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 .1
Status of Claims
Claims 1-15 and 26-30 are pending and under examination.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement and Cited Background Art/Prior Art
The information disclosure statements (IDSs) submitted on Oct 4 2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
While a copy of Krystof et al. Perspective of Cyclin-dependent kinase 9 (CDK9) as a Drug Target Current Pharmaceutical Design. 2012, 13, 2883-2890, cited on the IDS, was provided to the Examiner, a new copy of Krystof et al. is being submitted to the prosecution file by the Examiner and cited on the PTO-892 form, as the Examiner had difficulty reading the copy on file with the USPTO.
As confirmed by the corresponding Written Opinion of PCT/EP2023/051250 and the Examiner’s own SciFinder searches, the claims are free of the prior art.
Claim Rejections - 35 USC § 112 (Written Description)
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 1-13, 15 and 26-30 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The Claimed Invention
The claimed invention (claim 1) is directed to a compound of formula I, where R1, R2 are R3, are broadly claimed. See below.
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or a salt or a solvate thereof.
Certain narrower embodiments of the claimed invention are presented in various dependent claims. Some of these claims further limit the claimed groups and substituents as detailed therein. Claim 14 recites the claimed and elected species and other individual species. Claim 14 is NOT rejected for written description.
The Supporting Disclosure
Applicants’ supporting disclosure contains certain descriptions and embodiments of the claimed invention.
In the present case, the important factors leading to a conclusion of inadequate written description is the absence of sufficient working examples of the invention as claimed, and the lack of predictability in the art.
In the present case there is no disclosure of compounds having the broad and full scope definitions of the groups and substituents of claim 1. In fact, the scope of compounds that provide adequate written description are the 27 compounds of claim 14 and examples 1-39 of specification, starting at page 28. (Also note the supporting biological data at pages 33-34).
In contrast to the broad claimed scope of R1, R2 are R3 of the claims, the supporting disclosure (claim 14, examples 1-39 starting at page 28, are limited to the following:
R1 is limited to cyclopentyl, cyclohexyl, piperidinyl, pyridinyl, imidazo[2,1-f ][1,2,4]
triazin-4-yl], pyridinyl-methyl, 1-cyclopentyl-4-piperidinyl, -N(CH3)2, morpholinyl, pyrrolidinyl, 4-piperidinylmethyl, 1-methyl-4-piperidinyl)methyl, 2-(4-morpholinyl)ethyl, 3-piperidinylmethyl, 1-methyl-2-piperidinyl)methyl, 1-ethyl-2-pyrrolidinyl)methyl, and 1-Piperidinecarboxylic acid,
where R1 is optionally substituted with 1-2 groups such as NH2, methyl, 1-methylethyl, -N-(2-fluoroethyl), -NH-ethanol, morpholinyl, 3-fluoropropyl, 4-methyl-1-piperazinyl, 2-methoxyethyl;
R2 is limited to 2,6-difluorophenyl, 2,6-dichlorophenyl, and 2-chloro-6-fluorophenyl;
R3 is limited to chloro.
Applicant’s disclosure of the 27 compounds of claim 14, examples 1-39 of specification, starting at page 28, and biological data at pages 33-34, is not a sufficient representation of all the claimed compounds of claim 1 (and rejected dependent claims) as presently pending.
Other than the working examples of the specification (27 compounds of claim 14, the specification’s examples and biological data), Applicant has not reasonably described a scientific or “systematic” approach to synthesize the full scope of claim 1 and claims dependent. See MPEP 2163.02, the standard for determining compliance with the written description.2
Although Applicant has written description support for the 27 compounds of claim 14 and also found in the specification, Applicant has not provided reasonably provided a description the support the broader scope of the claimed compounds of formula I.
Accordingly, Applicants have not adequately described the invention for the breadth that is claimed. It thus appears that Applicants were not in possession of the claimed invention at the time the application was filed, the full scope of compounds of formula I, and that Applicants’ species do not support the claimed genus.
Claim Rejections - 35 USC § 112 (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 26-30 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claims 26-30 are directed to methods of treating and preventing a subject in need of the multitude diseases recited therein, diseases of abnormal CDK9 regulation of claim 26; local or system viral infections of claim 27; non-solid/solid malignancies, cancers or hyperproliferative diseases of claim 28, or ANY combination of a disease of claim 26 per claim 29.
Applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set eight forth factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
The predictability or unpredictability of the art: The instant claimed invention is highly unpredictable since a person having ordinary skill in the art (PHOSITA) recognizes the unpredictability in treating the multitude of diseases claimed by CDK9 inhibition as claimed, let alone a single disease/disorder including the broad category of cancer.
Krystof et al.3 reports success of CDK9 inhibition anticancer activity, but does not recognize a single FDA approved CDK9 inhibitor drug against cancer or other disease at the time of its publication. See Discussion starting at page 2884 to 2885 for cancer discussion.
In fact, Krystof cautions that while CDK9 inhibition might precipitate immunosuppressive actions, leading to beneficial effects particularly in lymphocyte-driven disorders, it notes in vivo pharmacological investigations are needed to note the potential of CDK9 inhibition with regard to lymphocyte disorders. See Page 2886 column 2 to page 2887 column 1.
Further, Krystof concludes gaps in CDK9 inhibition knowledge to date have meant therapeutic application remains a long way off. See page 2887, CONCLUSION section. Krystof notes many CDK9 inhibitors are unselective, targeting several CDKs and other kinases, thus causing significant off-target associated toxicity, creating the need for more selective CDK9 inhibitors. Id.
Krystof notes a lack of in vivo models (only 2, arthritis, hepatitis) for testing. See page 2888 bridging to page 2889. Krystof teaches the need to confirm CDK9 is indeed the critical for induction of anti-inflammatory activity by CDK9 inhibitors in vivo. Id. at 2889. Krystof teaches “role of CDK9 in the respective disease-relevant cell types has to be revealed on a cellular .. functional and molecular mechanistic basis in much more detail in order to precisely understand its mode of action.” Id. at 2889.
Also note the Background of the Art on page 1 of the specification where at the time of the filing of the claimed invention, while several CDK9 specific inhibitors have entered pre-clinical and clinical trials, none have been FDA-approved for use in humans.
Accordingly, the unpredictability in the art is Wands factor against enablement of the claims to both treat and prevent the claimed diseases.
The breadth of the claims
The instant claims are deemed very broad as they recite the multitude of treating and preventing diseases, as well as combinations of said diseases, via CDK9 inhibition with the compounds of claim 1. Note that claim 1 and those dependent lack written description as detailed above. The broad scope is a Wands factors weighing against enablement of claims 26-30 to both treat and prevent these diseases.
The amount of direction or guidance presented, and the presence or absence of working examples
It has been established that “the amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” In re Fisher, 427 F.2d 833, 839 166 USPQ 18, 24 (CCPA 1970).
It is pointed out that there is no working example, either in vivo or in vitro to enable the treatment of any diseases or conditions via CDK9 inhibition, in Applicant’s specification.
Rather, the specification notes certain activity CDK9/Tl ADPGlo Activity, in vitro via Glo Detection Reagent, with Applicant’s Example compounds. See pages 33-34.
Therefore, in view of the Wands factors as discussed above, Applicant fails to provide information sufficient to practice the claimed invention as claimed to both treat and prevent the claimed diseases.
Claim Rejections - 35 USC § 112, 2nd paragraph
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 26, 28 and 29 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 26, 28 and 29, multiple occurrences of the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 26 and 28; line 13 of claim 26, line 9 of claim 28; the phrase "in particular" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 26, 28 and 29, multiple occurrences of the term "including" renders the claim indefinite because it is unclear whether the limitations following the term are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 112, 4th paragraph
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2 and 10 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 2 depends from claim 1, and recites R3 is CF3. However, claim 1 does not claim that the C1-4 alkyl of R3 is optionally substituted with halogen.
Claim 10 depends from claim 8 and recites R5 is NMe2, -NH(CH2)2F, -NH(CH2)3F, -NH(CH2)2OH, -NH(CH2)3OH, -NH(CH2)2OMe, -NH(CH2)3OMe, -N(Me)(CH2)2F, -N(Me)(CH2)3F, -N(Me)(CH2)2OH, -N(Me)(CH2)3OH, -N(Me)(CH2)2OMe, and -N(Me)(CH2)3OMe. However, claim 8 does NOT provide antecedent basis to allow claim 10 to recite those amino-type moieties for claim 10. Claim 8 only claims -NH2 (amino).
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Allowable Subject Matter
Claim 14 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion and Correspondence
In summary no claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM Y LEE/
Examiner, Art Unit 1623
/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621
1 CONTINUING DATA
This application is a 371 of PCT/EP2023/051250 01/19/2023
FOREIGN APPLICATIONS
EP 22152460.6 01/20/2022
2 Whenever the issue arises, the fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, inventor was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991). An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the inventor was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68,119 S.Ct. 304,312, 48 USPQ2d 1641, 1647 (1998); Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"
3 Krystof et al. Perspective of Cyclin-dependent kinase 9 (CDK9) as a Drug Target Current Pharmaceutical Design. 2012, 13, 2883-2890
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