DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1, 3, 7, 16, 23, 26, 32, 48 – 49, 53, 55, 57, 62, 64, 71, 75 – 79, and 82) drawn to a compound of Formula (I),
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wherein L, X, W, Z1-2, A, B, and R2 are defined and the species election of compound 122 of structure
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in the reply filed on July 7th, 2026 is acknowledged.
Claims 84, 86 – 87, and 91 – 92 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II (a method of forming a complex), Group III (a method of altering the conformation of a nucleic acid), and Group IV (a method for treating a disease or disorder), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 7th, 2026.
However, the initial search of the elected species of structure
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was found to be free of the prior art; therefore, the search was expanded to include the chemical specie of structure
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. Thus the election of species required in the Restriction Requirement mailed May 7th, 2026 is still maintained and the restriction between Groups I, Group II, Group III, and Group IV is maintained.
Hence claims 1, 3, 7, 16, 23, 26, 32, 48 – 49, 53, 55, 57, 62, 64, 71, 75 – 79, and 82 are being examined on the merits herein.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete.
Required response - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specific deficiency - The “Sequence Listing XML” has not been entered into the application because the required statement of no new matter, in accordance with 37 CFR 1.835(a)(4) or 1.835(b)(5), is missing.
Required response - Applicant must submit a statement that the “Sequence Listing XML,” identified by the date the “Sequence Listing XML” was filed, includes no new matter.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 75, 77, 79, and 82 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 75, the use of e.g., that is exampli gratia, which translates to “for example,” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Moreover, the use of the use of parenthesis in the claim renders the claim indefinite because it is unclear whether the recitation within the parenthesis are definitions or preferred embodiments. For example, the claim recites (e.g., bicyclic heteroaryl) is the compound required to have A and B independently a bicyclic heteroaryl or just an heteroaryl? As a consequence, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Specifically one of ordinary skill in the art would not be reasonably apprised of the structure of A and/or B. Therefore, given the uncertainty around the terms within the parenthesis claim 75 is rejected under 35 U.S.C. 112(b).
Regarding claim 77, that recites, “the compound of claim 1, wherein the compound is selected from a compound listed in Table 1,” in lines 1 – 2; without stating the chemical name or chemical structure. Applicant is reminded that, where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted). See MPEP 2173.05(s).
Regarding claim 79, that recites, “the compound of claim 17, or the pharmaceutical composition of claim 78, wherein the compound;” the claim recites a limitation dependent on claim 17, which is canceled. Thus, claim 79 lacks any antecedent basis for its limitations. See MPEP 2173.05(e). “If the base claim has been canceled, a claim which is directly or indirectly dependent thereon should be rejected as incomplete.” MPEP 608.01(n)(V). Therefore, given the uncertainty around the terms within the parenthesis claim 79 is rejected under 35 U.S.C. 112(b).
Regarding claim 82, the use of e.g., that is exampli gratia, which translates to “for example,” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Therefore, given the uncertainty around the terms within the parenthesis claim 82 is rejected under 35 U.S.C. 112(b).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3, 23, 26, 32, 48, 53, 78 – 79, and 82, are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by International Publication Number WO 2015/140717 A1 to Cauwenberghs et. al. (Cauwenberghs’717; cited on the ISR form).
Regarding claims 1, 3, 23, 26, 32, 48, 53, 78 – 79, and 82, Cauwenberghs’717 teach novel 3-(indol-3-yl)-pyridine derivatives useful as therapeutic compounds in the treatment and/or prevention of cancers. See page 1 lines 5 – 8. Specifically, Cauwenberghs’717 teach compounds of Formula (I) of structure
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. See Abstract. Moreover, Cauwenberghs’717 teach that A1, A2, and A3 each independently can be C, N, or O. See page 11 line 25. In particular, Cauwenberghs’717 teach the species compound number 18 of structure
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where L = absent; R2 = H; W = N; X = C(R3) where R3 = H; A = piperidine; Z1 = C(R3) where R3 = H; Z2 = C(R3) where R3 = H; and B = 1H-indole where R1 = F. See page 34 row 3. See claim 1 limitation for a compound of Formula (I)
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. See claim 3 limitation where B is a nitrogen-containing bicyclic heteroaryl. See claim 23 limitation where A is a nitrogen-containing monocyclic heterocyclyl. See claim 26 limitation where A =
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. See claim 32 limitation for a compound where A is
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. See claim 48 limitation for a compound R2 = H. See claim 53 limitation for a compound of Formula (I-a)
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and Formula (I-b)
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. Moreover, Cauwenberghs’717 teach that compound 18 had an IC50 of 948 nM against TDO2 enzymatic activity in potassium phosphate buffer (50 mM, pH 7.5). See page 245 lines 25 – 26 and page 246 Table lines 15 – 32. See claim 78 limitation for a pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient.
Regarding claim 79, limitation for the pharmaceutical composition of claim 78, where the compound: (i) alters a target nucleic acid; (ii) binds to a target nucleic acid; and/or (iii) stabilizes a target nucleic acid; Cauwenberghs’717 teach that compound 18 in potassium phosphate buffer. Since Cauwenberghs’717 teach that compound 18, a compound that anticipates claim 1, in potassium phosphate buffer, a pharmaceutical composition, would inherently alter a target nucleic acid; binds to a target nucleic acid; and/or stabilizes a target nucleic acid.
Regarding claim 82, limitation for the compound of claim 82, where the (a) the compound increases splicing at splice site on a target nucleic acid by about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or more, e.g., as determined by qPCR; or (b) the compound decreases splicing at splice site on a target nucleic acid by about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or more, e.g., as determined by qPCR; Cauwenberghs’717 teach compound 18 which contains all of the limitations of claim 1; compound would inherently increase splicing at splice site on a target nucleic acid or decreases splicing at splice site on a target nucleic acid.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 55, 57, 62, and 64 are rejected under 35 U.S.C. 103 as being unpatentable over International Publication Number WO 2015/140717 A1 to Cauwenberghs et. al. (Cauwenberghs’717; cited on the ISR form).
The teachings of Cauwenberghs’717 as they relate to claim 1, from which claims 55, 57, 62, and 64 depend, are given previously in this office action and are fully incorporated here.
However, Cauwenberghs’717 is silent about a specific embodiment where the compound of Formula (I) is a compound of either Formula (I-c) or Formula (I-d):
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. See claim 55 limitation. Moreover, Cauwenberghs’717 is silent about a specific embodiment where the compound of Formula (I) is a compound of Formula (I-e):
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. See claim 57 limitation. Furthermore, Cauwenberghs’717 is silent about a specific embodiment where the compound of Formula (I) is a compound of Formula (I-m) or Formula (I-q):
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or
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. See claim 62 limitation. Additionally, Cauwenberghs’717 is silent about a specific embodiment where the compound of Formula (I) is a compound of Formula (I-r):
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. See claim 64 limitation.
Nevertheless, Cauwenberghs’717 teach compounds of Formula (I) of structure
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. See Abstract. Moreover, Cauwenberghs’717 teach that A1, A2, and A3 each independently can be C, N, or O. See page 11 line 25. In particular, Cauwenberghs’717 teach the species compound number 18 of structure
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where L = absent; R2 = H; W = N; X = C(R3) where R3 = H; A = piperidine; Z1 = C(R3) where R3 = H; Z2 = C(R3) where R3 = H; and B = 1H-indole where R1 = F. See page 34 row 3. Given that the only difference between prior art compound number 18 of structure
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and a compound of claims 55, 57, 62, and 64 is the position of the N in the core bicyclic ring; both prior art compound 18 and a compound of claims 55, 57, 62, and 64 are positional isomers. Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See MPEP 2144.09 (II).
Claims 49, and 75 are rejected under 35 U.S.C. 103 as being unpatentable over International Publication Number WO 2015/140717 A1 to Cauwenberghs et. al. (Cauwenberghs’717; cited on the ISR form) as applied to claims 1, 3, 23, 26, 32, 48, 53, 55, 57, 62, 64,78 – 79, and 82 above, and further in view of Meanwell ((2011), Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design, J. Med. Chem., 54, 2529 – 2591).
The teachings of Cauwenberghs’717 as they relate to claim 1, from which claims 49, and 75 depend, are given previously in this office action and are fully incorporated here.
However, Cauwenberghs’717 is silent about a specific embodiment where the compound of claim 1 where R2 = CH3 or F. See claims 49 and 75 limitation.
Nevertheless, Meanwell teach that in the contemporary practice of medicinal chemistry, the development and application of bioisosteres have been adopted as a fundamental tactical approach useful to address a number of aspects associated with the design and development of drug candidates. See page 2529 column 1 paragraph 1. Additionally, Meanwell teach that bioisosteres are typically less than exact structural mimetics and are often more alike in biological rather than physical properties. See page 2529 column 1 paragraph 1. Moreover, Meanwell teach that F, H, and CH3 are classical monovalent bioisosteres. See page 2530 column 1 Table 1. Thus Meanwell suggest the ability to substitute F or CH3 for H with a reasonable expectation that compounds with either F, CH3, or H would have similar biological properties.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filling date of the instant application to modify compound 18 of Cauwenberghs’717 in view of Meanwell, that is to substitute the H atom for either a F atom or a CH3 group in the R2 position. One of ordinary skill in the art would be motivated to make this modification and have a reasonable expectation of success because F, H, and CH3 are classical monovalent bioisosteres and would be reasonable expected to at least have the same biological properties.
Claim 76 is rejected under 35 U.S.C. 103 as being unpatentable over International Publication Number WO 2015/140717 A1 to Cauwenberghs et. al. (Cauwenberghs’717; cited on the ISR form) as applied to claims 1, 3, 23, 26, 32, 48, 53, 55, 57, 62, 64,78 – 79, and 82 above, and further in view of Patani et. al. ((1996) Bioisosterism A rational approach in drug design, Chem. Rev., 96, 3147-3176).
The teachings of Cauwenberghs’717 as they relate to claim 1, from which claim 76 depends, is given previously in this office action and are fully incorporated here.
However, Cauwenberghs’717 is silent about a specific embodiment where the compound of claim 1 where Z1 = N. See claim 76 limitation.
Nevertheless, Patani et. al. teach that the concept of bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents. See page 3147 column 1 paragraph 1 and column 2 paragraph 1. Furthermore, Patani et. al. teach the ability of a group of bioisosteres to elicit similar biological activity has been attributed to common physicochemical properties. See page 3148 column 1 paragraph 2. Moreover, Patani et. al. teach that bioisosteres have been classified as either classical or nonclassical with classical bioisosteres have been traditionally divided into several distinct categories: (A) monovalent atoms or groups; (B) divalent atoms or groups; (C) trivalent atoms or groups; (D) tetrasubstituted atoms; and (E) ring equivalents. See page 3148 column 2 paragraph 4 and page 3149 column 1 paragraph 1. Specifically, Patani et. al. teach the trivalent substitution of -CH= with -N= is commonly used in modern drug design. See page 3159 column 2 paragraph 4. Moreover, Patani et. al. teach an example where a trivalent ring substitution of -CH= with -N= in the antibacterial agent norfloxacin (56a) resulted in enoxacin (56b, Figure 38) which is also in clinical use for its antibacterial activity. See page 3159 column 2 paragraph 4.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify compound 18 of Cauwenberghs’717 in view of Patani et. al. that is to have a trivalent ring substitution of Z1 from -CH= to -N=. One of ordinary skill in the art would have been motivated to make this modification to rationally modify compound 18 safer and more clinically effective agent. One of ordinary skill in the art would have had a reasonable expectation of success because the trivalent substitution of -CH= with -N= is commonly used in modern drug design. Moreover, in the prior art example where a trivalent ring substitution of -CH= with -N= in the antibacterial agent the bioisostere was also exhibited favorable biological affect.
Claims 7, 16, and 71 are rejected under 35 U.S.C. 103 as being unpatentable over International Publication Number WO 2015/140717 A1 to Cauwenberghs et. al. (Cauwenberghs’717; cited on the ISR form) as applied to claims 1, 3, 23, 26, 32, 48, 53, 55, 57, 62, 64,78 – 79, and 82 above, and further in view of Tung et. al. ((2011), Scaffold-Hopping Strategy: Synthesis and Biological Evaluation of 5,6-Fused Bicyclic Heteroaromatics To Identify Orally Bioavailable Anticancer Agents, J. Med. Chem., 54, 3076 – 3080) and Meanwell ((2011), Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design, J. Med. Chem., 54, 2529 – 2591).
The teachings of Cauwenberghs’717 as they relate to claim 1, from which claims 7, 16, and 71 depend, are given previously in this office action and are fully incorporated here.
However, Cauwenberghs’717 is silent about a specific embodiment where A and B are independently selected from
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. See claim 7 limitation. Moreover, Cauwenberghs’717 is silent about a specific embodiment where A and B are independently selected from
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. See claim 16 limitation. Furthermore, Cauwenberghs’717 is silent about a specific embodiment for a compound of Formula (I) that is a compound of Formula (I-u)
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. See claim 71 limitation.
Nevertheless, Tung et. al. teach the concept of scaffold-hopping as a medicinal chemistry method for molecular backbone replacements, is an important drug-design strategy that could be used to develop novel molecules with potent activity, altered physicochemical attributes, and ADMET properties, as well as molecules with new intellectual property (IP) positions. See page 3076 column 1 paragraph 1. Moreover, Tung et. al. teach that such drug-design strategies depend on the ability to synthesize new scaffolds in short, easy steps and are essentially chemistry-driven approaches. See page 3076 column 1 paragraph 1. Tung et. al. teach synthetic strategies for the replacement of the indole ring of 1 with alternative 5,6-fused bicyclic heteroaromatics to identify backup drug candidates with altered drug properties and new IP rights. See page 3076 column 1 paragraph 1. In particular, Tung et. al. teach a variety of scaffolds (1) by shuffling the nitrogen from the N-1 position to other positions of the indole moiety, leading to indolizine, and (2) by inserting one or two nitrogen atoms into the indole ring, leading to indazole, 7-azaindole, imidazo[1,2-a]pyridine, 7Hpyrrolo[2,3-d]pyrimidine, pyrazolo[1,5-b]pyridazine
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. See page 3076 column 1 paragraph 2 and page 3077 Figure 1. Thus Tung et. al. suggest that these 5,6-fused bicyclic n containing heteroaromatic scaffolds as alternatives. Hence given that the skill level of one of ordinary skill in the pharmaceutical and synthetic arts is relatively high; being that of master or Ph. D. it would have been within the purview of such artisan to attempt to synthesis additional lead compounds with improved pharmaceutical capabilities. Moreover, it would have been within the purview of such artisan to use the synthetic strategies of Tung et. al. for scaffold hopping to create a chemical species with one of A or B as recited in claims 7, 16 and encompassed in claim 71.
However, Tung et. al. is silent about a specific embodiment where A and B are independently selected from
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. See claim 16 limitation.
Nevertheless, Meanwell teach that in the contemporary practice of medicinal chemistry, the development and application of bioisosteres have been adopted as a fundamental tactical approach useful to address a number of aspects associated with the design and development of drug candidates. See page 2529 column 1 paragraph 1. Additionally, Meanwell teach that bioisosteres are typically less than exact structural mimetics and are often more alike in biological rather than physical properties. See page 2529 column 1 paragraph 1. Moreover, Meanwell teach that H, and CH3 are classical monovalent bioisosteres. See page 2530 column 1 Table 1. Thus Meanwell suggest the ability to substitute H for CH3 with a reasonable expectation that compounds with either CH3, or H would have similar biological properties.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filling date of the instant application to modify compound 18 of Cauwenberghs’717 in view of Tung et. al., that is to use scaffold hopping to substitute the Ring B indole for an imidazo[1,2‐b]pyridazine in further view of Meanwell, that is to substitute the H atom on the N for a CH3 group. One of ordinary skill in the art would be motivated to make this modification for alternative 5,6-fused bicyclic heteroaromatics to identify backup drug candidates with altered drug properties and new IP rights. And one of ordinary skill in the art would have a reasonable expectation of success because H, and CH3 are classical monovalent bioisosteres and would be reasonable expected to at least have the same biological properties.
Claim 77 is rejected under 35 U.S.C. 103 as being unpatentable over International Publication Number WO 2015/140717 A1 to Cauwenberghs et. al. (Cauwenberghs’717; cited on the ISR form) as applied to claims 1, 3, 23, 26, 32, 48, 53, 55, 57, 62, 64,78 – 79, and 82 above, and further in view of Tung et. al. ((2011), Scaffold-Hopping Strategy: Synthesis and Biological Evaluation of 5,6-Fused Bicyclic Heteroaromatics To Identify Orally Bioavailable Anticancer Agents, J. Med. Chem., 54, 3076 – 3080) and Meanwell ((2011), Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design, J. Med. Chem., 54, 2529 – 2591).
The teachings of Cauwenberghs’717 as they relate to claim 1, from which claim 77 depends, are given previously in this office action and are fully incorporated here.
However, Cauwenberghs’717 fails to teach a compound of claim 1 selected from a compound listed in Table 1 that is compound 105 of structure
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. See claim 77 limitation.
Nevertheless, one of the difference between prior art compound number 18 of structure
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and compound 105 is the position of the N in the core bicyclic ring; both prior art compound 18 and compound 105 are positional isomers. Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See MPEP 2144.09 (II).
However, Cauwenberghs’717 fails to teach a compound of claim 1 selected from a compound listed in Table 1 that is compound 105 of structure
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where ring B is a 2H-indazole substituted with a CH3 on the N. See claim 77 limitation.
Nevertheless, Tung et. al. teach the concept of scaffold-hopping as a medicinal chemistry method for molecular backbone replacements, is an important drug-design strategy that could be used to develop novel molecules with potent activity, altered physicochemical attributes, and ADMET properties, as well as molecules with new intellectual property (IP) positions. See page 3076 column 1 paragraph 1. Moreover, Tung et. al. teach that such drug-design strategies depend on the ability to synthesize new scaffolds in short, easy steps and are essentially chemistry-driven approaches. See page 3076 column 1 paragraph 1. Tung et. al. teach synthetic strategies for the replacement of the indole ring of 1 with alternative 5,6-fused bicyclic heteroaromatics to identify backup drug candidates with altered drug properties and new IP rights. See page 3076 column 1 paragraph 1. In particular, Tung et. al. teach a variety of scaffolds (1) by shuffling the nitrogen from the N-1 position to other positions of the indole moiety, leading to indolizine, and (2) by inserting one or two nitrogen atoms into the indole ring, leading to indazole, 7-azaindole, imidazo[1,2-a]pyridine, 7Hpyrrolo[2,3-d]pyrimidine, pyrazolo[1,5-b]pyridazine
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. See page 3076 column 1 paragraph 2 and page 3077 Figure 1. Thus Tung et. al. suggest that these 5,6-fused bicyclic N containing heteroaromatic scaffolds as alternatives. Hence given that the skill level of one of ordinary skill in the pharmaceutical and synthetic arts is relatively high; being that of master or Ph. D. it would have been within the purview of such artisan to attempt to synthesis additional lead compounds with improved pharmaceutical capabilities. Moreover, it would have been within the purview of such artisan to use the synthetic strategies of Tung et. al. for scaffold hopping to create a chemical species where ring B is a 2H-indazole.
However, Tung et. al. fails to teach a compound of claim 1 selected from a compound listed in Table 1 that is compound 105 of structure
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where ring B is a 2H-indazole is substituted with a CH3 on the N. See claim 77 limitation.
Nevertheless, Meanwell teach that in the contemporary practice of medicinal chemistry, the development and application of bioisosteres have been adopted as a fundamental tactical approach useful to address a number of aspects associated with the design and development of drug candidates. See page 2529 column 1 paragraph 1. Additionally, Meanwell teach that bioisosteres are typically less than exact structural mimetics and are often more alike in biological rather than physical properties. See page 2529 column 1 paragraph 1. Moreover, Meanwell teach that H, and CH3 are classical monovalent bioisosteres. See page 2530 column 1 Table 1. Thus Meanwell suggest the ability to substitute H for CH3 with a reasonable expectation that compounds with either CH3, or H would have similar biological properties.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filling date of the instant application to modify compound 18 of Cauwenberghs’717 in view of Tung et. al., that is to use scaffold hopping to substitute the Ring B indole for an 2H-indazole in further view of Meanwell, that is to substitute the H atom on the N for a CH3 group. One of ordinary skill in the art would be motivated to make this modification for alternative 5,6-fused bicyclic heteroaromatics to identify backup drug candidates with altered drug properties and new IP rights. And one of ordinary skill in the art would have a reasonable expectation of success because H, and CH3 are classical monovalent bioisosteres and would be reasonable expected to at least have the same biological properties.
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.
Claims 1, 3, 7, 16, 23, 26, 32, 48 – 49, 53, 55, 57, 62, 64, 71, 75 – 79, and 82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 10, 12 – 14, 18 – 19, 22, 25 – 30, 32, 36 – 38, 40, 45 – 49, 51, 54, 58, 67 – 73, 75 – 81, 91 – 96, and 111 – 116 of copending Application No. 19/492981 to Reynolds et. al. (Reynolds’981).
Reynolds’981 recite a compound of (reference) Formula (I):
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. See reference claim 1. See examined claim 1. Moreover, Reynolds’981 recite a compound of (reference) Formula (I) where ring A, Ring B, L1, L2, X, Y, W, Z1, Z2, Z3, Z4, and Z5 are defined and overlap with examined claims 3, 7, 16, 23, 26, 32, 48 – 49, 53, 55, 57, 62, 64, 71, 75 – 79, and 82. See reference claims 2 – 10, 12 – 14, 18 – 19, 22, 25 – 30, 32, 36 – 38, 40, 45 – 49, 51, 54, 58, 67 – 73, 75 – 81, 91 – 96, and 111 – 116. See examined claims 3, 7, 16, 23, 26, 32, 48 – 49, 53, 55, 57, 62, 64, 71, 75 – 79, and 82. Furthermore, Reynolds’981 recite a pharmaceutical composition comprising a compound of any of (reference) claims 1 – 90 and a pharmaceutically acceptable excipient. See reference claim 91. See examined claim 78. Additionally, Reynolds’981 recite a compound selected from a compound in Table 1. See reference claim 90.
However, Reynold’s fails to recite a compound where the L1 and Ring A is connected to the scaffold through reference X. See examined claims 1 and 77 limitations for a compound of Formula (I),
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.
Nevertheless, given that the only difference between copending (reference) Formula (I) of structure
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and examined Formula (I) of structure
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is the position of L1-Ring A; and given that copending X can be N(R2C) both copending (reference) Formula (I) and examined Formula (I) are positional isomers. Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See MPEP 2144.09 (II).
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 1, 3, 7, 16, 23, 26, 32, 48 – 49, 53, 55, 57, 62, 64, 71, 75 – 79, and 82 are rejected.
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/DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627
Prosecution Insights