the instant specification and Liu, et al. in WO 23/050007, as provided in the file and cited on the IDS, lacks adequate credible evidence to support the assertion that a method of treating a subject in need thereof, comprising administering… an instantly recited substituted heteroaryl carboxamide, as recited, would contribute to the prophylaxis of any pre-malignant conditions and/or diseases or conditions having the symptoms of cell hyper-proliferation, including, but not limited to, cancer, since the inventor or joint inventor has neither provided convincing data for any patient population, nor indicated any art recognized correlation between the disclosed data and the breadth of the claims.
Within the specification, [A]t least one specific operative embodiment or example of the invention must be set forth. The example(s) and description should be of sufficient scope as to justify the scope of the claims. Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula. See MPEP § 608.01(p) and MPEP § 2173.05.
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(h) Quantity of experimentation needed to make and/or use (perform) the invention based on the content of the disclosure - predicting whether a recited compound is in fact one that produces a desired physiological effect at a therapeutic concentration and with useful kinetics, is filled with experimental uncertainty, and without proper guidance, would involve a substantial amount of experimentation (Jordan, V. C. Nature Reviews: Drug Discovery, 2, 2003, 205-213). Furthermore, it is unclear, based on the guidance provided by the specification, whether an instantly recited substituted heteroaryl carboxamide, such as N-(5-((1R,2R)-2-(4-cyanophenyl)cyclopropyl)-1,3,4-thiadiazol-2-yl)-3-(5-fluoro-2-methoxyphenyl)isonicotinamide, shown to the left above, possesses utility as a therapeutic agent, useful in a method of treating a subject in need thereof, comprising administering… an instantly recited substituted heteroaryl carboxamide. Thus, one of ordinary skill in the art, at the time this invention was made, would have an unreasonable expectation of success and undue experimentation in transferring the in vitro and/or in vivo method of treating a subject in need thereof, comprising administering… an instantly recited substituted heteroaryl carboxamide, wherein the pre-malignant condition and/or disease or condition having the symptoms of cell hyperproliferation, includes, but is not limited to, cancer, to any human subject population.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the invention was filed, would not have taught one skilled in the art how to make and/or use (perform) the full scope of the claimed invention without undue experimentation. {See In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)}.
The determination that undue experimentation would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations. (See In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404). These factual considerations are discussed comprehensively in MPEP § 2164.08 (scope or breadth of the claims), § 2164.05(a) (nature of the invention and state of the prior art), § 2164.05(b) (level of one of ordinary skill), § 2164.03 (level of predictability in the art and amount of direction provided by the inventor or joint inventor), § 2164.02 (the existence of working examples) and § 2164.06 (quantity of experimentation needed to make or use the invention based on the content of the disclosure).
Based on a preponderance of the evidence presented herein, the conclusion that the inventor or joint inventor is insufficiently enabled for making and/or using (performing) a method of treating a subject in need thereof, comprising administering… an instantly recited substituted heteroaryl carboxamide is clearly justified.
The examiner suggests amending the claims, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Claim Rejections - 35 U.S.C. § 112(b)
The following is a quotation of the second paragraph of 35 U.S.C. § 112:
(b) CONCLUSION. The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or joint inventor regards as the invention.
Claim 79 is rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that claim 79 fails to explicitly recite a targeted disease or condition for the method of treating a subject in need thereof, comprising administering… an instantly recited substituted heteroaryl carboxamide, which renders the claim indefinite.
Similarly, the inventor or joint inventor should further note that the specification does not provide an adequate standard for ascertaining the requisite degree of any targeted disease or condition for the method of treating a subject in need thereof, comprising administering… an instantly recited substituted heteroaryl carboxamide, and thus, one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention.
Moreover, the inventor or joint inventor should further note that the specification, on page 1, discloses cancer as a targeted disease or condition for the method of treating a subject in need thereof, comprising administering… an instantly recited substituted heteroaryl carboxamide; however, neither the specification, nor the claim explicitly limits the invention to this specific or preferred embodiment.
Consequently, the inventor or joint inventor should further note that the method of treating a subject in need thereof, comprising administering… an instantly recited substituted heteroaryl carboxamide has been rendered indefinite by the lack of a targeted disease or condition for the method of treating a subject in need thereof, comprising administering… an instantly recited substituted heteroaryl carboxamide.
The examiner suggests amending the claim, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Claim 81 is rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that claim 81 recites the limitation, …(ii) a sarcoma selected from the group consisting of… choriocarcinoma, Jensen’s sarcoma (rat)… and lymphoma. There is insufficient antecedent basis, in claim 81, for this limitation, with respect to the method of treating a subject in need thereof, comprising administering… an instantly recited substituted heteroaryl carboxamide. According to claim 81, choriocarcinoma, Jensen’s sarcoma (rat), and lymphoma, respectively, are not recited as either sarcomas or a human sarcoma, with respect to the method of treating a subject in need thereof, comprising administering… an instantly recited substituted heteroaryl carboxamide.
The examiner suggests amending the claim, particularly as stated in the section above entitled Claim Objections, to overcome this section of the rejection.
Similarly, the inventor or joint inventor should further note that a broad limitation together with a narrow limitation that falls within the broad limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c), MPEP § 2173.05(h), and/or Eli Lilly & Co. v. Teva Parenteral Meds., 845 F.3d 1357, 1371, 121 USPQ2d 1277, 1287 (Fed. Cir. 2017).
Likewise, the inventor or joint inventor should further note that claim 81 recites the broad limitations, (1) adenocarcinoma; (2) alveolar carcinoma or bronchiolar carcinoma; (3) cylindrical carcinoma; (4) embryonal carcinoma; (5) medullary carcinoma; (6) medullary thyroid carcinoma; (7) epidermoid carcinoma or mucinous carcinoma; (8) monocytic leukemia; (9) juvenile melanoma; (10) endocrine system cancer; (11) pancreatic cancer; (12) thyroid cancer; (13) liver cancer; (14) lung cancer; and (15) lymphoma, respectively, and the claim also recites (1) villous adenocarcinoma; (2) bronchioalveolar carcinoma; (3) cylindrical cell carcinoma; (4) infantile embryonal carcinoma; (5) medullary thyroid carcinoma; (6) familial medullary thyroid carcinoma; (7) mucoepidermoid carcinoma; (8) acute monocytic leukemia or myelomonocytic leukemia; (9) benign juvenile melanoma; (10) adrenal cortical cancer, a malignant carcinoid, ovarian cancer, pancreatic cancer, testicular cancer, thyroid cancer, and uterine cancer; (11) malignant pancreatic insulinoma or a neoplasm of the endocrine pancreas; (12) medullary thyroid carcinoma or papillary thyroid cancer; (13) hepatocellular carcinoma; (14) non-small cell lung cancer; and (15) Hodgkin’s lymphoma or non-Hodgkin’s lymphoma; respectively, which are the narrower statements of the limitations.
Next, the inventor or joint inventor should further note the explanation given by the Board of Patent Appeals and Interferences in Ex parte Wu, 10 USPQ2d 2031, 2033 (Bd. Pat. App. & Inter. 1989), pertaining to where broad language is followed by such as and then narrow language. The Board stated that this can render a claim indefinite by raising a question or doubt as to whether the feature introduced by such language is (a) merely exemplary of the remainder of the claim, and consequently, not required, or (b) a required feature of the claim.
Moreover, the inventor or joint inventor should further note the explanation given by the Board of Patent Appeals and Interferences in the decisions of Ex parte Steigewald, 131 USPQ 74 (Bd. App. 1961); Ex parte Hall, 83 USPQ 38 (Bd. App. 1948); and Ex parte Hasche, 86 USPQ 481 (Bd. App. 1949).
The examiner suggests amending the claim, particularly as stated in the section above entitled Claim Objections, to overcome this section of the rejection.
Allowable Subject Matter
No claims are allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DOUGLAS M. WILLIS, whose telephone number is 571-270-5757. The examiner may normally be reached on Monday thru Thursday from 8:00-6:00 EST. The examiner is also available on alternate Fridays.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Mr. Jeffrey Murray, may be reached on 571-272-9023. The fax phone number for the organization where this invention or proceeding is assigned is 571-273-8300.
Information regarding the status of an invention may be obtained from Patent Center. For more information about Patent Center, see https://www.uspto.gov/patents/apply/patent-center. Should you have questions on access to Patent Center, contact the Patent Electronic Business Center (PEBC) at 866-217-9197 (toll-free) or ebc@uspto.gov.
/DOUGLAS M WILLIS/
Primary Examiner, Art Unit 1624
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