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 .
Election/Restrictions
Applicant’s election without traverse of an SOS1 inhibitor BI-3406, MEK inhibitor trametininb, and KRAS 12C inhibitor sotosarib in the reply filed on 2026 May 13 is acknowledged. In the interest of compact prosecution, a search of an SOS 1 inhibitor has been extended to compounds of claim 4 and MEK inhibitors of the following scope:
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Variable Q is any heteroatom.
A search of the KRAS G12C inhibitor has not been limited.
Claim 15, 17, and 18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 2026 May 13.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2023 October 6 was submitted in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
Claim(s) 1-3 and 6-8 is/are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph due to lack of written description.
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 by him.
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 species is sufficient.” 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, claims 1-3 and 6-8 are drawn to a method of treating and/or treating preventing cancer with an SOS1 inhibitor, a MEK inhibitor, or a combination of an SOS 1 inhibitor and a MEK inhibitor in which the cancer is resistant to a KRAS G12C inhibitor.
(1) Level of skill and knowledge in the art:
AKINLEYE (Journal of Hematology and Oncology, 2013, 6:27, 1-11) describes MEK inhibitors (page 5 of 11, table 1 and figure 3).
EVELYN (Chemistry and Biology, 2014, 21, 1618-1628) describes SOS1 inhibitors (page 1623).
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KIM(Cell, 2020, 183, 850-859) describes various KRAS-G12C inhibitors (page 852, figure 1A, shown below). Are these KRAS-G!2C inhibitors intended as the treatment of a cancer.
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(2) Partial structure:
Claim 4 and 5 define specific SOS1 inhibitors and MEK inhibitors specifically.
(3) Physical and/or chemical properties and (4) Functional characteristics:
Compounds of claims 4 and 5 have aromatic heterocyclic fused ring systems.
The MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that claim(s) 1-3 and 6-8 is/are broad and generic, with respect to all possible compounds encompassed by the claims. The possible structural variations are limitless to any method of treating cancer with an SOS1 inhibitor, MEK inhibitor, or a combination thereof. Although the claims may recite some functional characteristics, the claims lack written description because there is no disclosure of a correlation between function and structure of the compounds beyond those compounds specifically disclosed in the examples in the specification. Moreover, the specification lack sufficient variety of species to reflect this variance in the genus. While having written description of compounds identified in the specification tables and/or examples, the specification does not provide sufficient descriptive support for the myriad of compounds embraced by the claims.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Claims 1-8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification is enabling for treatment of pancreatic cancer, non-small cell lung cancer, and colorectal cancer and non-enabling for the treatment of the scope of cancers recited nor the prevention of the scope cancers recited. 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/or use the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’” (Wands, 8 USPQ2sd 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” (Wands, 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
Consideration of the relevant factors sufficient to establish a prima facie case for lack of enablement is set forth herein below:
The nature of the invention and (2) the breadth of the claims:
The claims are drawn to treating and/or preventing a KRAS G12C cancer with a Son of sevenless 1 (also known as SOS1) inhibitor, a mitogen-activated protein kinase kinase (also known as MEK) inhibitor, or a combination of an SOS1 inhibitor and MEK inhibitor. Thus, the claims taken together with the specification imply a KRAS G12C cancer can be treated or prevented with an SOS1 inhibitor, a MEK inhibitor, or a combination of SOS1 inhibitor and MEK inhibitor.
The state of the prior art and (4) the predictability or unpredictability of the art:
ELEZ (Cancer Cell, 2020, 38, 785-787, cited in the IDS) describes the following ideas: KRAS G12C is present lung non-small cell lung cancer, colorectal cancer, and pancreatic cancer (page 785, column 1, last paragraph to page 786, column 2); and more research is needed to understand what cancers are related to KRAS G12C (abstract; page 787, column 1, last paragraph to column 2 first paragraph).
HERBST (Nature, 2018, 553, 446-454) describes that more research is needed to understand how to prevent non-small cell lung cancer (page 452, “future perspectives” section).
The relative skill of those in the art:
While the artisan generally would have an advanced degree in the relationship of KRAS G12C to cancers, their high level of skill and knowledge is insufficient to overcome the lack of understanding as to how in the relationship of KRAS G12C to cancers or to overcome the art recognition that this disease is poorly understood and treatments have generally failed.
The amount of direction or guidance presented and the presence or absence of working examples:
The specification has provided guidance for treatment of pancreatic cancer, non-small cell lung cancer, and colorectal cancer.
The specification does not provide guidance for the treatment of the scope of cancers recited nor the prevention of the scope cancers recited.
The quantity of experimentation necessary:
Considering the state of the art as discussed by the references above, particularly with regards to the specific cancers related to KRAS G12C and the high unpredictability in the art as evidenced therein, and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of the claims.
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 1-3 and 6-8 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.
Claims 1-3 and 6-8 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01. The omitted elements are: the structural elements of an SOS1 inhibitor and a MEK inhibitor. None of these claims specify the structural requirements that are used individually or in combination with each other.
AKINLEYE (Journal of Hematology and Oncology, 2013, 6:27, 1-11) describes MEK inhibitors (page 5 of 11, table 1 and figure 3). Are these MEK inhibitors intended to be present in a method of claim 1?
EVELYN (Chemistry and Biology, 2014, 21, 1618-28) describes SOS1 inhibitors (page 1623). Are the compounds shown intended be part of the method recited in claim 1?
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KIM (Cell, 2020, 183, 850-859) describes various KRAS-G12C inhibitors (page 852, figure 1A, shown below). Are these KRAS-G!2C inhibitors intended as the treatment of a cancer.
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Due to the metes and bounds of an SOS1 inhibitor, MEK inhibitor, and KRAS G12C inhibitor not being recited in claim 1, it is difficult to determine the metes and bounds of the method recited.
Claims 3-5 recite limitations for a KRAS G12C inhibitor, SOS1 inhibitor, and a MEK inhibitor respectively. There is insufficient antecedent basis for this limitation in the claim because parent claim 1 does not recite the structural metes and bounds of each of these agents.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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.
Claims 1, 2, and 4-7 rejected under 35 U.S.C. 103(a) as being unpatentable over HOFMANN (Cancer Discovery, 11, 142-157, available 2021 January 6).
Determining the scope and contents of the prior art
HOFMANN describes the following ideas: BI3406 treats pancreatic cancer (page 148, column 2, paragraph 3 to page 149, column 1, paragraph 1); the combination of BI-3406 and trametinib has strong synergistic effects against MIA PaCa-2, a KRAS G12C cancer and colorectal cancer (page 149, column 1, paragraph 2 to page 151, column 2, paragraph 2; page 154, column 2, paragraphs 2 and 3); BI-3406 combination therapy with KRAS G12C inhibitor AMG 510 resulted in prolonged suppression of pERK as compared with AMG 510 monotherapy (page 151, last paragraph to page 151, column 1, paragraph 2); and that combination therapy of BI-3406 with trametinib would be beneficial with KRAS G12C inhibitor AMG 510 (page 152, column 2, paragraphs 2 and 3). BI-3406 combination therapy with KRAS G12C inhibitor AMG 510 resulted in prolonged suppression of pERK as compared with AMG 510 monotherapy (page 151, last paragraph to page 151, column 1, paragraph 2) in NCI-H358 cells.
Ascertaining the differences between the prior art and the claims at issue
Hofmann does not explicitly describe the combined administration of BI-3406 and trametinib with a cancer resistant to treatment with an inhibitor of KRAS G12C.
Resolving the level of ordinary skill in the pertinent art
Those of relative skill in the art are those with level of skill of the authors of the references cited to support the examiner’s position (MD’s, PhD’s, or those with advanced degrees and the requisite experience in preparation of compounds of the elected group).
Considering objective evidence present in the application indicating obviousness or nonobviousness
Hofmann describes the separate ideas that the combined administration of BI-3406 and trametinib has success against pancreatic cancer and colorectal cancer. Even though it is not explicitly described it is suggested that BI 3406 by itself and combination therapy comprising BI 3406 and trametininib is expected to work (page 152, column 2, paragraphs 2 and 3).
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
The Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 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 in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary 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.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Conclusion
Claims 1-8 are not allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NOBLE E JARRELL whose telephone number is (571)272-9077. The examiner can normally be reached 9:00 AM to 5:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Fereydoun Sajjadi can be reached at 571-272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NOBLE E JARRELL/Primary Examiner, Art Unit 1699
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