DETAILED ACTION
Comments
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 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.
Claims 1-5, 7, 14, 16-20, 22-23, 26-27, 29-33, and 42-46 are pending and examined in the instant Office action.
Withdrawn Rejections
The rejections under 35 U.S.C. 112 are withdrawn in view of amendments filed to the instant set of claims on 18 August 2025.
The rejections of claims 43-45 under 35 U.S.C. 101 are withdrawn in view of amendments filed to the instant set of claims on 18 August 2025.
The rejection of claim 45 under 35 U.S.C. 102 is withdrawn in view of amendments filed to the claim on 18 August 2025.
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.
Claim(s) 1, 3-5, 7, 14, 16-20, 22-23, 26-27, 29-33, 42, and 46 is/are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea/law of nature/natural phenomenon without significantly more. Claims 1, 3-5, 7, 14, 16-20, 22-23, 26-27, 29-33, 42, and 46 are drawn to methods.
In accordance with MPEP § 2106, claims found to recite statutory subject matter (Step 1 : YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong 1). In the instant application, the claims recite the following limitations that equate to an abstract idea:
Claim 1 recites the mental step of obtaining sequence data from a tumor.
Claim 1 recites the mental step of obtaining data representing MHC molecule polypeptide sequence data from the subject.
Claim 1 recites the mental step of inputting this data into a machine learning platform to generate a numerical probability score that the one or more tumor-specific neoantigens will elicit an immune response in the subject.
Claim 1 recites the mental step of quantifying RNA expression of the tumor-specific neoantigens in a tumor to identify tumor-specific neoantigens that express an amount of the tumor-specific antigens sufficient to elicit an immune response in the subject.
Claim 1 recites the mental step of calculating a tumor-specific neoantigen score.
Claim 1 recites the mental step of selecting one or more tumor-specific neoantigens based on the tumor-specific score for formulation of a subject-specific immunogenic composition.
Claim 5 and 7 recite the mental step of constraining the lengths of the polypeptides of the neoantigens.
Claim 14 recites the mental step that higher scores correlates with a greater probability of immunogenic response.
Claims 17-18 recite the mental steps of constraining the proportion of the tumor comprises tumor specific neoantigens.
Claims 19-20 recite the mental steps of constraining the sequence data to be nucleotide of polypeptide data.
Claims 22-23 recite the mental steps of constraining the number of tumor-specific neoantigens in the composition.
Claims 26-27 recite the mental steps of constraining the neoantigens by being encoded by short or long polypeptides.
Claim 29 recites the mental step of identifying tumor-specific neoantigens that induce an autoimmune response to normal tissue.
Claim 30 recites the mental step of not selecting one or more tumor-specific neoantigens that induce an autoimmune response to normal tissue.
Claim 31 recites the mental step of identifying one or more tumor-specific antigens that induce an autoimmune response to normal tissue that has a lower tumor-specific neoantigen score relative to a tumor-specific neoantigen that does not induce an autoimmune response.
Claims 32-33 recite the mental steps of constraining the types of cancers to which the neoantigen composition are applied.
Claim 42 recites the mental step of formulating an immunogenic composition comprising the selected one or more tumor-specific neoantigens.
Claim 46 recites the mental step of constraining the types of sequence data being analyzed.
These recitations are similar to the concepts of collecting information, analyzing it and displaying certain results of the collection and analysis in Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), organizing and manipulating information through mathematical correlations in Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)) and comparing information regarding a sample or test to a control or target data in Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014)) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)) that the courts have identified as concepts that can be practically performed in the human mind or mathematical relationships. Therefore, these limitations fall under the “Mental process” and “Mathematical concepts” groupings of abstract ideas. Merely reciting that a mental process is being performed in a generic computer environment does not preclude the steps from being performed practically in the human mind or with pen and paper as claimed. If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation of generic computer components, then if falls within the “Mental processes” grouping of abstract ideas. As such, claim(s) 1, 3-5, 7, 14, 16-20, 22-23, 26-27, 29-33, 42, and 46 recite(s) an abstract idea/law of nature/natural phenomenon (Step 2A, Prong 1 : YES).
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). This judicial exception is not integrated into a practical application because the claims do not recite an additional element that reflects an improvement to technology or applies or uses the recited judicial exception to affect a particular treatment for a condition. Rather, the instant claims recite additional elements that amount to mere instructions to implement the abstract idea in a generic computing environment or mere instructions to apply the recited judicial exception via a generic treatment.
While the claims recite preparing and even formulating an immunogenic composition intended to treat tumors, the claims do not recite the active limitation of treating the subject with the immunogenic composition. Since claim 2 recites treating the subject with the immunogenic composition, claim 2 is NOT rejected under this statute.
There are no limitations that indicate that the claimed analysis engine or the formats of the provided data require anything other than generic computing systems. As such, these limitations equate to mere instructions to implement the abstract idea on a generic computer that the courts have stated does not render an abstract idea eligible in Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. As such, claims 1, 3-5, 7, 14, 16-20, 22-23, 26-27, 29-33, 42, and 46 is/are directed to an abstract idea/law of nature/natural phenomenon (Step 2A, Prong 2 : NO).
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that equate to mere instructions to apply the recited exception in a generic way or in a generic computing environment.
The document of Lee et al. [US PGPUB 2017/0198351 A1] teaches that sequencing tumor clones is routine and conventional in the prior art.
As discussed above, there are no additional limitations to indicate that the claimed analysis engine requires anything other than generic computer components in order to carry out the recited abstract idea in the claims. Claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. MPEP 2106.05(f) discloses that mere instructions to apply the judicial exception cannot provide an inventive concept to the claims. The additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself (Step 2B : No). As such, claims 1, 3-5, 7, 14, 16-20, 22-23, 26-27, 29-33, 42, and 46 is/are not patent eligible.
Response to arguments:
Applicant's arguments filed 18 August 2025 have been fully considered but they are not persuasive.
Applicant argues that the claims recite deep learning limitations that cannot be performed in the human mind. However, the claims do not recite deep learning. The machine learning recited in the claims can comprise linear regression, which can be performed using pen and paper.
Applicant generally asserts that the claim, as integrated as a whole, results in a practical application. Even if the judicial exceptions recited are improvements to conventional judicial exceptions (i.e. conventional judicial exceptions involving analysis of cancer), the recited judicial exceptions are judicial exceptions. In addition, only dependent claim 2 (NOT rejected under this statute) involves the active limitation of treating 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.
(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.
The following rejection is reiterated:
Claim(s) 43-44 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yelensky et al. [WO 2017/106638 A1; on IDS].
Claim(s) 43-44 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Yelensky et al. [WO 2017/106638 A1; on IDS].
Claim 43 is drawn to an immunogenic composition comprising one or more tumor-specific neoantigens and an adjuvant.
Claim 44 is further limiting wherein the immunogenic composition comprises a nucleotide sequence, a polynucleotide sequence, or a cell.
The document of Yelensky et al. studies neoantigen identification, manufacture, and use [title]. The abstract of Yelensky et al. teaches producing vaccines comprising tumor-specific neoantigens. Paragraph 85 of Yelensky et al. teaches that the composition can comprise polypeptides, RNA, or dendritic cells. Paragraphs 85 and 214 of Yelensky et al. teaches that the immunogenic composition comprises adjuvant.
Response to arguments:
Applicant's arguments filed 18 August 2025 have been fully considered but they are not persuasive.
Even assuming (en arguendo) that the method of producing the product (i.e. the immunogenic composition), is different than the recited method, in a product-by-process claim, the method of producing the product does not differentiate the product from the same product produced by a second, distinct method.
Claim Rejections - 35 USC § 103
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.
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.
The following rejection is reiterated:
35 U.S.C. 103 Rejection #1:
Claim(s) 1-2, 5, 7, 14, 16, 19-20, 22-23, 26-27, 29-33, and 42-46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yelensky et al. [WO 2017/106638 A1; on IDS].
Claim 1 is drawn to a method. The method comprises obtaining sequence data from the tumor, wherein the sequence data is used to obtain data representing a polypeptide sequence of one or more tumor-specific neoantigens. The method comprises obtaining data representing MHC molecule polypeptide sequence data from the subject. The method comprises inputting the data representing the polypeptide sequences and the data representing the MHC molecule polypeptide sequences into a machine-learning platform to generate a numerical probability score that one or more tumor-specific neoantigens will elicit an immune response in the subject. The method comprises quantifying RNA expression of the one or more tumor-specific neoantigens in a tumor to identify one or more tumor-specific neoantigens that express an amount of the one or more tumor-specific neoantigens sufficient to elicit an immune response in the subject. The method comprises calculating a tumor-specific neoantigen score for the one or more tumor-specific neoantigens. The method comprises selecting one or more tumor-specific neoantigens based on the tumor-specific score for formulation of a subject-specific immunogenic composition.
Claim 2 is further limiting comprising forming a subject-specific immunogenic composition comprising the one or more selected tumor-specific neoantigens, and then administering the immunogenic composition to the subject.
Claim 48 is drawn to similar subject matter as claim 2, except claim 48 is an independent claim.
The document of Yelensky et al. studies neoantigen identification, manufacture, and use [title]. The abstract, cover figure, and claim 1 of Yelensky et al. teach selecting one or more tumor specific neoantigens from a tumor a subject for a subject-specific immunogenic composition. Paragraph 82 of Yelensky et al. teaches obtaining sequence data from a tumor wherein the sequenced data is used to obtain data representing a polypeptide sequenced of one or more tumor-specific neoantigens. Paragraphs 83, 354, and 447-455 of Yelensky et al. teach obtaining data representing MHC polypeptide sequence from the subject and inputting the polypeptide and MHC molecule data into a machine-learning platform to generate a numerical probability score that one or more tumor-specific neoantigens will elicit an immune response in the subject. Claim 13, page 40, paragraph 245, item 5, paragraphs 328 and 331, and Figure 3 (where the quantified RNA expression is entered into the encoding molecule label 314) of Yelensky et al. teach quantifying RNA expression of one or more tumor-specific neoantigens in a tumor to identify neoantigens sufficient to elicit an immune response in the subject. Claim 4 of Yelensky et al. at least suggests calculating a combined neoantigen score for one or more tumor specific neoantigens. Paragraph 200 and Figure 13J of Yelensky et al. teaches selecting one or more tumor-specific neoantigens based on the tumor-specific score. Paragraph 118 of Yelensky et al. teaches administering the formulated vaccine with tumor-specific neoantigens to the subject.
With regard to claims 5, 7, 20, and 26-27, paragraph 115 of Yelensky et al. teaches that the polypeptide sequence of the tumor-specific neoantigens is derived from/encoded by short and long polypeptides.
With regard to claim 14, paragraphs 91-92 of Yelensky et al. at least suggest that greater numerical values of scores indicate a greater probability of an immune response.
With regard to claims 16 and 19, paragraphs 444-445 of Yelensky et al. teach measuring mRNA expression.
With regard to claims 22-23, claim 2 of Yelensky et al. teaches a combination of at least about 20 tumor-specific neoantigens.
With regard to claims 29 and 31, the abstract and paragraphs 118 and 131 of Yelensky et al. teach identifying one or more tumor-specific neoantigens that induce an autoimmune response as a vaccine. Paragraphs 131 and 168 of Yelensky et al. teach that the tumor-specific neoantigens that induce and autoimmune response to normal tissue has a lower score relative to a neoantigen that does not induce an autoimmune response.
With regard to claim 30, paragraph 245, step 4b of Yelensky et al. teaches not selecting one or more tumor-specific neoantigens that induce an immune response.
With regard to claims 32-33, paragraph 187 of Yelensky et al. teaches melanoma, breast cancer, and lung cancer.
With regard to claim 42, paragraph 118 of Yelensky et al. teaches administering the formulated vaccine with tumor-specific neoantigens to the subject.
With regard to claim 46, paragraph 85 of Yelensky et al. teaches use of RNA sequence data.
It would have been obvious to someone of ordinary skill in the art at the time of the effective filing date of the instant application to modify the calculation of claim 4 of Yelensky et al. to be the recited score calculation because both scoring algorithms are alternative techniques for relating a tumor-specific neoantigen to the probability of this tumor-specific neoantigen eliciting an immune response.
Response to arguments:
Applicant's arguments filed 18 August 2025 have been fully considered but they are not persuasive.
Applicant argues that Yelensky et al. teaches away from the recited limitations. While applicant cites portions of Yelensky et al. that teach difficulties in the analysis, Yelensky et al. does not truly disparage the recited cancer analysis. While there may be difficulties, complications, and limitations in performing the claims using Yelensky et al., it is still obvious to perform all of the limitations of the claims using Yelensky et al. As an aside, the 5 percent prediction rate cited from Yelensky et al. is taken from the background section of Yelensky et al. wherein Yelensky et al. is referring to prior studies.
Applicant argues that the dependency score of Yelensky et al. teaches a likelihood that MHC is present in the neoantigen and not a direct teaching of eliciting an immunological response. In this obviousness rejection, the presence of MHC in the neoantigen suggests a likely immunological response. While paragraph 8 of Yelensky et al. may suggest limitations of using a dependency score, Yelensky et al. does not totally disparage the dependency score as being ineffective.
While applicant argues the secondary consideration of long-felt need to solve a problem, applicant does not cite evidence (i.e. in the form of data from the specification or a declaration forming a nexus with a limitation of the claims) of how this long-felt need is met. In the absence of this evidence, the argument for long-felt need is a general assertion.
The following rejection is reiterated:
35 U.S.C. 103 Rejection #2:
Claim(s) 3-4 and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yelensky et al. [WO 2017/106638 A1; on IDS] as applied to claims 1-2, 5, 7, 14, 16, 19-20, 22-23, 26-27, 29-33, and 42-46 above, in further view of Lee et al. [US PGPUB 2017/0198351 A1].
Claim 3 is further limiting comprising sequencing the tumor clones of the tumor wherein the neoantigens represent about 1% of the tumor. Claim 4 is further limiting wherein the score is calculated based on this sequencing. Claim 18 is further limiting wherein the neoantigens represent about 5% of the tumor, respectively.
The document of Yelensky et al. makes obvious formulating and administering vaccines based on neoantigen scores as likelihoods of eliciting immune responses, as discussed above. Paragraph 455 of Yelensky et al. suggests that at least 5% of the tumor is made up of neoantigens.
Yelensky et al. does not teach sequencing tumor clones of a tumor.
The document of Lee et al. studies systems and methods for analyzing circulating tumor DNA [title]. Paragraph 28 of Lee et al. teaches sequencing tumor clones.
It would have been obvious to someone of ordinary skill in the art at the time of the effective filing date of the instant application to modify the sequencing data of Yelensky et al. by use of the tumor clone sequencing of Lee et al. because it is obvious to combine known elements in the prior art to yield a predictable result. The tumor clone sequencing is an alternative to conventional sequencing. There would have been a reasonable expectation of success in combining Yelensky et al. with Lee et al. because both studies analogously pertain to sequencing tumor DNA.
Response to arguments:
Applicant's arguments filed 18 August 2025 have been fully considered but they are not persuasive.
Applicant argues that Lee et al. does not teach identification of individual neoantigens. The document of Yelensky et al. is cited to teach identification of individual neoantigens. While applicant argues that Lee et al. does not teach that tumor fractions can be used to identify tumor-specific neoantigens using the clone sequencing data, the combination of Lee et al. and Yelensky et al. at least suggests this limitation (as stated in the rejection statement above).
The following rejection is reiterated:
35 U.S.C. 103 Rejection #3:
Claim(s) 45 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yelensky et al. [WO 2017/106638 A1; on IDS] as applied to claims 43-44 above, in further view of Thanos et al. [US PGPUB 2019/0017050 A1; on attached IDS].
Claim 45 recites the immunogenic composition of claim 43, wherein the adjuvant is Poly ICLC.
The document of Yelensky et al. the immunological composition and adjuvant, as discussed above.
Yelensky et al. does not teach that the adjuvant is Poly ICLC.
Thanos et al. studies vaccines to stimulate bacteria [title]. Paragraphs 245 and 258 of Thanos et al. teaches that a possible adjuvant is Poly ICLC.
It would have been obvious to someone of ordinary skill in the art at the time of the effective filing date of the instant application to modify the immunogenic composition Yelensky et al. by use of Poly ICLC adjuvant of Thanos et al. et al. because it is obvious to combine known elements in the prior art to yield a predictable result. Poly ICLC is an alternative to the general adjuvants of Yelensky et al. There would have been a reasonable expectation of success in combining Yelensky et al. with Lee et al. because both studies analogously pertain to vaccinations and biomolecules.
E-mail Communications Authorization
Per updated USPTO Internet usage policies, Applicant and/or applicant’s representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300):
Recognizing that Internet communications are not secure, I hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. I understand that a copy of these communications will be made of record in the application file.
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Russell Negin, whose telephone number is (571) 272-1083. This Examiner can normally be reached from Monday through Thursday from 8 am to 3 pm and variable hours on Fridays.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s Supervisor, Larry Riggs, Supervisory Patent Examiner, can be reached at (571) 270-3062.
/RUSSELL S NEGIN/ Primary Examiner, Art Unit 1686 30 November 2025