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 .
DETAILED ACTION
Claims 1, 2, 4, 5, 7, 8, 10, 12, 17, 20, 22, 24, 28-31, 34 and 36-38 are currently pending in the instant application. Applicants have amended claims 2, 4, 5, 7, 8, 10, 12, 17, 20, 22, 24, 28-31, 34, 37 and 38 and canceled claims 3, 6, 9, 11, 13-16, 18-19, 21, 23, 25-27, 32-33 and 35 in an amendment filed on March 12, 2025. Claims 1, 2, 4, 8, 10, 12, 17, 20, 22, 24, 28-31, 34, 37 and 38 are rejected and claims 5, 7 and 36 are objected in this Office Action.
I. Priority
The instant application is a 371 of PCT/US2022/036403, filed on July 7, 2022 and claims benefit of US Provisional Application 63/219,459, filed on July 8, 2021.
II. Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 17, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
III. Rejections
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, 2, 4, 8, 10, 12, 17, 20, 22, 24, 28-31, 34 and 37 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pub Chem ID 99606445. The instant invention claims
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The Pub Chem ID 99606445 reference teaches the compound
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(See page 2) wherein R1 is hydrogen; X is NH; m is 0; X1 is CH; R2 is F; R3 is phenyl; q is 2. This species of compound anticipates the genus compound of the instant invention, wherein the genus structure and its definitions are stated above.
Claims 1, 2, 4, 8, 10, 12, 17, 20, 22, 24, 28-31, 34 and 37 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pub Chem ID 38708560. The instant invention claims
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The Pub Chem ID 99606445 reference teaches the compound
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(See page 2) wherein R1 is hydrogen; X is NH; m is 0; X1 is CH; R3 is heterocyclyl; q is 0. This species of compound anticipates the genus compound of the instant invention, wherein the genus structure and its definitions are stated above.
Claims 1, 2, 4, 8, 10, 12, 17, 20, 22, 24, 28-31, 34 and 37 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pub Chem ID 46427754. The instant invention claims
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The Pub Chem ID 46427754 reference teaches the compound
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(See page 2) wherein R1 is hydrogen; X is NH; m is 0; X1 is CH; R3 is heteroaryl; q is 0. This species of compound anticipates the genus compound of the instant invention, wherein the genus structure and its definitions are stated above.
Claims 1, 2, 4, 8, 10, 12, 17, 20, 22, 24, 28-31, 34 and 37 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pub Chem ID 32058953. The instant invention claims
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The Pub Chem ID 32058953 reference teaches the compound
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(See page 2) wherein R1 is hydrogen; X is NH; m is 0; X1 is CH; R3 is heteroaryl; q is 0. This species of compound anticipates the genus compound of the instant invention, wherein the genus structure and its definitions are stated above.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 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.
Claim 38 is 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 treating a condition responsive to kinase inhibition does not reasonably provide enablement for a method for treating a condition responsive to kinase activation. 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.
As stated in the MPEP 2164.01 (a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
1. the nature of the invention,
2. the state of the prior art,
3. the predictability or lack thereof in the art,
4. the amount of direction or guidance present,
5. the presence or absence of working examples,
6. the breadth of the claims,
7. the quantity of experimentation needed, and
8. the level of the skill in the art.
In the instant case
The nature of the invention
The nature of the invention is a method of treating a condition responsive to kinase inhibition. Support for the intended use is found in the in vitro data for Kinase panel showing the inhibitory activity of at least 300 kinases on pages 154-158.
The state of the prior art
The state of the prior art is that the pharmacological art involves screening in vitro and in vivo to determine which compounds exhibit the desired pharmacological activities (i.e. what compounds can treat which specific disease by what mechanism). There is no absolute predictability even in view of the seemingly high level of skill in the art. The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any therapeutic regimen on its face.
The instant claimed invention is highly unpredictable as discussed below:
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. In the instant case, the instant claimed invention is highly unpredictable since Applicants are claiming that the claimed compounds can inhibit all types of protein kinases.
Applicants have tested the instant compounds against a panel of at least 300 kinases in tables 1-4.
Applicants claim is drawn to “kinase modulation” but have only provided support for kinase inhibition and not kinase activation. Applicants specification does not provide enablement for the full scope of a method of treating a condition responsive to kinase modulation as seen in instant claim 38.
For example, Applicants' claims are drawn to a method of treating a condition responsive to kinase modulation. It is the state of the prior art that protein kinases, also known as phosphotransferases, catalyze the transfer of the γ-phosphate from a purine nucleotide triphosphate (ATP and GTP) to the hydroxyl groups of their protein substrates by generating phosphate monoesters using protein alcohol groups as phosphate acceptors. The human genome contains more than 518 protein kinases. The protein kinases can be classified by the amino acid substrate preference: serine-threonine kinases, tyrosine kinases and dual kinases. Since there are more than 518 protein kinases known, the term "kinase" is considered broad and embraces vast subject matter that is not supported by Applicants' specification.
(See Castelo-Soccio, et al. Nature Reviews Immunology, Volume 23,December 2023, 787-806)
The amount of direction present and the presence or absence of working examples
The only direction or guidance present in the instant specification is minimal for a method of treating a condition responsive to kinase modulation. There are no working examples present for activating any kinases. Applicants have only provided data for the inhibition of various kinases.
Test assays and procedure are provided in the specification for a in vitro Kinase panel showing the inhibitory activity of at least 300 kinases on pages 154-158. Receptor activity is generally unpredictable and the data provided is insufficient for one of ordinary skill in the art in order to extrapolate to the other compounds of the claims. It is inconceivable as to which of the claimed compounds can activate protein kinases that would actually be used to treat a disease responsive to kinase activation.
Applicants have not provided any competent evidence or disclosed tests that are highly predictive for the pharmaceutical use of the instant compounds. 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).
The breadth of the claims
The breadth of the claims is drawn to a method for treating a condition responsive to kinase modulation.
The quantity of experimentation needed
The quantity of experimentation needed is undue experimentation. One of skill in the art would need to determine which claimed compounds would activate which type of kinase and could actually be used to treat a kinase dependent disease.
The level of the skill in the art
The level of skill in the art is high. However, due to the unpredictability in the pharmaceutical art, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro or in vivo screening to determine which compounds exhibit the desired pharmacological activity. The specification fails to provide sufficient support of the broad use of the claimed compounds of the invention as modulators of any protein kinase. As a result necessitating one of skill to perform an exhaustive search for which protein kinases can be inhibited or activated by what compounds of the invention in order to practice the claimed invention.
Genentech Inc. v. Novo Nordisk A/S (CA FC) 42 USPQ2d 1001, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to test which protein kinases can be modulated by the compound encompassed in the instant claims, with no assurance of success.
This rejection can be overcome, for example, by amending claim 38 so that the limitation “kinase modulation” now reads “kinase inhibition”.
IV. Objections
Dependent Claim Objections
Dependent Claims 5, 7 and 36 are also objected to as being dependent upon a rejected based claim. To overcome this objection, Applicant should rewrite said claims in an independent form and include the limitations of the base claim and any intervening claim.
V. Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Shawquia Jackson whose telephone number is 571-272-9043. The examiner can normally be reached on 7:00 AM-3:30PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Adam Milligan can be reached on 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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/SHAWQUIA JACKSON/ Primary Examiner, Art Unit 1626