DETAILED ACTION
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 group I, claims 1-9 and species: mutation, sequence, nonsense mutation and SMAD4 in the reply filed on 08/21/2025 is acknowledged.
Claims 10-19 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 08/21/2025.
Claims 1-9 are under examination. Claim 1 is under examination with respect to mutation. Claim 2 is under examination with respect to sequence. Claim 8 is under examination with respect to nonsense mutant. Claim 9 is under examination with respect to SMAD4.
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 1-9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more. The claims recite a law of nature and abstract idea. This judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
The following inquiries are used to determine whether a claim is drawn to patent-eligible subject matter.
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? Yes, all of the claims are directed to a process.
Step 2A. Is the claim directed to a law of nature, a natural phenomenon or an abstract idea (judicially recognized exception) and does the claim recite additional elements that integrate the judicial exception into a practical application?
Yes, the claims are directed to law of nature/natural phenomenon. Claim 1 recites at least one marker gene whose mutational status indicates a favorable outcome. The recited relationship is a natural phenomenon that exists apart from any human action. This type of correlation is a consequence of natural processes.
The claims also recite the judicial exception of an abstract idea and particularly mental processes. Claim 1 recites the abstract idea of a mental process. Claim 1 recites a method for determining whether to start or continue a treatment of cancer. Claim 1 recites “determining” to start or continue treatment with the at least one inhibitor if measuring indicates that the tumor cells in the at least one biological sample comprise the at least one marker gene whose mutation status indicates a favorable outcome and the at least one inhibitor is “selected” specifically in view of the determination of the mutational status of the at least marker gene. Neither the specification or the claims set forth limiting definition for determining or selecting and the claims do not set forth how determining is accomplished. The broadest reasonable interpretation of the determining step and whereby select is a step that can be accomplished mentally by evaluating data and critical thinking process wherein one mentally reads information in a database or report regarding mutational status then draws a mental conclusion. Such “determining” encompasses process that may be performed mentally and this is an abstract idea.
Having determined that the claims recite a judicial exception, it is then determined whether the claims recite additional elements that integrate the judicial exception into a practical application.
The claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). For example, the claims do not practically apply the judicial exception by including one or more additional elements that the courts have stated integrate the exception into a practical application:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
An additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
An additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
An additional element effects a transformation or reduction of a particular article to a different state or thing; and
An additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological
environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
As mentioned above, a claim limitation can integrate a judicial exception by applying or using the judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. When evaluating this consideration one must the following:
(i) the particularity or generality of the treatment or prophylaxis limitation;
(ii) whether the limitations have more than a nominal or insignificant relationship to the exception; and
(iii) whether the limitations are merely extra solution activity or field of use.
The steps of “selecting to start or continue” a treatment with at least one inhibitor is not particular i.e., specifically identified so that it does not encompass all applications of the judicial exception. In other words the claims broadly encompass any and all treatments for cancer comprising any all inhibitors. Additionally the treatment limitations do not appear to have a significant relationship to the exception. The recited steps are a judicial exception, particularly an abstract idea. Selecting to start or continue treatment is a mental process in which someone makes a determination of a treatment. The claim does not recite administering any particular treatment to a particular subject. For these reasons the recitation of determining to start or continue treatment does not integrate the judicial exceptions into a practical application.
In addition to the judicial exceptions the claims recite biomarker sequence and nonsense mutation (claim2-4 and 7-8). Claims 5-6 specify a MEK inhibitor and claim 9 specific a marker gene, SMAD4. These additional steps/elements are not considered to integrate the judicial exception into a practical application because they merely add insignificant extra-solution activity (data gathering) to the judicial exception.
Step 2B - Does the claim recite additional elements that amount to significantly more than the judicial exception? No.
Herein the claims as a whole are not considered to recite any additional steps or elements that amount to significantly more than well-understood, routine, and conventional activities in the art and do not add something “significantly more” so as to render the claims patent-eligible. The step of measuring a characteristic of at least one biomarker and determining a mutation in a marker gene merely instructs a scientist to use well established, routine and conventional nucleic acid techniques to gather samples for diagnostic analysis. As address in the instant specification methods of determining a characteristic or mutation analysis are well-known in the art (See para 10-11).
The step of measuring a characteristic of at least one biomarker and determining a mutation in a marker gene in at least one biological sample constitutes a data gathering step required to apply the law of nature/natural phenomenon. It is acknowledged that the claims name particular marker gene, SMAD4, whose mutation status is to be determined however the claims do not require a particular, non-conventional primer or probe consisting of or comprising a specific nucleotide sequence or any other specific reagent that is used to accomplish such determining such that the claims would recite significantly more than the judicial exception. The targets to be detected are part of the judicial exception and thereby the naming of the targets does not add something “significantly more” to the recited judicial exceptions.
The additional steps and elements are recited at a high degree of generality and are all routine, well understood and conventional in the prior art. The recited steps and elements do not provide inventive concept necessary to render the claims patient eligible. There is no combination of elements in this step that distinguishes it from well-understood, routine and conventional data gathering activity engaged in by scientists prior to applicant’s invention and at the time the application was filed. Many cited prior art references in this record demonstrate that these techniques were conventional at the time of the invention. The prior art demonstrates mutational status of SMAD4 and MEK inhibitor response (see US20190085403 and US20210355545). Thus the prior art and specification demonstrates it was routine, well-known and conventional in the art to determine mutation status of SMAD4 in biological samples. Dependent claims 5-6 further limit the recited judicial exception. Claim 2-4 and 7-8 further describe the determining steps. The dependent claims do not provide significantly more to the claims outside of the judicial exception as they encompass conventional techniques as described in the instant specification as noted above.
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.
Claims 1-9 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.
Claim 1 is vague and indefinite over the recitation of “by use of the at least one biomarker” in step (b). Step (a) requires measuring at least one characteristic of at least one biomarker, step (b) requires determining a mutation of at least one marker gene in the biological sample by use of the at least one biomarker. It is unclear what is being measured in step(a) that uses the biomarker in step (b) for determining a mutation. Is the biomarker in step (a) the marker gene in step (b) or different genes and how does using one biomarker that is different result in determining the mutation in the marker gene. It is unclear what is encompassed by biomarker, marker gene and how the biomarker is used in the determining (b).
Claims 2-9 depend from claim 1 and are indefinite for the reasons applied to claim 1.
Claim Rejections - 35 USC § 112-Written Description
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 1-9 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.
The claims are drawn to methods for determining whether to start or continue a treatment of cancer comprising measuring at least one characteristic of a biomarker in at least one biological sample comprising tumor cells, determining mutation of at least one marker gene by use of the biomarker, determining to start or continue treatment with at least one inhibitor if measuring indicates the tumor cells comprise at least one marker gene whose mutation status indicates favorable outcome wherein the one marker gene is a tumor suppressor related to the activity of TGF-β/BMR pathway. The elected marker gene is SMAD4 and dependent claims encompass MEK inhibitors.
The claims are broadly drawn to any characteristic of any biomarker, any mutation in any gene that is a tumor suppressor related to the activity of TGF-β/BMR pathway. The claims require selecting any inhibitor and require any mutation in marker gene that is related to the activity of TGF-β/BMR pathway. Additional claims require elected nonsense mutation in the marker gene, elected gene SMAD4 and MEK inhibitor.
When the claims are analyzed in light of the specification, the claims encompass methods which require analysis of the elected nonsense mutation in any marker gene that is a tumor suppressor related to the activity of TGF-β/BMR pathway and any mutation in SMAD4 in any subject with any inhibitor.
The claims encompass methods which require any mutation a tumor suppressor related to the activity of TGF-β/BMR pathway in associated with inhibitor response, where the specification is silent as to what mutations and what genes are encompassed by a tumor suppressor related to the activity of TGF-β/BMR pathway and which mutations and marker genes are associated with inhibitor treatment response. While the specification discloses marker genes SMAD4, ARID1A, FBXW7, BMPR2, and MEK gene, the specification only discloses one mutation in each of these genes and MEK inhibitor response in one patient. The specification does not provide a representative number of mutations in a representative number of tumor suppressor genes that are associated with a representative number of inhibitor response. Even with respect to MEK inhibitor, the specification only discloses one mutation in one patient. There is no description of While the specification provides examples of one patient with colorectal cancer had the mutation SMAD4 R341H, the specification does not disclose the response to MEK inhibitor or any other response to any other inhibitor (see pg. 22-24, ex 1). None of the examples provide a mutation response to a marker gene that is a tumor suppressor related to the activity of TGF-β/BMR pathway . The specification provides examples of how to identify a mutation in SMAD4 but does not disclose this mutation associated with inhibitor response in cancer to determine beginning or continuing treatment.
The claims encompass any cancer with any mutation in a marker gene that is a tumor suppressor related to the activity of TGF-β/BMR pathway and elected nonsense mutations. The specification does not disclose any nonsense mutations in any marker gene. However the specification does not provide a representative number of cancers with a representative number of mutations in a representative number of marker genes that are tumor suppressors related to the activity of TGF-β/BMR pathway. There is no disclosure of any nonsense mutation. When the claims are analyzed in light of the specification, the claims encompass a method which is directed to a determining whether to start or continue treatment of cancer by determining mutation status of marker genes that are tumor suppressors related to the activity of TGF-β/BMR pathway, the mutations and markers which is not structurally defined but requires a phenotypic class of tumor suppressors related to the activity of TGF-β/BMR pathway in cancer.
The claims encompass any genetic alteration in the elected gene SMAD4 (claim 9). The specification does not disclose a single genetic alteration in SMAD4 that is associated with an inhibitor in cancer. The specification discloses one mutation SMAD4, R361H but provides no disclosure of the mutation associated with inhibitor treatment response in a representative number of cancers. The specification does not disclose any nonsense mutations of SMAD4.
When the claims are analyzed in light of the specification, the claims encompass a method which is directed to identifying mutations which are not structurally defined in cancer phenotypes which are not described and mutations in SMAD4 which are not structurally defined but which are functionally associated tumor suppressor related to the activity of TGF-β/BMR pathway.
The genus encompassed by the claims is a broad variable genus. Claim 8 encompasses any nonsense mutation in the claimed marker gene. Claim 9 encompass any mutation in SMAD4. While the specification provides an example of one mutation in 5 genes in one individual with colorectal cancer, the specification is silent as to which of these are functionally associated with associated tumor suppressor related to the activity of TGF-β/BMR pathway and inhibitor response and which cancers are associated. Therefore, the skilled artisan would not be able of distinguishing between members of the claimed genus vs non members.
Relevant to the lack of particular structural limitations in the rejected claims drawn to nucleic acids, MPEP 2163 states:
The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.
In analysis of the claims for compliance with the written description requirement of 35 U.S.C. 112, first paragraph, the written description guidelines note regarding genus/species situations that “Satisfactory disclosure of a ``representative number'' depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed.” In the instant case, the specification fails to teach the necessary common attributes or features of the genus of encompassed nucleic acids and cancers in view of the species disclosed. The skilled artisan cannot envision the detailed chemical structure of the encompassed polynucleotides and/or proteins, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. The nucleic acid itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993), and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. As such, one of skill in the art would not recognize that applicant was in possession of the genus of nucleic acids and cancers encompassed by the broadly claimed invention. However, Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.).
Thus considering the breadth of the breadth of the claimed nucleic acids, inhibitors, cancers and their specific required functionalities, in light of the teachings of the instant specification and the art, it is the conclusion that the specification does not provide an adequate written description of the broadly claimed subject matter
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-9 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Velculescu (US20210355545 A1)
Velculescu teaches identifying a mammal as likely to response to a particular cancer treatment based on the presence or absence of one or more structural alterations. Velculescu teaches a mammal can be identified as having a cancer likely to respond to MEK inhibitors based on at least in part having one or more cancer cells having one or more modification in SMAD4 and treating the mammal with one or more MEK inhibitors (see para 32) (claim 5-6 and 9). Velculescu teaches a sample can comprise tissue sample and include DNA (see para 34) (claim 3, 4). Velculescu teaches detecting a modification in a sequence of SMAD4 (para 60) (claim 2). Velculescu teaches sequence alterations were determined by sequence changes (See para 69) (measuring characteristic of biomarker and determining mutation of marker gene). Velculescu teaches the presence of one or more structural alterations in one or more cancer cells can determine cancer treatment (see para 61) (claim 7). Velculescu teaches MEK inhibitors trametinib, cobimetinib, and selumetinib (see para 61)(claim 6). Velculescu teaches identifying nonsense or frameshift inactivating mutations in a panel of tumor suppressor genes (See para 69) (claim 8).
Claims 1-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Frampton et al. (US20190085403).
Frampton teaches a method of treating cancer by acquiring a responder status to therapy, wherein the responder status comprises a measure of mutation load in a sample, compared to reference value and administering to the subject the therapy (see para 8-11). Frampton teaches measuring mutational load includes measuring one, two or all of the following in a sample the level of somatic alteration in predetermined set of genes set forth in table 1 (comprises SMAD4), the presence or absence of somatic alteration in an NF1 gene, the number of somatic alteration in LRP1B gene, and the number of C to T transitions in genes from table 1 (see para 12-16). Frampton teaches MEK inhibitor is cobimetinib or trametinib and teaches the different therapy is administered in combination with PDL1 or PD1 therapy (see para 182, 650 and 653) (claims 5-6). Frampton teaches the mutations include nonsense mutations and teaches alterations in genes from table 1 (see para 277). Table 1 comprises SMAD4 (see table 1) (claim 8-9) . Frampton teaches biological samples comprise tumor cells and tumor nucleic acid samples, comprising DNA, cDNA a or RNA from tumor or cancer samples (see para 297) (claim 3-4). Frampton teaches measuring the sequence of the DNA, determining a mutation in SMAD4 and determining treatment (See para 275-277, 401, 441) (claim 2). Frampton teaches probes and primers to detect a mutation (use of biomarker to determine mutation) ( para 406-407). Frampton further teaches screening methods that include analysis of a biological sample from two or more tumor sites (See para 516) (claim 7).
Conclusion
No claims are allowable.
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/SARAE L BAUSCH/ Primary Examiner, Art Unit 1699