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 9-24 are pending.
Priority
Applicant’s claim for benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. This application is a national stage entry of and claims priority to PCT/US2022/028711 filed on 5/11/2022 and further claims priority to provisional application number 63/187,768, filed 5/12/2021.
Information Disclosure Statement
All references from IDS(s) received on 11/09/2023 have been considered unless marked with a strikethrough.
Claim Rejections - 35 USC § 112(b)
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.
Claim 10 is 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 term “oxepane isomer” in claim 10 is a relative term which renders the claim indefinite. The term “oxepane isomer” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The Specification does not provide an example of what an oxepane isomer is. This could range from a ring expansion to an oxepane or an oxepane conjugated at any part of the compound. Thus, there are multiple structure interpretations and it is unclear what the structure of such an isomer is based on the claims and specification.
Claims 13 and 21 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 term “associated with” in claims 13 and 21 is a relative term which renders the claim indefinite. The term “associated with” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The Specification does not provide an example of what range of possibilities “associated with” can include. For example, a RAS mutation can be in a cancer cell line, as represented by the Specification, or a congenital syndrome, such as a heart defect, which is not represented in the Specification. Furthermore, would a SHP2 mutation be associated to a RAS mutation because it is also a mutation such that they are associated by both being a mutation. Thus, there are multiple interpretations and it is unclear what the diseases and disorders would be “associated with” either cells having a SHP2 mutation (Claim 13) or “associated with” “a RAS protein mutation” (Claim 21) based on the claims and specification.
Claim Rejections - 35 USC § 112(a)
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 9 and 15-17 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 claim(s) contains 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. See MPEP 2163.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The courts have stated that, “To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “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, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated that, “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...”) Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed genus is sufficient. See MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
In the instant case, the claims of the present invention embrace compounds of Formula I, including any “prodrugs”, thereof.
The specification fails to
Show possession of the full scope of what constitutes as a prodrug in the context of the invention
Fails to establish a structure/function correlation for these terms, or provide a representative number of examples to establish possession of the structural space that would entail the BRI of prodrugs or their compound structures, as they have not provided any examples of either.
Status of the prior art/Lack of structure function correlation/Lack of representative number of examples
The art teaches that prodrugs may have their own pharmacological activity. Zhang et al. (Acta Pharmaceutica Sinica B 2018; 8(5):72-732) teaches that prodrugs of a drug can be completely new drug candidates away from the parent drug, therefore emphasizing the importance of designing prodrugs in a manner that requires the causes that necessitate the use of the prodrug approach be defined and clearly understood. Without definitive boundaries the Examiner can only assume a prodrug can be as broad as using a macromolecular moiety.
One of ordinary skill would not expect these compounds to necessarily have similar properties and a person skilled in the art would not be able to determine whether the structure or function of the claimed invention would be maintained. Specifically, in view of the teachings of Zhang, if small structural changes to compounds within the field of the invention cause a change in the order of magnitude, a person skilled in the art could not predict what would be expected of large structural changes. In the absence of a disclosed structure, there can be no correlation between the function and structure of the claimed “prodrug” in the instant application.
With respect to the representative numbers of examples, the specifications has over 400 specific structural examples for the core compound presented in the instant claims but lacks any representative examples of structures of prodrugs. Therefore, the specification has failed to provide a representative number of examples to establish possession of the structural space that would entail the BRI of prodrugs or their compound structures, as they have not provided any examples of either.
This rejection would be overcome by amending the claims to remove the term “prodrug.” The dependent claims allow for prodrugs of the compounds in the claims to be within the scope of the claim.
Claim Rejections - 35 USC § 112(a)
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 9, 13, and 21 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 claim(s) contains 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. See MPEP 2163.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The courts have stated that, “To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “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, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated that, “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...”) Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed genus is sufficient. See MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
In the instant case, the claims of the present invention embrace a method of treating a subject having a “disease or disorder” (Claim 9) including a “RAS protein-related disease or disorder” (Claim 21).
The specification fails to
Show possession of the full scope of what constitutes as a “disease or disorder” in the context of the invention or define what “protein-related” could mean.
Fails to establish a structure/function correlation for these terms, or provide a representative number of examples to establish possession of the functional space that would entail the BRI of disease/disorder.
Status of the prior art/Lack of structure function correlation/Lack of representative number of examples
The art teaches that SOS inhibitors can be used for a range of different diseases. Hillig et al. (Proc. Natl. Acad. Sci. U.S.A. 116 (7) 2551-2560, https://doi.org/10.1073/pnas.1812963116 (2019).) teaches that SOS1 inhibitors block RAS activation in various types of cancer. Suire at al. (Journal of Leukocyte Biology, Volume 106, Issue 4, Oct 2019, Pages 815–822) teaches that SOS1 signaling plays a key role in neutrophil proinflammatory responses, which would broaden the possibilities for disease targets outside of just cancer. Without definitive boundaries the Examiner can only assume a disease or disorder can be as broad as any disease or disorder involving neutrophil proinflammatory responses.
One of ordinary skill would not expect these compounds to have similar properties and a person skilled in the art would not be able to determine whether the structure or function of the claimed invention would be maintained. Specifically, in view of the teachings of Hillig and Suire, the compounds can be used in any type of disease or disorder and a person skilled in the art could not predict what would be expected of the target possibilities of the compound.
With respect to the representative numbers of examples, the specifications has over 40 specific disease examples in the realm of cancer but lacks any representative examples of diseases or disorders outside of those related to cancer, much less which diseases are “associated with a RAS protein mutation”. Therefore, the specification has failed to provide a representative number of examples to establish possession of the functional space that would entail the BRI of diseases or disorders.
This rejection would be overcome by amending the claims to more explicitly define “diseases or disorders” in the context of the invention. The Examiner encourages the Applicant to schedule an interview if anything is unclear.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 9-12, and 20-24 are rejected under 35 U.S.C. 103 as being unpatentable over Lee, G. et al. (WO2022217053A1; claims priority to U.S. provisional Application Ser. No.63/172,786, filed April 9, 2021; “Lee”) in view of Pitzen, J. et al. (WO2019212990A1; cited in IDS filed 11/09/2023; “Pitzen”).
Note that this 103 is relevant to the scope of the claims that the Applicant was in possession of, refer to 112 rejection.
Lee teaches an overlapping genus structure with compound in step a of Claim 1 (Claim 1) as an SOS1 inhibitor for treating a subject having a RAS protein-related disease or disorder, including ovarian cancer (para. 0143), as required by instant claims 9 and 11. More specially, Lee teaches a structural example of the compound in claim 1 (End of Claim 1, aka RMC-0331).
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(Lee, Claim 1).
Lee teaches the method for use in RAS-protein related disease or disorder, including RAS protein mutations, such as G12 K-ras mutations (para 0261), as required by instant claims 20-24.
Lee also teaches the compound can be administered with an mTOR inhibitor (Pg. 1016, para. 0699). Lee fails to teach the co-administration with the mTOR inhibitor in (b) of instant claim 1.
However, Pitzen teaches the mTOR compound of instant claim 1 (Claim72, Example 12), as required by claims 9-10.
It would be obvious to a person skilled in the art at the time to substitute the mTOR compounds taught by Lee for another mTOR compound, such as the one taught by Pitzen to arrive at the instant invention.
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down inGraham.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement
to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a
reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same
field or a different one based on design incentives or other market forces if the variations are
predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of
ordinary skill to modify the prior art reference or to combine prior art reference teachings to
arrive at the claimed invention.
Applying KSR example rationale (B), it would have been prima facie obvious to extract the method of treating a subject or disorder with an SOS-1 inhibitor in combination with an mTOR inhibitor, as taught by Lee, and substitute the mTOR inhibitor for another known compound, such as RMC-5552, as taught by Pitzen. Therefore, claims 9-12 and 20-24 would have been obvious to a person skilled in the art at the time.
Claims 9-24 are rejected under 35 U.S.C. 103 as being unpatentable over Lee, G. et al. (WO2022217053A1; claims priority to U.S. provisional Application Ser. No.63/172,786, filed April 9, 2021; “Lee”) in view of Pitzen, J. et al. (WO2019212990A1; “Pitzen”) in further view of LaRochelle (Nat Commun. 2018 Oct 30;9(1):4508; “LaRochelle”)
Claims 9-12, and 20-24 are taught by the combined teachings of Lee and Pitzen and are incorporated herein.
With respect to claims 13-19, Lee teaches a method of treating a subject having a disease or disorder characterized by SHP2-mediated activation of a RAS protein comprising administering to a subject in need of such treatment a therapeutically effective amount of a SOS1 inhibitor (para. 0243) and stimulation by cytokines or growth factors acting through RTKs leads to exposure of the catalytic site resulting in enzymatic activation of SHP2, as required by instant claim 14 (para. 0117). Lee also teaches treating with a SHP2 inhibitor.
Lee fails to explicitly teach using the compound to treat a disease with a SHP2 mutation or where the SHP2 mutation is expressed after prior treatment with a SHP2 inhibitor, as required by instant claims 13 and 15-17.
However, LaRochelle teaches strongly activating mutations of SHP2 confer resistance to allosteric inhibition and the primary challenge with orthosteric inhibitors is to achieve sufficient selectivity for SHP2 over other cellular phosphatases, which may be further thwarted by the SHP2 cancer mutations that localize to residues near the active site, such as S502, G503, and Q510 (Discussion, Para. 4).
Since Lee teaches treatment may occur after treatment with SHP2 inhibitors and LaRochelle teaches that treatment with SHP2 inhibitors confers mutation, it would be obvious to a person skilled in the art that the subject may have a SHP2 mutation, including G305, after prior treatment with a SHP2 inhibitor, as required by instant claims 13-19. Furthermore, because SHP2 is upstream of SOS1/2 on the signaling pathway, it would be obvious to a person skilled in the art to approach a subject with a SHP2 mutation with an SOS1/2 inhibitor, as taught by Lee (Figure 1).
Applying KSR example rationale (G), it would have been prima facie obvious to extract the method of treating a subject or disorder with an SOS-1 inhibitor in combination with an mTOR inhibitor, as taught by Lee and Pitzen, and treat a subject containing an SHP2 mutation. A person skilled in the art would have been motivated to do so because it is known that treatment SHP inhibitors confer SHP mutations, as taught by LaRochelle. Furthermore, because SHP2 is upstream of SOS1/2 on the signaling pathway, as taught by Lee, it would be obvious to a person skilled in the art to approach a subject with a SHP2 mutation with an SOS1/2 inhibitor. Therefore, claims 9-24 would have been obvious to a person skilled in the art at the time.
Conclusion
Claims 9-24 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NICOLA MARIA BAUER whose telephone number is (703)756-1269. The examiner can normally be reached Monday-Friday 7:30-5 EST.
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, Clint Brooks can be reached at (571) 270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/N.M.B./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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