DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1, 6, 16, 38, 40, 46, 70, 102, 118-119, 138-139, 150-151, 171, 200, 204-205, 208, and 210 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1, 6, 16, 38, 40, 46, and 204, drawn to a compound of Formula (I) and pharmaceutical compositions thereof in the reply filed on May 04, 2026 is acknowledged.
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Applicant’s election without traverse of compound 1, depicted below, as the species of group I in the reply filed on May 04, 2026 is acknowledged.
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This is a compound of Formula (I) wherein:
Y is O;
Z is C1 alkylene substituted with one R2 selected as OH;
R1 is OH;
R5 is H;
and one of R6 and R7 is C1 alkyl and the other is halogen (Cl).
Because the compounds of formula (II) in group II, 70, 102, 118-119, 138-139, 150-151, and 171, and group III, claim 200, all read on instant formula (I), the restriction requirement has been expanded to include claims 70, 102, 118-119, 138-139, 150-151, 171, and 200.
Compound 1 is also a compound of Formula (II), depicted below:
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wherein:
R1 is OH;R2 is OH;
n is 1;
R5 is H;
and one of R6 and R7 is C1 alkyl and the other is halogen (Cl).
Compound 1 is also recited in claim 200.
Compound 1 has been found free of the prior art. Thus, examination has been expanded to the following compound (herein compound PT-47):
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Compound PT-47 is a compound of instant Formula (I) wherein: Y is NR4a where R4a is C1 alkyl;
Z is C1 alkyl;
R1 is NR3R4 where one of R3 is C1 alkyl and the other is hydrogen;
and one of R6 and R7 is halogen (Cl) and the other is hydrogen.
Claims 205, 208, and 210 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 04, 2026.
Claims 16, 40, 151, and 171 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 04, 2026.
Claims 1, 6, 38, 46, 70, 102, 118-119, 138-139, 150, 200, and 204 are under examination as they relate to compounds of Formula (I), Formula (II), and compounds from claim 200, as well as the elected species of compound 1 and expanded species of compound PT-47.
Claim Rejections – Improper Markush
A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
Claims 1, 6, 38, 46, 70, 102, 118-119, 138-139, 150, and 204 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 1059, 1060 (Bd. Pat. App. & Int. 1984).
The Markush grouping of compounds represented by the formula recited in Claim 1 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 Markush grouping is directed to compounds of Formula (I) or a pharmaceutically acceptable salt thereof:
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The variables R1, Y, Z, R5, R6, and R7 encompass a myriad of substituents forming compounds so diverse, that they will confer the above structure complete different structural and biological properties. Moreover, these variables can be substituted with R3, R4, R3A, R4A, Y1, R8, R9, and R10 substituents which would confer the above structure with completely different structural and biological properties. For example, R3, R4, and R4A may be C1-C10 alkyl, C6-C10 aryl, and R3A may be the following ring system
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with its own diverse set of substituents. With the myriad of compounds that arise from the various definitions and combinations of the variables present in this formula, the result is a group of compounds that include distinct ring systems and a variety of substitution patterns resulting in compounds with no single structural similarity that are not obvious variants of each other. To this end, a comparison of compounds of Formula (I) presented in the instant disclosure demonstrates a lack of significant structural similarity and shows compounds of the formula recited in instant Claim 1 are not obvious variants of each other:
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(compound 40, p. 53 of specification)
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(compound 2, recited in claim 200)
As these compounds demonstrate, the compounds according to the Formula (I) include compounds with no common core structure that are not obvious variants of each other. With no significant structural similarity, the Markush grouping is improper.
Although claims 6, 38, 46, and 204, which depend on claim 1, narrow the scope of the compounds of Formula (I), they still nonetheless each embody a diverse set of compounds that are not obvious variants of each other.
The Markush grouping of compounds represented by the formula recited in Claim 70 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 Markush grouping is directed to compounds of Formula (II) or a pharmaceutically acceptable salt thereof:
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The variables R1, R2, R5, R6, and R7 encompass a myriad of substituents forming compounds so diverse, that they will confer the above structure complete different structural and biological properties. Moreover, these variables can be substituted with R3, R4, R8, R9, and R10 substituents which would confer the above structure with completely different structural and biological properties. For example, R3 and R4 may be C1-C10 alkyl, C6-C10 aryl, or 5-10 membered heteroaryl, and R1 may be the following ring system
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with its own diverse set of substituents. With the myriad of compounds that arise from the various definitions and combinations of the variables present in this formula, the result is a group of compounds that include distinct ring systems and a variety of substitution patterns resulting in compounds with no single structural similarity that are not obvious variants of each other. To this end, a comparison of compounds of Formula (II) presented in the instant disclosure demonstrates a lack of significant structural similarity and shows compounds of the formula recited in instant Claim 70 are not obvious variants of each other:
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(compound 40, p. 53 of specification)
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(compound 2, recited in claim 200)
As these compounds demonstrate, the compounds according to the Formula (II) include compounds with no common core structure that are not obvious variants of each other. With no significant structural similarity, the Markush grouping is improper.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112112(a) – Scope of Enablement
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, 6, 38, 46, 70, 102, 118-119, 138-139, 150 and 204 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a compound of Formula (I) wherein:
Z is C1-C6 alkylene substituted with one R2 selected as OH;
R3, R4, and R4A are selected from hydrogen and C1-C6 alkyl optionally substituted with 1-6 halogens;
R5, R6, R7, R8, R9, and R10- are selected from hydrogen, halogen, and C1-C6 alkyl optionally substituted with 1-6 halogens;
and Y, Y1, R1, and R2 are substituted as described;
and for a compound of Formula (II) wherein:
R3 and R4 are selected from hydrogen and C1-C6 alkyl optionally substituted with 1-6 halogens;
R5, R6, R7, R8, R9, and R10- are selected from hydrogen, halogen, and C1-C6 alkyl optionally substituted with 1-6 halogens;
and R1 and R2 are substituted as described;
does not reasonably provide enablement for the full scope of variables Y, Y1, Z, R1, R2, R3, R4, R3A, R4A, R5, R6, R7, R8, R9, and R10- in the instant claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to compounds of Formulas (I) and (II) or a pharmaceutically acceptable salt thereof.
Breadth of the invention:
The scope of the claimed invention is very broad, as it is drawn to compounds of the formula:
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as well as the related formula:
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allowing for myriad combinations of variables and substitution patterns as described in the claims.
State of the prior art and predictability in the art:
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the 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).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F. 2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F. 2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F. 2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Tautermann (Quantum Mechanics in Drug Discovery, Humana Press, 2020, Chapter 1, pp. 1-17), cited for evidentiary purposes, teaches drug discovery is a very challenging, cost-intensive, and in terms of investment risky endeavor; on average, it takes 10–15 years and an investment of more than 2.5 billion dollars to get a new drug to the Market; especially the clinical phases cause extremely high costs and late-stage failures, especially in phase II studies, are quite common (page 1, 1st paragraph). Tautermann teaches the largest attrition in clinical phases is observed in phase II studies; the main goal is the assessment of the efficacy of the compound yielding a clinical proof of concept; a recent analysis from four major pharma companies revealed that the cause for attrition in phase II is mainly caused by lack of efficacy followed by safety issues; efficacy for a certain indication is usually preclinically tested in animal models; however, the translatability from animal models to the human situation is not always given; there are several reasons for this; often the disease condition cannot adequately be induced in animals (page 3, last paragraph). Tautermann teaches small molecules have several advantages, such as being cell and brain permeable, the lower cost of goods in their production, and oral administration; however, they are not always the easiest path forward for challenging targets; especially in the case of difficult or so far undruggable targets, new design strategies are required to be successful (page 5, last paragraph). Thus, Tautermann further establishes that the state of the art of drug design is highly unpredictable.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
The compound core depicted with specific substituents represents a narrow subgenus for which applicant has provided sufficient guidance to make and use; however, the disclosure is not sufficient to allow extrapolation of the limited examples to enable the scope of the compounds instantly claimed. As an example of the lack of enablement, Applicant has provided no working examples of any compounds, compositions, or pharmaceutically acceptable salts of compounds substituted with R3A as claimed. Although compounds 2 and 3 are embodied in the specification (p. 15) and are substituted with R3A, there are no experimental examples using these compounds. As another example Applicant has provided no working examples of any compounds, compositions, or pharmaceutically acceptable salts where any of R5, R6, R7, R8, R9, and R10- are anything other than methyl or halogen. In particular, these may be pseudohalogen as claimed, which as defined by the specification (p. 37, lines 6-9) refers to diverse substituents including but not limited to cyano, trifluromethanesulfonate, -OH, and azide, all of which may have different biological activities and challenges in synthesis. Finally, Applicant has provided no examples where any substituent is aryl or heteroaryl.
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).
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).” That conclusion is clearly justified here that Applicant is not enabled for making these compounds.
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 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Luo (CN 108947879 A; appended translated description on pp. 67-92 provided by Espacenet).
Regarding claim 1, Luo teaches compound PT-47 (p. 36, row 3 of table), depicted below.
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Compound PT-47 is a compound of instant Formula (I) wherein: Y is NR4a where R4a is C1 alkyl;
Z is C1 alkyl;
R1 is NR3R4 where one of R3 is C1 alkyl and the other is hydrogen;
and one of R6 and R7 is halogen (Cl) and the other is hydrogen.
Therefore, the reference anticipates the instantly claimed invention.
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.
Claims 1 and 204 are rejected under 35 U.S.C. 103 as being unpatentable over Luo (CN 108947879 A; appended translated description on pp. 67-92 provided by Espacenet).
As discussed above in this Office action (see rejections under 35 U.S.C. 102), Luo teaches compound PT-47, which is a compound of instant Formula (I).
Luo also teaches pharmaceutical compositions of their disclosed compounds (p. 67, para. 1; corresponding passage in original Chinese document found on p. 9, para. [0001]).
Regarding claim 1, because compound PT-47 anticipates instant Formula (I), it also renders it obvious.
Regarding claim 204, although Luo does not explicitly teach a pharmaceutical composition of compound PT-47, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date to do so. One would have been motivated and had a reasonable expectation of success since Luo teaches pharmaceutical compositions of their disclosed compounds.
Taken together, all this would result in the invention of instant claims 1 and 204, with a reasonable expectation of success.
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, 6, 38, and 46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 22 of copending Application No. 18/594,993 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claim renders obvious the instant claims.
Reference claim 22 teaches a method for detecting the affinity between stimulator of interferon genes (STING) and a compound selected from Table A. Compound 1 of Table A is depicted below (p. 40), which is the same as instantly elected compound 1:
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Although reference claim 22 does not explicitly teach a method of detecting the affinity of compound 1, it would have been obvious to select compound 1 because it is presented from a finite list of alternatives. Because compound 1 reads on instant Formulas (I) and (II) and is recited in instant claim 200, the use of compound 1 in the reference application reads on the instant claims 1, 6, 38, 40, 46, 70, 102, 118-119, 138-139, 150, and 200.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1, 6, 38, 40, 46, 70, 102, 118-119, 138-139, 150, 200, and 204 are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLIVER D. HEES whose telephone number is (571)272-9840. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm.
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/O.D.H./Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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