DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 15 January 2026 has been entered.
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 1-2, 9-10, 12, 15, 21, 31-33, 42, 44, 47, 49, 51-52, and 56 are pending and examined in the instant Office action.
Withdrawn Rejections
The 35 U.S.C. 101 Rejection on claim 9 is withdrawn in view of amendments filed to the claim on 15 January 2026.
The prior art rejections are withdrawn in view of amendments filed to the instant set of claims on 15 January 2026.
The double patenting rejections are withdrawn in view of amendments filed to copending Application No. 16/094,786.
Claim Interpretation
Claim 10 recites the intended use of the candidate peptide as synthesis, modification, or biological testing.
Claim 32 recites the intended use of suitable peptides for preparing an immunogenic composition.
Each of claims 47 and 51 recites the intended use of a subject-specific peptide for preparing a subject-specific immunogenic composition.
Claim 52 recites an intended use of an immunogenetic composition for use in a method of inducing a tumor specific or infection specific immune response or inducing immune tolerance.
Claim 56 recites that an intended use of an engineering immune cell is to be specific for a peptide identified by the method of claim 31.
These recited intended uses in claims 32, 47, 51-52, and 56 do not differentiate the claims from the prior art.
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.
The following rejection is reiterated:
Claim(s) 10, 12, 15, 21, 31-33, 42, 44, 47, 49, and 51 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 10, 12, 15, 21, 31-33, 42, 44, 47, 49, and 51 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 10 recites the mental step of training a machine with a peptide sequence database. This training can occur using a look-up table.
Claim 10 recites the mental step of selecting, based on output of the trained prediction algorithm, a candidate peptide.
Claim 12 recites the mental step of identifying HLA allele specific binding peptides that bind to one or more additional HLA alleles.
Claim 15 recites the mental step of constraining the expression level of the source protein of a peptide within a cell to comprise determining protein levels.
Claim 21 recites the mental step of constraining the length or type of HLA allele.
Claim 31 recites the mental step of analyzing the sequence of a peptide which has been trained with a peptide sequence database.
Claim 32 recites the mental step of selecting peptides determined as capable of binding HLA proteins.
Claim 33 recites the mental step of constraining the peptides selected to bind to HLA allele motifs that are shared across two or more HLA alleles.
Claim 42 recites the mental step of constraining the subject to be suffering from a disease.
Claim 47 recites the mental step of determining mutations in the tumor DNA that are not in the non-tumor DNA.
Claim 47 recites the mental step of selecting a subject-specific peptide having a tumor neo-epitope that is epitope specific to the tumor of the subject and having a predictive score indicative of binding an HLA protein of the subject.
Claim 47 recites the mental step of comparing the sequence of peptides to a consensus sequence.
Claim 51 recites the mental step of selecting a plurality of subject-specific peptides, each having a different tumor neo-epitope that is an epitope specific to the tumor of the subject and each having a predictive score indicative of binding an HLA protein of the subject wherein the predictive score is determined by analyzing the sequence of peptide.
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) 10, 12, 15, 21, 31-33, 42, 44, 47, 49, and 51 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.
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 10, 12, 15, 21, 31-33, 42, 44, 47, 49, and 51 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 Kalaora et al. [Oncotarget, volume 7, 2016, pages 5110-5117] teaches that nucleic acid sequencing, in particular whole exome sequencing, 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. 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 10, 12, 15, 21, 31-33, 42, 44, 47, 49, and 51 is/are not patent eligible.
Response to arguments:
Applicant's arguments filed 15 January 2026 have been fully considered but they are not persuasive.
Applicant argues that the amendment of “selecting, based on output of the trained prediction algorithm, a candidate peptide for synthesis, modification, or biological testing” gives a practical application to the algorithm. This argument is not persuasive because the limitation of “for synthesis, modification, or biological testing” are intended uses of the candidate peptide and not active limitations of the claim.
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.
The following rejection is necessitated by amendment:
Claim(s) 56 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cruz et al. [Tissue Antigens, volume 64, 2004, pages 25-34].
Claim 56 is drawn to an engineered immune cell wherein the immune cell is a CD8+ T cell.
The document of Cruz et al. studies involvement of the Major Histocompatibility Complex region in the genetic regulation of circulating CD8+ T-cell numbers in humans [title]. The abstract of Cruz et al. teaches CD8+ T-cells.
Response to arguments:
Applicant's arguments filed 15 January 2026 have been fully considered but they are not persuasive.
Applicant argues that Cruz et al. does not teach the limitations of claims 1 and 31. This argument is not persuasive because claim 56 is a product-by-process claim. In other words, claim 56 is drawn to an engineered immune cell specific for a peptide. As long as the prior art teaches an engineered immune cell specific for a peptide, the process for making the engineered immune cell that is specific for a peptide does not differentiate the immune cell for the immune cell produced from any other 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 necessitated by amendment:
35 U.S.C. 103 Rejection #1:
Claim(s) 1-2 and 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Abelin et al. [Immunity, volume 46, 21 February 2017, pages 315-326; on IDS] in view of Klug et al. [Current Pharmaceutical Design, volume 15, 2009, pages 3221-3236; on IDS].
Claim 1 is drawn to a method of generating an HLA allele specific binding peptide sequence database. The method comprises providing a population of cells expressing a single HLA allele. The method comprises isolating HLA-peptide complexes from the cells. The method comprises isolating peptides from the HLA-peptide complexes. The method comprises sequencing the peptides. The HLA allele can be HLA-A*02:05, HLA-A*23:01, HLA-B*40:01, and/or HLA-B*45:01.
Claim 2 is further limiting wherein the sequencing is performed by LC-MS/MS.
Claim 9 is drawn to the database of data obtained by carrying out the method of claim 1 multiple times using different allele each time.
The document of Abelin et al. studies mass spectrometry profiling of HLA-associated peptidomes in mono-allelic cells enables more accurate epitope prediction [title]. The Methods section on page 324 of Abelin et al. and Figure 1 on page 316 of Abelin et al. illustrates providing a population of cells expressing a single HLA allele, isolating HLA-peptide complexes from the cells, isolating peptides from the HLA-peptide complexes, and using LC-MS/MS to sequence the peptides.
Abelin et al. does not teach the recited HLA alleles.
The document of Klug et al. studies characterization of MHC ligands for peptide based tumor vaccination [title]. The last full paragraph on page 3227 of Klug et al. teaches HLA-A*66:01.
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 peptide affinity assays pertaining to HLA alleles of Abelin et al. by use of the specific HLA allele of Klug et al. because it obvious to try the method of Abelin et al. across other HLA alleles. There would have been a reasonable expectation of success in combining Abelin et al. and Klug et al. because the analysis of HLA alleles of Abelin et al. is robust and generally applicable to the HLA allele of Klug et al.
Response to arguments:
Applicant's arguments filed 15 January 2026 have been fully considered but they are not persuasive.
Applicant argues that the amendments to the claims overcome Abelin et al. In response, the document of Klug et al. has been added to address the amended limitations of the claims.
The following rejection is necessitated by amendment:
35 U.S.C. 103 Rejection #2:
Claim(s) 10, 15, 42, 44, 47, and 51-52 is/are rejected under 35 U.S.C. 103 as being unpatentable over Abelin et al. in view of Klug et al. as applied to claims 1-2 and 9 above, in further view of Jurtz et al. [The Journal of Immunology, volume 199, 1 November 2017, pages 3360-3368; on IDS] in view of Bassani-Sternberg et al. [PLoS Computational Biology, volume 13, article e1005725, 28 pages; on IDS].
Claim 10 is drawn to a prediction algorithm for identifying HLA-allele specific binding peptides comprising training a machine with the peptide database of claim 9.
Abelin et al. and Klug et al. make obvious forming a database of HLA-specific binding sequences.
Abelin et al. and Klug et al. do not teach the training of machine with the database.
The document of Jurtz et al. studies improved peptide-MHC class I interaction predictions integrating eluted ligand and peptide binding affinity data [title]. The Materials and Methods section on pages 3361-3362 of Jurtz et al. teaches analogous data sets using to perform training and machine learning on peptide binding proteins.
With regard to claim 15, the paragraph bridging pages 324-325 of Abelin et al. teaches analyzing expression using peptide levels.
With regard to claims 42 and 44, the abstract of Jurtz et al. teaches application of the algorithm to the disease of cancer. Page 3366 of Jurtz et al. teaches obtaining cancer/tumor samples.
Claim 47 is drawn to a method of identifying a subject-specific peptide. The method requires that the subject has a tumor and the subject specific peptide is specific to the subject and the subject’s tumor. The method comprises nucleic acid sequencing of a sample of the subject’s tumor and a non-tumor sample of the subject. The method comprises determining based on the nucleic acid sequencing non-silent mutations present in the genome of cancer cells of the subject but nor in normal tissue from the subject. The method comprises selecting from the identified non-silent mutations one or more subject-specific peptides, each having a predictive score indicative of binding an HLA protein of the subject. The method requires that the predictive score is determined by analyzing the sequence of peptides derived from the non-silent mutations by carrying of the method of claim 31.
Claim 51 is drawn to a method for identifying a plurality of subject-specific peptides. The method comprises selecting a plurality of subject-specific peptides, each having a different tumor neo-epitope that is an epitope specific to the tumor of the subject and each having a predictive score indicative of binding an HLA protein of the subject. The predictive score is determined by analyzing the sequence of peptides derived from the non-silent mutations by carrying out the method of claim 31.
The paragraph bridging pages 324-325 of Abelin et al. teaches machine learning in the form of neural networks to determine affinities of subject-specific peptides to new epitopes using predictive scoring. Page 3366 of Jurtz et al. teaches analysis of tumor-specific mutations (i.e. mutations present in the sequencing of tumor peptides not present in wild-type peptides) to find tumor-specific sequences particular for cancer neoepitopes.
With regard to claims 52 and 56, the Methods section on page 324 of Abelin et al. and Figure 1 on page 316 of Abelin et al. illustrates peptides in water and immune cells specific to peptides.
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 peptide affinity assays pertaining to HLA alleles of Abelin et al. and the HLA allele of Klug et al. by use of applying machine learning to analyze the peptide binding pertaining the HLA alleles of Jurtz et al. wherein the motivation would have been that the machine learning is an additional mathematical tool that facilitates the analysis of peptide affinity pertaining the HLA alleles [Materials and Methods Section on pages 3361-3362 of Jurtz et al.].
There would have been a reasonable expectation of success in combining Abelin et al., Klug et al., and Jurtz et al. because all three studies are analogously applicable to analyzing the peptide affinities pertaining to HLA alleles.
The following rejection is necessitated by amendment:
35 U.S.C. 103 Rejection #3:
Claim(s) 12, 21, and 31-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Abelin et al. in view of Klug et al. in view of Jurtz et al. as applied to claims 1-2, 9-10, 15, 42, 44, 47, and 51-52 above, in further view of Bassani-Sternberg et al. [PLoS Computational Biology, volume 13, article e1005725, 28 pages; on IDS].
Abelin et al., Klug et al., and Jurtz et al. make obvious forming a database of HLA-specific binding sequences and applying machine learning to the database.
Abelin et al., Klug et al., and Jurtz et al. do not teach the all of the recited HLA alleles.
With regard to claims 12 and 21, Figure 2 on page 6 of Bassani-Sternberg et al. teaches that the four HLA alleles HLA-A*02:05, HLA-A*23:01, HLA-B*40:01, and/or HLA-B*45:01 that are conserved/shared between algorithm produced motifs and known motifs. These are HLA-A or HLA-B alleles.
With regard to claims 31-33, Figure 2 on page 6 of Bassani-Sternberg et al. teaches that the four HLA alleles HLA-A*02:05, HLA-A*23:01, HLA-B*40:01, and/or HLA-B*45:01 that are conserved/shared between algorithm produced motifs and known motifs. The Materials and Methods section on pages 3361-3362 of Jurtz et al. teaches analogous data sets using to perform training and machine learning on peptide binding proteins. The paragraph bridging pages 3361-3362 of Jurtz et al. teaches leave-one-out validation wherein a single molecule is selected, and machine learning is used to predict the affinity based on the data learned from the remaining peptides.
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 peptide affinity assays pertaining to HLA alleles of Abelin et al., the HLA allele of Klug et al., and applying machine learning to analyze the peptide binding pertaining the HLA alleles of Jurtz et al. by use of the HLA alleles of Bassani-Steinberg et al. because it obvious to try the method of Abelin et al. across other HLA alleles. There would have been a reasonable expectation of success in combining Abelin et al. and Klug et al. because the analysis of HLA alleles of Abelin et al. is robust and generally applicable to the HLA allele of Klug et al.
There would have been a reasonable expectation of success in combining Abelin et al., Klug et al., Jurtz et al., and Bassani-Sternberg et al. because all four studies are analogously applicable to analyzing the peptide affinities pertaining to HLA alleles.
Response to arguments:
Applicant's arguments filed 15 January 2026 have been fully considered but they are not persuasive.
Applicant argues that the combination of references as a whole would not make the amended claims obvious. This argument is not persuasive because the statement is a general assertion without support, and the obviousness rationale in the aforementioned rejection is still relevant.
The following rejection is necessitated by amendment:
35 U.S.C. 103 Rejection #4:
Claim(s) 49 is/are rejected under 35 U.S.C. 103 as being unpatentable over Abelin et al. in view of Klug et al. in view of Jurtz et al. as applied to claims 1-2, 9-10, 15, 42, 44, 47, and 51-52, in further view of Kalaora et al. [Oncotarget, volume 7, 2016, pages 5110-5117].
Claim 49 is further limiting wherein the nucleic acid sequencing comprises whole exome sequencing.
Abelin et al., Klug et al., and Jurtz et al. make obvious machine learning to predict peptide affinities to HLA, as discussed above.
Abelin et al., Klug et al., and Jurtz et al. do not teach whole exome sequencing.
The document of Kalaora et al. studies the use of HLA peptidomics and whole genome sequencing to identify human immunogenic neo-antigens [title].
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 peptide affinity assays pertaining to HLA alleles of Abelin et al., the specific HLA allele of Klug et al., and applying machine learning to analyze the peptide binding pertaining the HLA alleles of Jurtz et al. by use of the whole exome sequencing of Kalaora et al. wherein the motivation would have been that the whole exome sequencing is an additional empirical tool that facilitates the analysis of peptide affinity pertaining the HLA alleles [abstract of Kalaora et al.]. There would have been a reasonable expectation of success in combining Abelin et al., Klug et al., Jurtz et al., and Kalaora et al. because all five studies are analogously applicable to analyzing the peptide affinities pertaining to HLA alleles.
Response to arguments:
Applicant's arguments filed 19 May 2025 have been fully considered but they are not persuasive.
Applicant argues that the combination of references as a whole would not make the amended claim obvious. This argument is not persuasive because the statement is a general assertion without support, and the obviousness rationale in the aforementioned rejection is still relevant.
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.
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 15 March 2026