Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
The amendments to the claims filed November 30, 2022 are acknowledged and entered. Claims 1-20 are pending.
Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any of the errors of which applicant may become aware of in the specification.
Priority
This is a National Application which was filed November 30, 2022.
Information Disclosure Statement
Examiner notes that no Information Disclosure Statement has been filed. As a reminder, Applicants and other individuals substantially involved with the preparation and/or prosecution of the application have a duty to disclose to the office all information known to that individual to be material to patentability as defined in 37 CFR §1.56.
Election/Restriction
Applicant’s election of Group I (claims 1-11 and 16, drawn to a composition) and the species of Formula I corresponding to Formula XI (pictured below for convenience) in the reply filed on October 7, 2025 is acknowledged. Claims 12-15 and 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Therefore this restriction is considered proper and thus made FINAL.
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The elected species corresponds to Formula I wherein
R is H; R1 is substituted phenyl (phenyl substituted with CF3); R2 is a heteroaromatic ring corresponding to
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; and Linker comprises an amide and a phenyl group, and has the structure corresponding to
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. Claims 1-3, 7-8, 10-11 and 16 encompass the elected species.
The guidelines in MPEP § 803.02 provide that upon examination if prior art is found for the elected species, the examination will be limited to the elected species. Relevant portion of MPEP § 803.02 is provided here for convenience:
As an example, in the case of an application with a Markush-type claim drawn to the compound X-R, wherein R is a radical selected from the group consisting of A, B, C, D, and E, the examiner may require a provisional election of a single species, XA, XB, XC, XD, or XE. The Markush-type claim would then be examined fully with respect to the elected species and any species considered to be clearly unpatentable over the elected species. If on examination the elected species is found to be anticipated or rendered obvious by prior art, the Markush-type claim and claims to the elected species shall be rejected, and claims to the nonelected species would be held withdrawn from further consideration. A second action on the rejected claims can be made final unless the examiner introduces a new ground of rejection that is neither necessitated by applicant’s amendment of the claims nor based on information submitted in an information disclosure statement filed during the period set forth in 37 CFR 1.97(c) with the fee set forth in 37 CFR 1.17(p). See MPEP § 706.07(a).
If the elected species or group of patentably indistinct species is not anticipated by or obvious over the prior art, the examiner should extend the search and examination to a non-elected species or group of species that falls within the scope of a proper Markush grouping that includes the elected species. The search and examination should be continued until either (1) prior art is found that anticipates or renders obvious a species that falls within the scope of a proper Markush grouping that includes the elected species, or (2) it is determined that no prior art rejection of any species that falls within the scope of a proper Markush grouping that includes the elected species can be made. The examiner need not extend the search beyond a proper Markush grouping. In other words, the examiner need not extend the search to any additional species that do not share a single structural similarity and a common use with the elected species (i.e., do not belong to the same recognized physical or chemical class or to the same art-recognized class and/or do not have a common use and/or do not share a substantial structural feature of a chemical compound and a use that flows from the substantial structural feature). The examiner should continue examination of the Markush claim to determine whether it meets all other requirements of patentability (e.g., 35 U.S.C. 101 and 112, nonstatutory double patenting, and proper Markush grouping).
The elected species was not found in the prior art and the search was expanded to include the subgenus of Formula I wherein
R is H; R1 is substituted or unsubstituted phenyl; R2 is a heteroaromatic ring; and Linker comprises an amide group and an aromatic group wherein the N atom of the amide group bonds to phenyl (i.e.
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).
And art was found. Claims 1-3, 7-8, 10-11 and 16 encompass the elected species read on the expanded subgenus.
Claims 4-6 and 9 (in full) and claims 1-3, 7-8, 10-11 and 16 (all in part, other than the above indicated subgenus) are additionally withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species.
Improper Markush Grouping Rejection
Claims 1-3, 7-8, 10-11 and 16 are rejected on the basis that they contain an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 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.
The Markush grouping of R, R1, R2 and Linker 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:
The compounds embraced by the scope of Formula I are not all members of the same recognized physical or chemical class or the same art-recognized class. The claims are drawn to compounds comprising many different heterocyclic and carbocyclic groups which do not overlap. For instance, R1 can be a phenyl group; an alkyl group; a substituted phenyl group; an aromatic ring; a heteroaromatic ring; a fused bicyclic group; a biphenyl group; or a 3-7 membered carbocyclic or alicyclic ring incorporating at least one heteroatom; R2 is selected from a phenyl group; a substituted phenyl group; an aromatic ring; a heteroaromatic ring; a bicyclic group; a tricyclic group; a 3-7 membered alicyclic ring incorporating at least one heteroatom; a carbocyclic ring; or a disubstituted carbocyclic ring; and Linker comprises at least one of an amide group; a reverse amide group; an ether group; an alkyl group; or a 3-7 membered carbocyclic, alicyclic, heterocyclic, aromatic, or heteroaromatic. The claims thus include many distinct compounds which are not classified together. The only structural feature which is required by the claims is
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; however, this is not substantial structural feature and there is no evidence to suggest the use of the compounds flow from this substructure. The claims are thus drawn to an improper Markush group.
Note, the rejection may be overcome by amending claims consistent with the elected species.
Claim Rejections - 35 USC § 112a
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, 7, 10-11 and 16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for Formula I wherein R is H or C1 alkyl; R1 is phenyl optionally substituted with halogen or trifluoromethyl, R2 is selected from
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;
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;
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;
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or
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, and Linker is a structure corresponding to
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or
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, does not reasonably provide enablement for Formula I comprising the full scope of the Linker, R, R1 and R2 claimed.
The specification is not adequately enabling for the scope of the compounds claimed. The only useful compounds are those embodiments disclosed at [0045] and [0047] of the specification and which are included in the subgenus of Formula I indicated above. This narrow scope of compounds does not give a reasonable assurance that all, or substantially all of the compounds within the scope of the claim are useful. The claims are not drawn in terms of a recognized genus but are directed to a more or less artificial selection of compounds. There is no reason why a claim drawn in this way should not be limited to those compounds which are shown to be useful. An Applicant is not entitled to a claim for a large group of compounds merely on the basis of a showing that a selected few are useful and a general suggestion of a similar utility in the others. There is no statement of utility beyond that for inhibition of of LDH (see e.g. Fig 3). Ex parte Lanham, 108 USPQ at 135 states “It was never intended that a patent be granted upon a product, or a process producing a product, unless such product be useful.”
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the application coupled with information known in the art without undue experimentation. (United States v. Teletronics Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based on a single factor, but rather a conclusion reached by weighing many factors (See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). These factors include the following:
1) Amount of guidance provided by applicant. The Applicant has demonstrated the embodiments at [0045] and [0047] and which are described by the above indicated subgenus of Formula I, are inhibitors of LDH and have activity against pancreatic cancer cells (see Figs 4, 5 and 6). However, there is no evidence to show the full scope of Formula I which includes thousands of structurally diverse compounds have any use.
2) The nature of the invention and predictability in the art. It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F. 2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. Pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, “the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved”. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
3) Number of working examples. A compound of Formula I wherein R is H or C1 alkyl; R1 is phenyl optionally substituted with halogen or trifluoromethyl, R2 is selected from
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;
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;
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;
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or
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, and Linker is a structure corresponding to
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or
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represents a narrow subgenus for which applicant has provided sufficient guidance regarding how to use. However, this disclosure is not sufficient to allow extrapolation of the limited examples to enable the scope of the compounds instantly claimed. Applicant has provided no working examples of any compounds, compositions, or pharmaceutically acceptable salts of Formula I beyond the narrow subgenus indicated above.
Within the specification, “specific operative embodiments or examples of the invention must be set forth, Examples 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).
4) Scope of the claims. The scope of the claims involves all of the thousands of compounds of the following formula:
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Thus, the scope of the claims is very broad.
5) Level of skill in the art. The artisan using applicant' s invention would be a scientist with a Ph.D. degree and having several years of research experience.
6) Undue experimentation. MPEP §2164.01 (a) states, "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)."
The conclusion is clearly justified here that applicant is not enabled for making these compounds
Claim Rejections - 35 USC § 112b
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 1-3, 7-8, 10-11 and 16 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. [A] claim is indefinite when the boundaries of the protected subject matter are not clearly delineated and the scope is unclear (MPEP 2173.04). The following terms and/or phrases render the scope of the claims unclear because the specification does not provide a scope limiting definition of the phrase or term, or any direction for ascertaining the scope of the limitation indicated by the term or phrase. Accordingly, one skilled in the art could not ascertain the metes and bounds of the claimed invention.
Claim 1 is drawn to a composition; however, the claim only requires a compound of Formula I. A composition requires a carrier. Examiner suggests amending the claim to insert a “carrier” after the term “comprising”.
Claim 1 recites the phrase “Linker comprises” which renders the claim indefinite because the term “comprises” is open ended (see MPEP 2111.03 Transitional Phrases) and therefore the structure of what Applicant regards as a “Linker” of the claims is not clear. The metes and bounds of the claim cannot be determined because a person skilled in the art has no way of knowing what other groups may be included in the scope the claimed “Linker”. Examiner suggest amending the claims to recite “Linder consists of” to more clearly define the scope of Linker and Formula I.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 recites the broad recitation “aromatic”, and the claim also recites “phenyl”, “biphenyl” and “heteroaromatic” which are the narrower statement of the range/limitation “aromatic” (see definitions of R1, R2 and Linker; e.g. R1 is selected from phenyl; an aromatic ring; a heteroaromatic ring, a biphenyl group. Phenyl, heteroaromatic and biphenyl are all within the broad definition “aromatic”); claim 1 further recites the broad recitation “carbocyclic”, and the claim also recites “phenyl” which is the narrower statement of the limitation (see definitions of R2); claim 1 further recites the broad recitation “heterocyclic”, and the claims also recites “heteroaromatic” which is the narrower statement of the limitation (see definitions of Linker); claim 1 further recites the broad recitation “carbocyclic” and the claim also recites “alicyclic” which is the narrow statement of the range limitation (see definition of Linker). The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Examiner suggests amending the claims to recite specific aromatic groups for which Applicant has written support.
Claim 1 recites the limitation “substituted” (e.g. substituted phenyl). The limitation “substituted” renders the claims unclear at each occurrence throughout the claims because no substituents are provided in the claim and the specification fails to provide a scope limiting definition of substituents. One skilled in the art could not say which substituents are included in the scope of the claim and therefore the metes and bounds of the invention. Examiner suggests amending the claim to recite specific substituents which are supported by the specification.
Claim 1 recites the limitations “bicyclic group” and “tricyclic group”. The limitations are indefinite because the specification does not provide any direction for ascertaining which bicyclic and tricyclic groups are regarded as part of the invention. Moreover, a “bicyclic” or “tricyclic” group is open to different interpretations and could be understood to mean fused rings or rings connect through single bonds (e.g. Ph-Ph), or both. The metes and bounds of the invention cannot be ascertained. Examiner suggests amending the claim to recite specific groups for which Applicant has written support.
Claim 1 recites R2 is a “carbocyclic ring” which renders the claim indefinite because it is not clear which sizes of rings or nature of the ring (e.g. aromatic or non-aromatic) are included in the scope of the limitation.
Claim 1 recites “heterocyclic” and “heteroaromatic” which are indefinite because ring size and heteroatom number and type are not indicated. The metes and bounds of the invention cannot be determined.
Claim 1 recites the limitation “amide group” which is indefinite because the specification fails to provide any direction for identify what Applicant regards as an “amide group” of the invention. Such a group is open to multiple interpretations and therefore the metes and bound of the invention are unclear.
Claims 2-3, 7, 10-11 and 16 depend from claim 1, fail to cure all of the above mentioned deficiencies, and therefor are also indefinite.
Claim 8 is drawn to compounds of Formula I which teach wherein R2 is a substituted heteroaromatic ring (e.g. see Formulae IX, XI, XLV, LXXXVIII, and LXXXIX). There is insufficient antecedent basis for these compounds because claim 8 depends from claim 1 which does not allow for R2 to be a substituted heteroaromatic ring.
Claim 8 recites “The compound of claim 7” and should instead recite “The composition of claim 7” for the reason that claim 7 is drawn to a composition.
Claims 10 and 11 depend from claim 1 and recite the limitations “compound has an IC50” or “compound has a cellular viability”. These limitations are properties of the composition of claim 1 which do not further limit the structure of claim 1. Claims 10 and 11 are therefore duplicates of claim 1 and should be deleted.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1-2, 10-11 and 16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Field et al. (US 5,001,140)(hereinafter “Field”).
Field teaches a composition comprising (E)-4-[[3-[2-(Cyclobutyl-2-thiazolyl)ethenyl]phenyl]amino]-2-phenyl-4-oxobutanoic acid (col 20, Example 27, claim 7; compound pictured below for convenience) which corresponds to a compound represented by instant Formula I wherein R is H; R1 is phenyl; R2 is a heteroaromatic ring corresponding to
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; and Linker comprises an amide and a phenyl group.
Field teaches the claimed composition and therefore the composition would have the IC50 properties against LDHA and pancreatic cancer cells recited in instant claims 10-11.
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Claim(s) 1-3, 7-8 and 10-11 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chemical Abstract Services (Registry Number 1030765-84-4, 2008) (hereinafter “CAS”).
The instant claims recite a composition; however, the claimed composition only requires a compound of Formula I. CAS teaches RN 1030765-84-4 (pictured below for convenience) which corresponds to the claimed compound of Formula I regarded as Formula LXXXVIII (see claim 8). CAS teaches each and every limitation of the instant claims and therefore anticipates the invention. Moreover, CAS teaches Formula I and therefore the prior art compound would have the properties recited in claims 10-11 (e.g. IC50 against pancreatic cancer cells).
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Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KEVIN MARTIN whose telephone number is (571)270-0917. The examiner can normally be reached Monday - Friday 8 am - 5 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached on (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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November 6, 2025
/K.S.M./Examiner, Art Unit 1624
/BRUCK KIFLE/Primary Examiner, Art Unit 1624