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 reply to the Restriction Requirement, dated June 10, 2026, has been received. By way of this submission, Applicant has elected, without traverse, the species of administering a KRASG12C inhibitor, MRTX1257 as the species of the elected KRAS G12C inhibitor, G12C as a species of KRAS mutation, and lung cancer as a species of cancer.
Claims 1-4 and 6-21 are pending in the application. Claims 4, 6-10, and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on June 10, 2026.
Claims 1-3, 11-19, and 21 are therefore under examination before the Office.
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.
Claims 1-3, 11-14, 17-19, and 21 are 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 RGS3, does not reasonably provide enablement for the genus of all regulators of G-protein signaling. 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.
The claims require detecting mRNA or polypeptide expression levels and/or activity of one or more regulators of G-protein signaling in a biological sample obtained from a cancer patient; and administering to the cancer patient an effective amount of a KRAS G12C inhibitor when expression levels and/or activity of the one or more regulators of G-protein signaling are comparable to a control sample obtained from a healthy subject or a predetermined threshold. According to Li (Science. 2021 Oct 8;374(6564):197-201), the family of regulators of G-protein signaling (RGS) has 20 members, as well as several alternatively spliced variants (page 2 right column, second paragraph). Li also teaches that RGS3 interacts with mutant KRAS G12C; however, Li does not teach which other members of the genus of RGS interact with KRAS. The experiments described in Applicant's specification also only refer to RGS3, two isoforms (p25 and p75), and RGS4.
Pharmaceutical therapies in the absence of in vivo clinical data are unpredictable for the following reasons; (1) the therapeutic may be inactivated before producing an effect, i.e. such as degradation, immunological inactivation or due to an inherently short half-life of the protein; (2) the therapeutic may not reach the target area because, i.e. the therapeutic may not be able to cross the mucosa or the therapeutic may be adsorbed by fluids, cells and tissues where the protein has no effect; and (3) other functional properties, known or unknown, may make the therapeutic unsuitable for in vivo therapeutic use, i.e. such as adverse side effects prohibitive to the use of such treatment. See page 1338, footnote 7 of Ex parte Aggarwal, 23 USPQ2d 1334 (PTO Bd. Pat App. & Inter. 1992). KRAS G12C inhibitors in particular were known to be unpredictable, as Li teaches that only a third of patients with lung cancer respond to these inhibitors (see page 1 of Li and para. 0006 of the instant specification).
The genus of possible RGS that can be used within the scope of the claims is large, yet Applicant merely provides data that only a few members of this genus have the ability to indicate responsiveness to treatment with a KRAS G12C inhibitor. There is nothing in the specification which offers guidance as to which members of the RGS family would be able to perform the claimed method, aside from RGS3 and the two tested isoforms.
Given the unpredictability of the art, the breadth of the genus, and the lack of guidance provided for the entire scope of the genus, undue experimentation would be required to practice the claimed method with a reasonable expectation of success across the entire genus.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary, the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
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, 11-19, 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 claims recite that an effective amount of a KRASG12C inhibitor is administered when expression levels and/or activity of the one or more regulators of G-protein signaling are comparable to a control sample obtained from a healthy subject or a predetermined threshold. The term "comparable" is subjective. Ex parte Anderson, 21 USPQ2d 1241 (Bd. Pat. App. & Inter. 1991). The specification does not give a definition of what is to be considered "comparable", not does the specification describe any objective standard for measuring the scope of the term. Claim scope cannot depend solely on the unrestrained, subjective opinion of a particular individual purported to be practicing the invention. Datamize LLC v. Plumtree Software, Inc., 417 F.3d 1342, 1350, 75 USPQ2d 1801, 1807 (Fed. Cir. 2005). MPEP 2173.05(b)(IV). Without such a definition, the claim is indefinite.
Claims 1-3, 11-19, 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 claims recite a "predetermined threshold". It is unclear what this predetermined threshold is, as the term is never defined by the specification. Without a definition of what the predetermined threshold is or should be, the metes and bounds of the claim become unclear, as one of ordinary skill cannot be appraised of what the "predetermined threshold" is or should be.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 3, 11-19, and 21 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The claims recite a natural phenomenon, a correlation between biomarker levels and lung cancer. This judicial exception is not integrated into a practical application because the claimed data gathering steps do not add a meaningful limitation to the method as they are insignificant extra-solution activity. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because quantifying levels of a biomarker is a well-understood, routine, conventional activity in laboratory technique, and therefore insufficient to amount to an inventive concept.
The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., No. 10-1150 (March 20, 2012). "Laws of nature, natural phenomena, and abstract ideas" are not patentable. Diamond v. Diehr, 450 U.S. 175, 185 (1981); see also Bilski v. Kappos, 561 U.S. 593,604, 95 USPQ2d 1001, 1007 (2010). “Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972). The Supreme Court does acknowledge that it is possible to transform an unpatentable law of nature, but one must do more than simply state the law of nature while adding the words "apply it." Essentially, appending conventional steps, specified at a high level of generality, to laws of nature, natural phenomena, and abstract ideas cannot make those laws, phenomena, and ideas patent-eligible.
In Prometheus, the Court found that "[i]f a law of nature is not patentable, the neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Additionally, "conventional or obvious [pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law". Flook, 437 U.S., at 590; see also Bilski, 561 U. S.: "[T]he prohibition against patenting abstract ideas 'cannot be circumvented by'. . . adding 'insignificant post-solution activity'" (quoting Diehr, at 191-192).
The Court also summarized their holding by stating "[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately."
The first step under this guidance is determining if the claim is directed to one of the four statutory categories (process, machine, manufacture, or composition of matter). In this case, the claims are a method (process). The second step is determining if the claims recite or involve judicial exception(s), such as laws of nature, natural phenomena, natural products, or an abstract idea. In this case, the claims are drawn to "method[s] for selecting a cancer patient". The claims recite a natural correlation/observation of a natural phenomenon, the relationship between suitability for treatment with a KRAS G12C inhibitor and expression levels and/or activity of one or more regulators of G-protein signaling in a biological sample obtained from the patient, which is a judicial exception. Furthermore, the judicial exception is not integrated into a practical application, as the claims do not rely on or use the exception in a further step. See MPEP 2106.04(d). Thus, it must be determined if the claim as a whole recites something significantly more than the judicial exception.
Claim 1 requires two steps: a detection of expression levels and/or activity of regulators of G-protein signaling step, and an administering step.
For the first step, the use of assays to determine levels of a biomarker has been characterized by the Court as “mere data gathering” and “insignificant extra-solution activity”. Determining the level of a biomarker in blood by any means has been recognized by the courts as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity. Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017). MPEP 2106.05 (II). Claims 17 and 18 recite several well-known methods to determine expression levels of mRNA or polypeptides. The determining step cannot be said to add significantly more to the claim.
The second step of the claim requires administering a KRAS G12C inhibitor if expression levels and/or activity of one or more regulators of G-protein signaling are comparable to a control sample or a predetermined threshold. Inversely, if the expression levels and/or activity are not comparable to the control sample or a predetermined threshold, then the administering step is not performed. For patients who do not meet the criteria of comparable levels of protein expression and/or activity, the only step required is the first step. For these patients, there is nothing in the step that adds significantly more to the judicial exception.
The remaining claims further characterize the exception itself, e.g., additional details for the choice of inhibitor or the specific KRAS mutation, or how the determining step is to be performed. These specifics also do not add significantly more, for the above reasons.
Therefore, claims 1, 3, 11-19, and 21 are patent ineligible.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Lipford (US20200222407A1, cited in IDS as WO2020106647A2) teaches a method of treating lung cancer, comprising administering a KRASG12C inhibitor (para. 0009 and 0017). Lipford further teaches that the lung cancer may have a G12C mutation (para. 0024). However, Lipford does not teach detecting mRNA or polypeptide expression levels and/or activity of one or more regulators of G-protein signaling in a biological sample obtained from the cancer patient.
Hilf (WO2020236940A1) teaches a method of treating non-small cell lung cancer by administering an inhibitor of KRAS G12C (page 57, line 32 through page 58, line 5). Hilf further teaches that the KRAS G12C inhibitor MRTX1257 is known to be potent and selective, and have desirable efficacy in xenograft models of cancer (page 59, lines 5-9).
No claim is allowed.
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/PETER JOHANSEN/Examiner, Art Unit 1644
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