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
STATUS OF THE CLAIMS: Claims 1-24 are pending in this application.
Claim Rejections - 35 USC § 112, 2nd paragraph
The following is a quotation of the second paragraph of 35 U.S.C. 112:
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.
Claim 21 is rejected under 35 U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 21 refers to compounds “selected from Table 2” and this render the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Applicant is reminded that a claim should be complete by itself. This claim is deemed to be incomplete because it incorporates reference to compounds or a table in the specification. Examiner suggests adding the compound(s) to the claim (structure or name). Correction is required.
Claim Rejections - 35 USC § 112, 1st paragraph
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 1-24 (including claims dependent thereon are claims that relate back to independent or dependent claims) 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 1 and 22-24 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for specific compounds disclosed in the specification, does not reasonably provide enablement for prodrugs, tautomers, and isotopologues of those compounds and composition containing same. 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 and use the invention commensurate in scope with these claims.
Claims 1 and 22-24 are rejected because the claims recite specific compounds and prodrugs, tautomers, and isotopologues of said compounds. However, the specification fails to teach the preparation or identity of prodrugs, tautomers, and isotopologues. Therefore, the specification is not adequately enabled for making and/or using prodrugs, tautomers, and isotopologues.
Identifying an ester requires knowledge of in vivo regeneration pathways of instant compounds and short of extensive experimentation, would be the skilled artisan would need much more data to determine prodrugs and solvates of the instant compounds and compositions.
Applicants have not provided any clear guidance that would provide prodrugs, tautomers, and isotopologues of the instant compounds that will regenerate in vivo to the instant compounds by one or more biological processes or methods for preparing prodrug and solvates and solvates s. It is not the norm that one can predict with any accuracy whether a particular ester form of an active compound will be more soluble, more easily handled in formulations or more bioavailable without art recognized data to support same. The specification provides no guidance as to what type(s) of prodrugs and solvates are suitable for the instant compounds. Generally, prodrugs, tautomers, and isotopologues themselves are not considered to be therapeutically active but only to provide the active compound in vivo.
For rejections under 35 U.S.C. 112, first paragraph, the following factors must be considered (In re Wands, 8 USPQ2d 1400, 1404 (CAFC, 1988)):
1) Nature of invention.
2) State of prior art.
3) Quantity of experimentation needed
4) Level of predictability in the art.
5) Amount of direction and guidance provided by the inventor.
6) Existence of working examples.
7) Breadth of claims.
8) Level of ordinary skill in the art.
Nature of the invention
The nature of the invention is the preparation of compounds and compositions under the genus of a structural Formula (I). As stated, however prodrugs, tautomers, and isotopologues are also intended. The nature of prodrugs, tautomers, and isotopologues is not set forth nor is the manner in which the prodrugs, tautomers, and isotopologues are to be prepared or the core compounds modified prodrugs, tautomers, and isotopologues.
State of the prior art
The state of the prior art is that acceptable salts are known in the pharmaceutical industry. Prodrugs, tautomers, and isotopologues in related compounds are not modified.
Quantity of experimentation needed
The quantity of experimentation needed is undue. The skilled artisan would need to regenerate in vivo the instant compounds by one or more biological processes. All of which require undue experimentation. Applicant has not postulated a metabolic pathway or mechanism, which facilitate conversion of the prodrugs, tautomers, and isotopologues into an active agent.
Level of predictability in the art
The art pertaining to the preparation and use of esters is high as prodrugs, tautomers, and isotopologues are compound specific and not all prodrugs, tautomers, and isotopologues have the ability to regenerate in vivo. (See Wolff, M.E., “Burger’s Medicinal Chemistry”, pp. 975-977, and Banker et al., “Modern Pharmaceuticals”, p. 596).
Amount of direction and guidance provided by the inventor
There is no guidance provided as all the examples in the specification are drawn to the preparation of compounds disclosed in the specification and not to prodrugs, tautomers, and isotopologues. The lack of guidance to prepare any esters is not provided by the inventor.
Existence of working examples
As discussed above, working examples are drawn to the preparation of compounds disclosed in the specification and not to prodrugs, tautomers, and isotopologues. The lack of guidance to prepare any prodrugs, tautomers, and isotopologues is telling. There is no direction or guidance provided by Applicant to prepare prodrugs, tautomers, and isotopologues of the instant invention.
Breadth of claims
The breath of the recited compounds and compositions in the claims includes prodrugs, tautomers, and isotopologues for which there have been provided no specific examples or procedural steps to prepare prodrugs, tautomers, and isotopologues. Failure to teach how to make the instant compounds makes teaching how to use the compounds unduly difficult, if not impossible.
Level of ordinary skill in the art
The level of ordinary skill in the art is high due to the unpredictability in the chemical art.
Hence, as discussed above, to practice the claimed invention herein, a person of ordinary skill in the art would have to engage in undue experimentation to test which prodrugs, tautomers, and isotopologues can be used in the instant claim, with no assurance of success. Therefore, applicant must show that the specification teaches the preparation of prodrugs, tautomers, and isotopologues or limit the claims accordingly.
Claim 24 is 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.
Claim 24 is rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for “treating” or “treatment”, does not reasonably provide enablement for “preventing” or “prevention”. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. Applicant is entitled to treatment or treating, not “prevention”.
The determination that “undue experimentation” would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations. In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404.
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”. These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The breadth of the claims
The breadth of the instant claims is seen to encompass methods for preventing cancer by administering to a patient in need of such treatment a therapeutically effective amount of the compound of Formula (I). Applicant failed to exactly define how to prevent these diseases. Additionally, it is clear that Applicant has not limited his definition of prevention to one particular disease. Thus, claim is extremely broad.
The nature of the invention
Currently, there are no known agents with the therapeutic efficacy to prevent cancers. The art does not disclose an active agent or combination of active agents, which is recognized as prevention for the conditions cited supra. The prior art does not teach or disclose a treatment modality wherein healthy subjects are treated with an active agent or agents and there is no evidence that none of the associated symptoms or disease state characteristics are ever manifested. The disclosure does not direct the skilled artisan to an art, which satisfies the requirement for preventing a disease state associated with these disorders.
The level of predictability in the art
Since the art does not disclose any therapeutic preventative agents, the skilled artisan would not predict, in the absence of proof to the contrary, that the active agent(s) instantly claimed are efficacious in preventing the conditions as broadly claimed. The assertion of a broad application, as set forth in the instant method claims, necessarily requires evidence to support Applicant’s asserted methods. The Examiner notes there are no known agents recognized as preventative agents, and one of skill in this art could not predict, from the evidence of record, that the active agents asserted to be useful in the instantly claimed method, can indeed prevent these disorders.
The amount of direction provided by the inventor
The Examiner notes, there is not seen sufficient guidance provided in the form of administration profiles, combination ratios of the active agents or reference to same in the prior art to provide the skilled artisan with sufficient guidance to practice the instant preventative method. Prevention is seen to encompass administering the active agent to a subject in need and noting the fact that symptoms of conditions such as these disorders never manifest themselves. The data and evidence provided in the instant disclosure leads the examiner to doubt the objective truth of assertions of prevention of any of the conditions.
The existence of working examples
There is not seen in the disclosure, sufficient evidence to support Applicant’s claims of prevention. There is not seen sufficient working examples or data from references of the prior art providing a nexus between that which applicant asserts as proof of a method for preventing these disorders from the data and evidence currently provided on the record to support methods drawn to preventing any condition.
The level of one of ordinary skill
The ordinary skill artisan would not be able to practice the claimed invention of preventing these disorders with the current disclosure.
The quantity of experimentation
A great deal of experimentation is required. In lieu of the fact that no animal models exists which can reasonably suggest successful prevention of these disorders, it may be necessary for an ordinary skilled artisan to have clinical data in order to practice the claimed invention.
Thus, it can be safely concluded that the instant case fails to provide an enabling disclosure for the prevention of cancer.
Claim 24 is 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 claims contain 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.
Claim 24 is directed to a method of treating cancer. The term cancer is interpreted to include any and all forms of cancer. In light of this, it can be asserted that in spite of the vast expenditure of human and capital resources in recent years, no one drug has been found which is effective in treating all types of cancer because it is not a simple disease, nor is it even a single disease, but a complex of a multitude of different entities, each behaving in a different way. In re Hozumi, 226 USPQ 353 (ComrPats 1985).
The determination that “undue experimentation” would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations. In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404.
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”. These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The breadth of the claims
The breadth of the instant claims is seen to encompass methods for treating cancer by administering to a patient in need of such treatment a therapeutically effective amount of compound of Formula (I). Thus, the claims are extremely broad.
The nature of the invention
The nature of the invention is the treatment of cancer through the use of the claimed compound and derivatives thereof. Currently, there are no known agents that treat cancers all inclusively. (See Pinedo et al. pages 1-2).
The level of predictability in the art
The treatment of cancer is highly unpredictable due to the differing forms of cancerous cells, their location, their potential for metastases, the fact that cancer therapeutics is palliative rather than curative and that cancer treatment readily harms normal tissues. (See McMahon, page 5, col. 2).
The amount of direction provided by the inventor.
The applicant has not demonstrated sufficient guidance provided in the form of administration profiles, combination ratios of the active agents or reference to the same in the prior art to provide a skilled artisan with sufficient guidance to practice the instant treatment of cancer claimed. Further, the applicant discloses that an effective amount of the compound will be administered without providing any direction other than that the compounds of the invention have a high therapeutic index and follows this with a definition readily found in a basic pharmacology textbook. It should be noted that the therapeutic index of a drug in humans is almost never known and is only determined through clinical experience.
The existence of working examples.
There is not seen in the disclosure, sufficient evidence to support Applicant’s claims of treating cancer. 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, 27 USPQ2d 1510 (CAFC). The disclosure does not demonstrate sufficient evidence to support the applicant's claim to the treatment of cancer. There are not sufficient working examples or data from references of the prior art to provide a nexus between those examples and a method of treating cancer with the claimed compound.
The level of one of ordinary skill.
The level of skill is that of one with a doctoral understanding of cancer therapeutics.
The quantity of experimentation.
A great deal of experimentation is required. In order for there to be a method of treating cancer generally, as claimed by the applicant, it would be necessary to show that a vast range of different types of cancers can be treated that have differing cell types, locations and potentials for metastases. Furthermore, direction, in the form of examples, must be shown to determine what an effective dose may be. The references submitted do not demonstrate this. Therefore, one of ordinary skill in the art would require a significant amount of experimentation in order to determine the effective dosage to treat the multitudes of different types of cancer with the claimed compound individually or in combination with other therapeutic agents.
Thus, it can be safely concluded that the instant case fails to provide an enabling disclosure for the treatment of cancer.
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 and 22-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu et al., (WO2022/047260).
Applicant claims compounds of the following Formula (I):
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216
308
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,
wherein all the variables are defined in the claims.
This reference discloses compounds and compositions of formula I in paragraphs [0015]-[0018] and pages 268-299. (See Abstract, Compound 19 and entire document). The compounds and compositions read on the instant claim. Since this reference teaches the exact compounds and compositions, Applicant’s claims are anticipated, and thus, rejected under 35 U.S.C. 102.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 1-24 are rejected under 35 U.S.C. 103 as being obvious a by Liu et al. (WO2022/047260).
Applicant claims compounds of the following Formula (I):
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216
308
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Greyscale
,
wherein all the variables are defined in the claims.
This reference discloses a generic group of heterocyclic compounds, compositions, methods for treating and KRAS inhibitors which embraces Applicants’ claimed compounds, methods for treating, compositions and KRAS inhibitors. The claims differ from the reference by reciting specific species and a more limited genus than the reference. However, it would have been obvious to one having ordinary skill in the art at the time of the invention to select any of the species of the genus taught by the reference, including those instantly claimed, because the skilled chemist would have the reasonable expectation that any of the species of the genus would have similar properties, and thus, the same use as taught for the genus as a whole. One of ordinary skill in the art would have been motivated to select the claimed compounds from the genus in the reference since such compounds would have been suggested by the reference as a whole. A prior art disclosed genus of useful compounds is sufficient to render prima facie obvious a species falling within a genus. Thus, Applicant’s claims are obvious, and therefore, rejected under 35 U.S.C. 103.
Conclusion
Claims 1-24 are pending. Claims 1-24 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL V WARD whose telephone number is (571)272-2909. The examiner can normally be reached M-F 9am to 5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL V WARD/ Primary Examiner, Art Unit 1622
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