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 1-11 are pending.
Domestic Benefit
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Instant application is a U.S. National Stage Entry of PCT/US2023/014589, filed 03/06/2023. PCT/US2023/014589 claims benefit of U.S. Provisional Application No. 63/317,281, filed 03/07/2022. Therefore, the effective filing date is 03/07/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/24/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Objections to the Specification
The disclosure is objected to because of the following informalities:
The specification, on page 43 line 15, reads “…but not compound sof the disclosure…” and should instead read “…but not compounds of the disclosure…”.
Appropriate correction is required.
Improper Markush Grouping
Claims 1-11 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of “dopamine D3 receptor agonists” in claims 1, 3, 4, 10, and 11, and the grouping of formulas (I), (II), 2,7-diamino-5-(4-fluorophenyl)-4-oxo-3,4,5,6-tetrahydropyrido[2,3-d]pyrimidine-6-carbonitrile, and (Z)-2-(1H-benzo[d]imidazol-2-yl)-N'-hydroxy-3-(4-methoxyphenyl) propanimidamide in claims 2 and 5-9, are 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 in these groups are only claiming to share a common use (the ability to prevent, treat, or ameliorate cocaine use disorder), and do not share a structural similarity.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112
The following is a quotation of 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 1-8, 10, and 11 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of preventing, treating, and/or ameliorating cocaine use disorder comprising administering a compound listed in instant claim 9, does not reasonably provide enablement for a method of preventing, treating, and/or ameliorating cocaine use disorder comprising administering any dopamine D3 receptor agonist or any compound of formulas (I) or (II). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
3- the presence or absence of working examples,
4- the nature of the invention,
5- the state of the prior art,
6- the relative skill of those in the art,
7- the predictability of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention
The nature of the invention relates to preventing, treating, or ameliorating cocaine use disorder comprising administering at least one “dopamine D3 receptor agonist”. The dopamine D3 receptor agonists also include, in claims 2 and 5-9, compounds of formula (I), formula (II), 2,7-diamino-5-(4-fluorophenyl)-4-oxo-3,4,5,6-tetrahydropyrido[2,3-d]pyrimidine-6-carbonitrile, and (Z)-2-(1H-benzo[d]imidazol-2-yl)-N'-hydroxy-3-(4-methoxyphenyl) propanimidamide.
Predictability of the art
The hypothetical compounds in claims 1 and 2 would be unpredictable in terms of one skilled in the art being able to synthesize every possible compound claimed in instant claims 1 and 2. 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 a 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.
Level of skill in the art
An ordinary artisan in the area of drug development would have experience in synthesizing and screening chemical compounds for particular activities, such as a medical doctor or chemist. Screening 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 often be employed, developing a therapeutic method, as claimed, is generally not well-known or routine, given the complexity of certain biological systems.
4. The breadth of the claims
The scope of the claims involves compounds that act as dopamine D3 receptor agonists. The scope additionally includes compounds of Formula (I), Formula (II), 2,7-diamino-5-(4-fluorophenyl)-4-oxo-3,4,5,6-tetrahydropyrido[2,3-d]pyrimidine-6-carbonitrile, and (Z)-2-(1H-benzo[d]imidazol-2-yl)-N'-hydroxy-3-(4-methoxyphenyl) propanimidamide, as shown in instant claim 2.
Claims 1 and 2 are very broad in the compounds, number of variables, and the options of substituents for each variable. There is an indefinite amount of hypothetical compounds included in claims 1 and 2.
5. The amount of direction provided, the presence or absence of working examples, and the quantity of experimentation necessary
The specification only provides structures for about 17 compounds, and biological data for about 10. The compounds tested or exemplified are listed in instant claim 9.
Synthesis methods are not taught in the specification to provide for the variables to include all of the possible substituents listed Formulas (I) and (II). It would be expected that, for example, the varying ring sizes (e.g., R1-R5) and heteroatoms in the rings (e.g., R1-R5) would change the reactivity of the compounds, and therefore would require synthesis methods not provided in the specification or claims. Additionally, no structure is provided for the “dopamine D3 receptor agonist” of instant claims 1, 3, 4, 11, and 11. It would require one skilled in the art, such as a chemist, to perform potentially thousands of reactions to determine which compounds of formulas (I) and (II) can be prepared, requiring synthesis methods other than those provided in the specification, and in vitro or in vivo testing to determine which of these compounds are capable of preventing, treating, or ameliorating cocaine use disorder. This is undue experimentation given the limited guidance and direction provided by Applicants.
Accordingly, the instant claims do not comply with the enablement requirement of 35 U.S.C. 112(a), since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
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 1-8, 10, and 11 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.
The inventor or joint inventor should note that claims 1, 3, 4, 11, and 11 are reach-through claims. The claim attempts to obtain protection for subject matter that is prophetic and/or has yet to be invented (dopamine D3 receptor agonists). Similarly, the metes and bounds of compounds capable of acting as dopamine D3 receptor agonists are not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. The specification does not structurally define dopamine D3 receptor agonists. Therefore, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the method for the treatment or prophylaxis cocaine use disorder comprising administering a “dopamine D3 receptor agonist” has been rendered indefinite by the use of the reach-through protocol.
Regarding claims 2 and 5-8, the phrase "substituted" renders the claim indefinite because the claims include elements not actually disclosed (those encompassed by "substituted"), thereby rendering the scope of the claims unascertainable. The specification only teaches, on page 18, non-limiting examples of substituents that are to be included in the instant claims. Therefore, the instant claims result in an indefinite number of possible compounds reading on Formulas (I) and (II).
Regarding claim 10, the phrase "additional agent" renders the claim indefinite because the claims include elements not actually disclosed, thereby rendering the scope of the claims unascertainable. The possible “additional agents” are not defined by either the claim or the specification, and it is unclear what the additional agent is meant to encompass. Therefore, the instant claim results in an indefinite number of possible compositions comprising an “additional agent”.
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.
Claims 1, 3, 4, and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Keck et al. (Identifying Medication Targets for Psychostimulant Addiction: Unraveling the Dopamine D3 Receptor Hypothesis, J. Med. Chem., 2015, Vol. 58, pages 5361-5380).
Keck et al. teaches, in the abstract, the development of medications comprising dopamine D3 receptor agonists to treat substance use disorder, specifically cocaine use disorder, as in instant claims 1, 3, and 11. The abstract also discusses the promising results regarding relapse behavior, indicating that the dopamine D3 receptor agonists reduce or eliminate the motivation for cocaine use, as in instant claim 4.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Keck et al. (cited above), as applied to claims 1, 3, 4, and 11 above.
Keck et al. teaches a method of treating/preventing cocaine use disorder comprising administering dopamine D3 receptor agonists.
Keck et al. fails to teach the combination of said D3 receptor agonists.
Regarding claim 10, it would be obvious to combine the dopamine D3 receptor agonists taught by Keck et al., which are independently taught to prevent/treat cocaine use disorder, in order to form a third composition for the same purpose. MPEP 2144.06 states: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)”.
Claims 1-11 are rejected under 35 U.S.C. 103 as being unpatentable over Kortagere et al. (WO 2012021629 A2).
Kortagere et al. teaches, in claim 1, a pharmaceutical composition comprising one or more compounds of Formulas (I), (II), 2,7-diamino-5-(4-fluorophenyl)-4-oxo-3,4,5,6-tetrahydropyrido[2,3-d]pyrimidine-6 carbonitrile, and (Z)-2-(lH-benzo[d]imidazol-2-yl)-N'-hydroxy-3-(4-methoxyphenyl)propanimidamide, as in instant claims 1, 2, 5-8, and 10. The compounds of reference claim 9 are the same as the compounds in instant claim 9.
Kortagere et al. fails to teach a specific embodiment where cocaine use disorder is prevented or treated.
However, Kortagere et al. teaches, on page 2, that the density of the D3 receptor is increased in chronic cocaine users. It is taught on pages 78-79 that: “Changes in D3 receptor expression … might provide explanations for some of the behavioral phenotypes observed in neurological disorders such as schizophrenia, psychosis, chronic cocaine use, stress, and depression. … The new class of atypical D3 receptor agonists described here … might provide a novel therapeutic approach to treat these disorders” (emphasis added).
Therefore, it would be prima facie obvious to one of ordinary skill in the art to use the “new class of atypical D3 receptor agonists” described by Kortagere et al. to treat or prevent cocaine use disorder, since Kortagere et al. explicitly suggests doing so.
One would have a reasonable expectation of success using the D3 receptor agonists taught in the prior art to prevent and treat cocaine use disorder since the prior art teaches that “the density of the D3 receptor is increased in chronic cocaine users”, and that these compounds are capable of acting as dopamine D3 receptor agonists, which would therefore prevent or treat the cocaine use disorder.
Regarding instant claim 4, the reduction or elimination of a subject’s motivation for cocaine use would be an inherent property of the method suggested and described by Kortagere et al. MPEP 2112 I states: “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).”
Conclusion
Claims 1-11 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RILLA M SAMSELL whose telephone number is (703)756-5841. The examiner can normally be reached Monday-Friday, 7-3.
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/R.M.S./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
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