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 .
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.
Priority
Acknowledgment is made of the present application as a proper National Stage (371) entry of PCT Application No. PCT/US2022/078953, filed 10/30/2022, which claims benefit under 35 U.S.C. 119(e) to provisional application No. 63/273,768, filed 10/29/2021.
Information Disclosure Statement
The information disclosure statement filed 12/12/2024 is being considered by the examiner.
Claim Rejections - 35 USC § 112
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 1-8, 15-16, 26, 29-30, 33, 35, 46, 48-49, 51-52, 54-56, 65, 70 and 72 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 recites “A method of analyzing a sample of an individual exhibiting no pathological symptom of a cancer, the method comprising: a) contacting the sample with a bait composition comprising a display moiety comprising a cancer neoantigenic peptide under a condition sufficient for an immune cell to bind to the display moiety; b) isolating an immune cell associated with the display moiety; and c) analyzing the isolated immune cell”.
The limitation “an individual exhibiting no pathological symptom of a cancer” is unclear. See as evidenced by the American Cancer Society “Signs and Symptoms of Cancer” (retrieved online https://www.cancer.org/cancer/diagnosis-staging/signs-and-symptoms-of-cancer.html on 8/4/2026); teaches “common signs and symptoms that may be caused by cancer: Fatigue…Weight loss or gain…sores…lumps…Pain…Skin changes…These are some of the more common signs and symptoms of cancer, but there are many others not listed here” (page 1 para. 3 and page 2 para. 1). The American Cancer Society further teaches, however, that “[m]ost signs and symptoms, even ones that could point to cancer, are more often caused by other conditions” (page 2 para. 2). Therefore, it is not clear how one can recognize an individual exhibiting no pathological symptom of a cancer because the symptoms may be from an illness that is not cancer. See also the American Cancer Society teaches that “[c]ancer signs and symptoms can depend on where the cancer is, how big it is, and how much it affects nearby organs or tissues” (page 1 para. 1). Thus, it is also not clear how one would recognize “an individual exhibiting no pathological symptom of a cancer” because the individual may be in the early stages of cancer, where the symptoms are not clearly attributed to the cancer. A person having ordinary skill in the art would not be capable of readily recognizing the metes and bounds of the claim.
Furthermore, it is not clear how the individual can be “exhibiting no pathological symptom of a cancer” while at the same time have an immune cell associated with a “cancer neoantigenic peptide” (claim 1 line 4). Note that the specification paragraph 66 discloses that “"cancer neoantigen" is a neoantigen present in a subject's tumor cell or tissue but not in the subject's corresponding normal cell or tissue”. Therefore, given that the sample associates with a cancer neoantigenic peptide, the individual would inherently also have the tumor tissue that contains said neoantigenic peptide. Notably, an individual with tumor tissue is not “exhibiting no pathological symptom of a cancer” because the tumor tissue in the individual would inherently exhibit pathological symptoms of a cancer. Given this apparent contradiction, a person having ordinary skill in the art would question the metes and bounds of the claim.
Claims 2-8, 15-16, 26, 29-30, 33, 35, 46, 48-49, 51-52, 54-56, 65, 70 and 72 are included in this rejection because they depend from rejected claim 1 but fail to clarify the scope of patent protection sought.
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 65, 70 and 72 are rejected under 35 U.S.C. 101 because the claimed invention is directed to at least one judicial exception without significantly more.
The U.S. Patent and Trademark Office recently revised the MPEP with regard to § 101 (see the MPEP at 2106). Regarding the MPEP at 2106, in determining what concept the claim is “directed to,” we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a fundamental economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical application (see MPEP § 2106.05(a)-(c), (e)-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim contains an “‘inventive concept’ sufficient to ‘transform’” the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not “well-understood, routine, conventional” in the field (see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception.
See MPEP 2106.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A JUDICIAL EXCEPTION
Step 2A, Prong 1
Claim 65 recites “A method of detecting cancer in an individual…wherein a predetermined characteristic of the isolated immune cell is indicative of cancer in the individual”.
Claim 70 recites “A method of detecting residual cancer in an individual,… wherein a predetermined characteristic of the isolated immune cell from the posttreatment sample is indicative of residual cancer in the individual”.
Claim 72 recites “method of treating a cancer in an individual, comprising a) diagnosing the individual as having cancer according to the method of claim 65”.
The natural relationship to which the claims are directed (i.e., the relation between the predetermined characteristic of the isolated immune cell and cancer) is a law of nature. Similar concepts have been held by the courts to constitute law of nature/ natural phenomena, as in the identification of a correlation between the presence of myeloperoxidase in a bodily sample (such as blood or plasma) and cardiovascular disease risk in Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017). In Mayo, the Supreme Court found that a claim was directed to a natural law, where the claim required administering a drug and determining the levels of a metabolite following administration, where the level of metabolite was indicative of a need to increase or decrease the dosage of the drug. See Mayo Collaborative Services v. Prometheus Labs., Inc., 566 U.S. 66, 74 (2012).
The instant claims are similar to those in Mayo as they involve a "relation itself [which] exists in principle apart from any human action" (id. at 77), namely the relationship between the naturally occurring immune cell and the presence of cancer.
The correlation between an immune cell and disease is a judicial exception as it exists in principle apart from any human action; the correlation itself therefore cannot form the basis for eligibility. Similarly, it is a naturally occurring phenomenon that another predetermined characteristic of the immune cell would be indicative of other types of ailments.
Claim 65 further recites “A method of analyzing a sample of an individual exhibiting no pathological symptom of a cancer” (claim 1). This limitation merely limits the individual to which the natural correlation is directed to.
Claim 70 further recites “wherein the individual has been previously treated with an anti-cancer therapy and exhibits no pathological symptom of cancer after treatment” and “wherein the
individual has been previously treated for cancer and exhibits no pathological symptom of a
cancer after the treatment” (claim 48). These limitations merely limit the individual to which the natural correlation is directed to. Therefore these are also directed to the judicial exception.
Step 2A, Prong 2
The claims also recite “a) contacting the sample with a bait composition comprising a display moiety comprising a cancer neoantigenic peptide under a condition sufficient for an immune cell to bind to the display moiety; b) isolating an immune cell associated with the display moiety; and c) analyzing the isolated immune cell” (claim 1).
Such steps of contacting the sample with the bait and isolating and analyzing the immune cell therein are insufficient to integrate the judicial exception(s) because the purpose is merely to obtain data. This does not go beyond insignificant presolution activity, i.e., a mere data gathering step necessary to use the correlation, similar to the fact pattern in In re Grams, 888 F.2d 835 (Fed. Cir. 1989) and Ariosa Diagnostics, Inc. v. Sequenom, Inc. (Fed. Cir. 2015). Furthermore, the steps of analyzing and isolating the immune cell are recited at a high level of generality and are not tied, for example, to any particular machine or apparatus.
Claim 72 further recites “subjecting the individual to anti-cancer therapy”.
This treatment step is insufficient to integrate the judicial exception as they are not limited to a particular treatment.
The recited step of “subjecting the individual to anti-cancer therapy” is recited at a high level of generality and is not limited to a particular treatment. Such highly generalized treatment limitations – which do not require any specific treatment for cancer – do not amount to sufficient practical application to provide patentability. Although a claim limitation can integrate a judicial exception by applying or using the judicial exception(s) to effect a particular treatment or prophylaxis for a disease or medical condition, in this case no specific or particular treatment is set forth.
The level of generality in the instant claims stands in contrast to the treatment claims found patent-eligible in Vanda Pharm. Inc. v. West-Ward Pharm. Int’l Ltd., 887 F.3d 1117 (Fed. Cir. 2018) and Natural Alternatives Int’l v. Creative Compounds LLC, 2017 WL 1216226 (Fed. Cir. Mar. 15, 2019). The claims at issue in Vanda recited administering a specific drug (iloperidone) at specific dosage ranges based on a patient’s genotype. Vanda, 887 F.3d at 1135. Accordingly, the court found that although the inventors recognized the relationships between iloperidone, a patient’s genotype, and QTc prolongation, what they claimed is “an application of that relationship,” i.e., “‘a new way of using an existing drug’ that is safer for patients because it reduces the risk of QTc prolongation.” Id. (quoting Mayo, 566 U.S. at 87). The Federal Circuit characterized the Vanda claims as being directed to “a specific method of treatment for specific patients using a specific compound at specific doses to achieve a specific outcome.” Id. at 1136. Similarly, the Federal Circuit found that the claims in Natural Alternatives “contain specific elements that clearly establish they are doing more than simply reciting a natural law,” such as specifying a patient population, particular results to be obtained, specific compounds to be administered to achieve the claimed results, and dosages via an “effective” limitation. Natural Alternatives, 4-5.
In contrast to the claims in Vanda and Natural Alternatives, the present claims do not specify a particular result to be obtained, a compound to be administered to achieve a claimed result, or any specific dosage of a specific compound.
Rather, “subjecting the individual to anti-cancer therapy” is instead merely an instruction to “apply” the exception in a generic way.
ELIGIBILITY STEP 2B: WHETHER THE ADDITIONAL ELEMENTS CONTRIBUTE AN "INVENTIVE CONCEPT"
The additional elements of the claims, including the steps of contacting the sample with the bait and isolating and analyzing the associated immune cell, do not add significantly more to the judicial exception(s). The step of analyzing the immune cell is recited at a high level of generality and is not limited, for example, to any specific testing technique.
Although the isolation of the immune cell is done using a bait composition comprising a display moiety comprising a cancer neoantigenic peptide, no particular or specific bait/display moiety/peptide is set forth.
Furthermore, the specification indicates that the isolation step was known in the art (see [0212], “In some embodiments, magnetic activated cell sorting, affinity chromatography, or any of the methods of cell sorting known in the art are used”). Given that isolating cells were predominant in the clinical assay art and were also in routine use, step b) does not go beyond routine/ conventional activity and fails to impose meaningful limits on the claim scope.
In this case, it was well-understood, routine and conventional to a) contacting the sample with a bait composition comprising a display moiety comprising a cancer neoantigenic peptide under a condition sufficient for an immune cell to bind to the display moiety; b) isolating an immune cell associated with the display moiety; and c) analyzing the isolated immune cell.
See for example, Peng et al. Cell Reports 28, 2728–2738, September 3, 2019 https://doi.org/10.1016/j.celrep.2019.07.106 -Cite No. 17 of IDS 12/12/2024 (“Heath”).
Heath teaches a) contacting the sample with a bait composition comprising a display moiety comprising a cancer neoantigenic peptide under a condition sufficient for an immune cell to bind to the display moiety (“sensitive method for the enumeration and isolation of neoantigen-specific CD8+ T cells from small samples of patient tumor or blood. The method relies on magnetic nanoparticles that present neoantigen-loaded major histocompatibility complex (MHC) tetramers at high avidity by barcoded DNA linkers.” Abstract); b) isolating an immune cell associated with the display moiety (“The magnetic particles provide a convenient handle to isolate the desired cell populations, and the barcoded DNA enables multiplexed analysis. The method exhibits superior recovery of antigen-specific T cell populations relative to literature approaches” Abstract); and c) analyzing the isolated immune cell (“multiplexed analysis” Abstract, “Functional and Genetic Validation of Identified Neoantigen-Specific T Cells…To validate the neoantigen-specific populations identified by NP-barcoded NACS, we analyzed functional activity by an ELISpot cell secretion assay and, for one population, carried out single-cell TCR gene sequencing” page 2734 col. 1 para. 3).
See also Peng et al. (US 20200256849 A1) Cite No. 1 of IDS 12/12/2024 (“Peng”).
Peng teaches a) contacting the sample with a bait composition comprising a display moiety comprising a cancer neoantigenic peptide under a condition sufficient for an immune cell to bind to the display moiety (“a. contacting a sample with a plurality of particle sets, i. wherein each particle of each set comprises an antigen peptide, an operably associated barcode, and at least one identifying label; ii. wherein the sample comprises T cells; and iii. wherein contacting comprises providing conditions suitable for a single T cell to bind to a unique antigen peptide of at least one particle set;” claim 1, “a neoantigen” claim 12); b) isolating an immune cell associated with the display moiety (“ b. isolating one or more T cells bound to a particle” claim 1); and c) analyzing the isolated immune cell (“c. identifying the barcode of the particle bound to the isolated T cell; and d. determining a ratio of each barcode; and e. determining the antigen specificity of the T cell” claim 1).
Furthermore, Hacohen et al. (US 10,993,997 B2) (“Hacohen”). Hacohen teaches a) contacting the sample with a bait composition comprising a display moiety comprising a cancer neoantigenic peptide under a condition sufficient for an immune cell to bind to the display moiety (“These mutFNDC3B-specific T cells could be detected by neoantigen-specific tetramers (FIG. 20B)” col. 50 lines 65-67); b) isolating an immune cell associated with the display moiety (“isolated naive and memory CD4+ and CD8+ T cells from peripheral blood mononuclear cells (PBMC)” col. 50 lines 3-7); and c) analyzing the isolated immune cell (Fig. 20B see the flow cytometry analysis of the isolated immune cell).
In view of the above evidence, the claimed steps a)-c) do not add any feature that is more than well-understood, purely conventional, or routine in the field of diagnostics and biochemical assay methodologies.
There is also evidence of record to indicate that the additional elements, alone or in combination, do not go beyond well-understood, routine and conventional activity in that others had previously analyzed immune cells in patients and also treated with anti-cancer therapy in the same patients.
See for example Heath further teaches that they “applied the method to profile neoantigen-specific T cell populations in the tumor and blood of patients with metastatic melanoma over the course of anti-PD1 checkpoint inhibitor therapy” (Abstract).
See also Peng teaches “[a] method of treating cancer in a subject, comprising:…b. contacting the plurality of particles with a plurality of T cells from the subject under conditions suitable for antigen-specific binding of a T cell to the particle; c. isolating the T cells bound to the particle and identifying a TCR gene sequence of the isolated T cell…administering a therapeutically effective number of the modified T cells to the subject to thereby treat the cancer” (claim 30).
Furthermore, Hacohen teaches subjecting the individual to anti-cancer therapy (“Therefore, it is an object of the present invention to treat a subject in need thereof with T cells expressing personalized T cell receptors to provide a subject specific and effective therapy” col. 2 lines 39-42, “treating the subject for cancer” col. 4 lines 38-39).
Unlike the claims in Vanda Pharm. Inc. v. West-Ward Pharm. Int’l Ltd (Fed. Cir. 2018, which were directed to a specific method of treatment for specific patients using a specific compound at specific doses to achieve a specific outcome (see Vanda decision at page 32, second paragraph), the instant claims, like those in Mayo, while including a treatment step cannot be clearly categorized as being directed to a specific method of treatment; and the treatment steps fail to add significantly more for reasons noted above.
For all of these reasons, the claims fail to include additional elements that are sufficient to amount to significantly more than the judicial exception(s).
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.
Claims 1-8, 15-16, 26, 29-30, 33, 35, 46, 49, 51 and 54-56 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Peng et al. (US 20200256849 A1) Cite No. 1 of IDS 12/12/2024 (“Peng”).
Regarding claim 1, although the claim is indefinite (see 112b rejection above), in the interest of compact prosecution, the claim is interpreted as reciting “an individual
Peng teaches a method of analyzing a sample of an individual (“compositions and methods for identification of antigen specific T cells” Title, “the sample is selected from a blood sample, a bone marrow sample, a tissue sample, a tumor sample, or a peripheral blood mononuclear cell (PBMC) sample” para. 40 “methods useful for identifying whether neoantigen specific T cells are present in a patient sample can be used in combination with the methods described here” para. 350), the method comprising: a) contacting the sample with a bait composition comprising a display moiety comprising a cancer neoantigenic peptide under a condition sufficient for an immune cell to bind to the display moiety (“Disclosed herein are antigenic peptide-MHC complexes, termed comPACT polypeptides …their exemplary use in capturing cancer neoepitope-reactive T cells with high accuracy. Dual particle detection approaches for detection of neoantigen specific T cells with improved sensitivity and specificity are provided. Signal to noise ratio analysis of isolated T cells for detection of neoantigen-specific T cells with improved T cells is also provided” Abstract, “neoantigen is linked to an MHC complex” para. 277, “Incubation of the comPACT-neoID library with patient samples” para. 378); b) isolating an immune cell associated with the display moiety (“The comPACT library described herein has been used to isolate antigen specific T cells and can be used to isolate any cell that presents a neoantigen” para. 371); and c) analyzing the isolated immune cell (Abstract, “is followed by fluorescent-activated cell sorting (FACS)” para. 378).
Regarding claim 2, Peng further teaches wherein the method further comprises culturing the isolated immune cell prior to the analyzing step (“The neoTCR expressing T cells were expanded in medium containing IL2, IL7, IL15, or combinations thereof for 14 days. At the end of the expansion, the T cells preserved a "younger" T cell phenotypes, resulting in NeoTCR-Pl T cells that exhibit T memory stem cell and T central memory cell phenotypes” para. 604).
Regarding claim 3, Peng further teaches wherein the display moiety comprises two or more neoantigenic peptides (“These complexes are termed "comPACT proteins" and can then be, e.g., linked to a particle, barcoded particle, or surface for use in isolation and identification of patient-specific T cell populations targeted to patient-specific neoantigens” para. 277, “multiple comPACT proteins are attached to a particle” para. 334).
Regarding claim 4, Peng further teaches wherein the display moiety comprises four neoantigenic peptides (“The comPACT proteins can also be assembled into tetramers” para. 338).
Regarding claim 5, Peng further teaches wherein the two or more neoantigenic peptides in the display moiety are the same (“distinct particle set comprising a unique antigen peptide (as used herein referring to the comPACT)” para. 341).
Regarding claim 6, Peng further teaches wherein the neoantigenic peptide has a mutation relative to a wildtype peptide (“"Neoantigen" refers to an antigen that has at least one alteration that makes the neoantigen or presentation of the neoantigen distinct from its corresponding wild-type antigen, e.g., mutations in the polypeptide sequence, differences is post-translation modifications or differences in expression level” para. 246).
Regarding claim 7, Peng further teaches wherein the neoantigenic peptide has low immunogenicity (“HLA-peptide monomer ‘Low affinity ( μM) BINDING” Fig. 62).
Regarding claim 8, Peng further teaches wherein the wherein the display moiety comprises an MHC molecule complexed with the neoantigenic peptide (“antigenic peptide-MHC complexes, termed comPACT polypeptides” Abstract, “neoantigen is linked to an MHC complex” para. 277).
Regarding claim 15, Peng further teaches wherein the display moiety comprises two or more different kinds of MHC class I molecules selected from the group consisting of HLA-A* 24:02, HLA-A*ll:01, HLA-A*02:01, and HLA-A*03:01 (“"comPACT Library" and "comPACT-neoID Library" are used interchangeably and mean one or more compact” para. 234, “multiple comPACT proteins are attached to a particle” para. 334, “In some instances, aggregates of the particles with fluorophore labels can result in single fluorophore high mean fluorescent intensity of stained cells during isolation” para. 397, “a library of 243 comPACTs (neoepitope-HLA complexes) was produced across HLA-A*03:01, A*24:02, and C*12:03, as described in Examples 10 and 11” para. 601). Note that although Peng fails to use the language “wherein the display moiety comprises two or more different kinds of MHC class I molecules selected from the group consisting of HLA-A* 24:02, HLA-A*ll:01, HLA-A*02:01, and HLA-A*03:01” the teaching that the neoepitope-HLA complexes comprise HLA-A*03:01 and A*24:02 in the library used to isolate the T cells inherently provides “wherein the display moiety comprises two or more different kinds of MHC class I molecules selected from the group consisting of HLA-A* 24:02, HLA-A*ll:01, HLA-A*02:01, and HLA-A*03:01”.
Regarding claim 16, Peng further teaches wherein the display moiety comprises a particle (Abstract, para. 277, para. 334, Fig. 62).
Regarding claim 26, Peng further teaches wherein the display moiety further comprises a detectable label (“the particle further comprises an identifying label” para. 77).
Regarding claim 29, Peng further teaches wherein the isolating step comprises separating immune cells associated with the display moiety from the rest of the sample (“comPACT-bound T cells can be also separated by FACS into individual collection containers” para. 407).
Regarding claim 30, Peng further teaches wherein the isolated immune cell is selected from the group consisting of: a cytotoxic T cell and a memory T cell (“At the end of the expansion, the T cells preserved a "younger" T cell phenotypes, resulting in NeoTCR-Pl T cells that exhibit T memory stem cell and T central memory cell phenotypes” para. 604, “ The neoTCR expressing T cells demonstrated strong killing of the matched tumor cells at both T cell :tumor cell ratios tested (1:1 and 5:1 (data not shown))” para. 635).
Regarding claim 33, Peng further teaches wherein the isolated immune cell is in a mixture of immune cells (“The comPACT library described herein has been used to isolate antigen specific T cells and can be used to isolate any cell that presents a neoantigen. A diagram of a T cell isolation process, according to an embodiment, is shown in FIG. 26” para. 371, see Fig. 26 showing FACS data of a mixture of immune cells).
Regarding claim 35, Peng further teaches wherein analyzing the isolated immune cell comprises: (a) detecting the isolated immune cell; (b) quantifying the isolated immune cell (“Incubation of the comPACT-neoID library with patient samples (6) is followed by fluorescent-activated cell sorting (FACS)” para. 378); (c) sequencing one or more nucleic acids in the isolated immune cell, wherein analyzing the isolated immune cell further comprises analyzing the sequences of the one or more nucleic acids, wherein the one or more nucleic acids is a TCR sequence (“After isolation of comPACT-bound T cells into single-cell reaction vessels ( e.g., isolated in individual well or droplets), the nucleic acid of the comPACT-bound T cell can be further processed for downstream analysis. Specifically, the expressed TCRa and TCR~ mRNA transcripts can be first converted to cDNA by reverse transcription and the cDNA amplified for next generation sequencing (NGS) methods known to those skilled in the art” para. 409); and/or (d) subjecting the isolated immune cell to mass spectrometry analysis (“Additional examples of methods to identify neoantigens include combining sequencing with mass-spectrometry and MHC presentation prediction” para. 350).
Regarding claim 46, Peng further teaches wherein the individual has not previously been diagnosed as having cancer (“Next, a comPACT element library was used to analyze a healthy donor's PBMCs” para. 587).
Regarding claim 49, Peng further teaches wherein the individual is a human (“the individual or subject is a human” para. 240).
Regarding claim 51, Peng further teaches wherein the sample is selected from the group consisting of: blood, plasma, and a peripheral blood mononuclear cell (PBMC) sample (“the sample is selected from a blood sample, a bone marrow sample, a tissue sample, a tumor sample, or a peripheral blood mononuclear cell (PBMC) sample” para. 40).
Regarding claim 54, Peng further teaches wherein the bait composition comprises a plurality of different display moieties (“(5) A library of tetramers” para. 377, see Fig. 26 showing the bait composition comprising a plurality of different display moieties).
Regarding claim 55, Peng further teaches wherein the each of the plurality of different display moieties in the bait composition comprises a different neoantigenic peptide (Next, parallel expression of multiple comPACT constructs was assessed. Eight different comPACT constructs with different neoantigens (neoantigens 10, 15, 64, 65, 66, 67, 80, and 83) were expressed in 30 mL shaker flasks as a mid-throughput assay (FIG. 11)” para. 522).
Regarding claim 56, Peng further teaches wherein the plurality of different display moieties in the bait composition comprises at least two different display moieties, each comprising a different MHC molecule (“Embodiments of the method disclosed herein are directed to a method of manufacturing a single molecule in which a selected neoantigen is linked to an MHC complex comprising a β2-microglobulin (β2M) and an MEW heavy chain. Different MHC heavy chains can be linked to the β2M molecule to form a varying number of MEW templates. The methods disclosed herein of inserting a neoantigen into an MEW template via restriction digest or PCR-based assembly by utilizing universal target sequences flanking the neoepitope insertion site (also referred to as the neoantigen insertion site) results in the ability to construct a library of different neoantigen-MHC complexes in a high-throughput method that can be personalized for a given patient” para. 277).
Claims 1-6, 8, 26, 29-30, 33, 35, 46, 48-49, 51, 65, 70 and 72 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Hacohen et al. (US 10,993,997 B2) (“Hacohen”).
Regarding claim 1, although the claim is indefinite (see 112b rejection above), in the interest of compact prosecution, the claim is interpreted as reciting “an individual
Hacohen teaches a method of analyzing a sample of an individual (“Methods for profiling the T cell repertoire” Title, “The present disclosure relates to methods for profiling subject specific and personalized T cell receptor (TCR) repertoires using a single-cell sequencing method. More particularly, disclosed are methods for determining binding of T cell receptors to subject specific neoantigens. In addition, the techniques herein may identify the antigenic targets of T cell receptors in the context of tumor neoantigens” Abstract, “T cells can be obtained from a number of sources, including peripheral blood mononuclear cells, bone marrow, lymph node tissue, spleen tissue, and tumors” col. 17 lines 23-25), the method comprising: a) contacting the sample with a bait composition comprising a display moiety comprising a cancer neoantigenic peptide under a condition sufficient for an immune cell to bind to the display moiety (“Sorting or positively selecting antigen-specific cells can be carried out using peptide-MHC tetramers (Altman, et al., Science. 1996 Oct. 4; 274(5284):94-6).…with any MHC molecule of interest and any antigen of interest as described herein. In a preferred embodiment, neoantigens are used” col. 20 lines 1-3 and 10-12); b) isolating an immune cell associated with the display moiety (“Once T cells are isolated the TCRs present on individual cells may be determined” col. 21 lines 27-28); and c) analyzing the isolated immune cell (“TCRs are determined by incubating PBMCs with neoantigens followed by sequencing of the TCR repertoire as described herein” col. 25 lines 20-22, “a specific epitope is bound to synthetic tetrameric forms of fluorescent labeled MHC Class I molecules. Since CD8+ T cells recognize antigen in the form of short peptides bound to Class I molecules, cells with the appropriate T cell receptor will bind to the labeled tetramers and can be quantified by flow cytometry” col. 32 lines 22-30).
Regarding claim 2, Hacohen further teaches wherein the method further comprises culturing the isolated immune cell prior to the analyzing step (“In one embodiment of the invention, the method further comprises expanding the numbers of T cells in the enriched cell population” col. 20 lines 60-62).
Regarding claims 3-5 and 8, Hacohen further teaches wherein the display moiety comprises two or more neoantigenic peptides, wherein the display moiety comprises four neoantigenic peptides, wherein the two or more neoantigenic peptides in the display moiety are the same, wherein the display moiety comprises an MHC molecule complexed with the neoantigenic peptide (col. 32 lines 22-30).
Regarding claim 6, Hacohen further teaches wherein the neoantigenic peptide has
a mutation relative to a wildtype peptide (col. 20 lines 1-3 and 10-12, “"Neo-antigen" or "neo-antigenic" means a class of tumor antigens that arises from a tumor-specific mutation(s) which alters the amino acid sequence of genome encoded proteins” col. 9 lines 59-61).
Regarding claim 26, Hacohen further teaches wherein the display moiety further comprises a detectable label (col. 32 lines 22-30, “cells with the appropriate T cell receptor will bind to the labeled tetramers and can be quantified by flow cytometry” col. 32 lines 28-30).
Regarding claim 29, Hacohen further teaches wherein the isolating step comprises separating immune cells associated with the display moiety from the rest of the sample (“the cells are separated by cell sorting” col. 2 line 58, (“Sorting or positively selecting antigen-specific cells” col. 20 lines 1-3).
Regarding claim 30, Hacohen further teaches wherein the isolated immune cell is a cytotoxic T cell ( “Cytotoxic T cells recognize these antigens and kill the cells that harbor the antigens” col. 15 lines 26-28).
Regarding claim 33, Hacohen further teaches wherein the isolated immune cell is in a mixture of immune cells (“T cells can be obtained from a number of sources, including peripheral blood mononuclear cells, bone marrow, lymph node tissue, spleen tissue, and tumors” col. 17 lines 23-25).
Regarding claim 35, Hacohen further teaches wherein analyzing the isolated immune cell comprises: (a) detecting the isolated immune cell or (b) quantifying the isolated immune cell (“cells with the appropriate T cell receptor will bind to the labeled tetramers and can be quantified by flow cytometry” col. 32 lines 28-30).
Regarding claim 46, Hacohen further teaches wherein the individual has not previously been diagnosed as having a cancer (“the techniques herein may identify the antigenic targets of T cell receptors in the context of tumor neoantigens. Additionally, the present disclosure enables the discovery of T cell targets in numerous diseases, with implications for understanding the basic mechanisms of the mammalian immune response and for developing antigen-specific diagnostic markers” col. 14 lines 60-66, “the PBLs are from a healthy subject that has not had cancer previously” col. 31 lines 22-23).
Regarding claim 48, Hacohen further teaches wherein the individual has been previously treated for cancer and exhibits no pathological symptom of a cancer after the treatment (“Applicants isolated naive and memory CD4+ and CD8+ T cells from peripheral blood mononuclear cells (PBMC) of 14 patients with advanced CLL who underwent a reduced-intensity allo-HSCT” col. 50 lines 3-7, “In one CLL patient who achieved long-term remission following HSCT/whole tumor cell vaccination, Applicants found CTLs that were reactive to a predicted neoantigen peptide (from mutated but not wild-type FNDC3B)” col. 50 lines 61-65,
“These mutFNDC3B-specific T cells could be detected by neoantigen-specific tetramers (FIG. 20B)” col. 50 lines 65-67).
Regarding claim 49, Hacohen further teaches wherein the individual is human (“The term "patient" or "subject" refers to an animal which is the object of treatment, observation, or experiment. By way of example only, a subject includes, but is not limited to, a mammal, including, but not limited to, a human or a non-human mammal” col. 10 lines 45-49).
Regarding claim 51, Hacohen further teaches wherein the sample is selected from the group consisting of: blood, plasma, and a peripheral blood mononuclear cell (PMBC) sample (col. 17 lines 23-25).
Regarding claim 65, Hacohen further teaches a method of detecting cancer in an individual (“the number of cells should be sufficient to bind to a cancer antigen, or detect, treat or prevent cancer” col. 38 lines 7-9), comprising: analyzing a sample from the individual according to claim 1 (see citations above), wherein a predetermined characteristic of the isolated immune cell is indicative of cancer in the individual (“neoantigens are identified that bind to
subject specific TCRs. Neoantigens are a unique class of tumor antigen characterized by their potential to generate high avidity T cells and their exquisite tumor-specificity… The repertoire of TCRs within tumor infiltrating lymphocytes, prior to or following immunotherapy, is a measure of T cell responsiveness and reflects the repertoire of epitopes against which these T cells react.” col. 24 lines 32-35). Note that although Hacohen fails to use the language “wherein a predetermined characteristic of the isolated immune cell is indicative of cancer in the individual” the teaching of using neoantigens to detect cancer inherently provides wherein a predetermined characteristic of the isolated immune cell is indicative of cancer in the individual.
Regarding claim 70, Hacohen further teaches a method of detecting residual cancer in an individual, wherein the individual has been previously treated with an anti-cancer therapy and exhibits no pathological symptom of cancer after treatment, the method comprising analyzing a posttreatment sample from the individual according to the method of claim 48, wherein a predetermined characteristic of the isolated immune cell from the posttreatment sample is indicative of residual cancer in the individual (col. 24 lines 32-35, col. 38 lines 7-9, “Applicants isolated naive and memory CD4+ and CD8+ T cells from peripheral blood mononuclear cells (PBMC) of 14 patients with advanced CLL who underwent a reduced-intensity allo-HSCT” col. 50 lines 3-7, “In one CLL patient who achieved long-term remission following HSCT/whole tumor cell vaccination, Applicants found CTLs that were reactive to a predicted neoantigen peptide (from mutated but not wild-type FNDC3B)” col. 50 lines 61-65, “These mutFNDC3B-specific T cells could be detected by neoantigen-specific tetramers (FIG. 20B)” col. 50 lines 65-67). Note that although Hacohen fails to use the language “detecting residual cancer” and “wherein a predetermined characteristic of the isolated immune cell from the posttreatment sample is indicative of residual cancer in the individual” the teaching of detecting mutFNDC3B-specific cytotoxic T lymphocytes in a “CLL patient who achieved long-term remission following HSCT/whole tumor cell vaccination” inherently provides the “detecting residual cancer” and “wherein a predetermined characteristic of the isolated immune cell from the posttreatment sample is indicative of residual cancer in the individual”. Note that the specification paragraph 66 discloses that “"cancer neoantigen" is a neoantigen present in a subject's tumor cell or tissue but not in the subject's corresponding normal cell or tissue”. Therefore, given that the T cells associate with a cancer neoantigenic peptide, the individual would inherently also have the residual tumor tissue that contains said neoantigenic peptide.
Regarding claim 72, Hacohen further teaches a method of treating a cancer in an individual (col. 38 lines 7-9, “In a fourth aspect the present invention provides a personalized
treatment for a subject using the identified T cell repertoire. In one embodiment identification of the T cell repertoire is used to determine an immunogenic composition or vaccine to be administered to a subject in need thereof” col. 5 lines 37-41), comprising a) diagnosing the individual as having cancer according to the method of claim 65 (see citations above); and b) subjecting the individual to an anti-cancer therapy (“Moreover, the present disclosure enables the discovery of T cell targets in numerous diseases, with implications for understanding the basic mechanisms of the mammalian immune response and for developing antigen-specific diagnostic markers and therapies. Finally, cloned TCRs can be used to formulate personalized immunotherapies for those inflicted with a disease, such as cancer” Abstract).
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.
Claim 52 is rejected under 35 U.S.C. 103 as being unpatentable over Hacohen as applied to claim 1 above, and further in view of California Cancer Registry "When and What to Report (retrieved online https://ccrcal.org/submit-data/reporting-by-physicians/when-and-what-to-report/ on 8/6/2026) as evidenced by The Wayback Machine (retrieved online https://web.archive.org/web/20260000000000*/https://ccrcal.org/submit-data/reporting-by-physicians/when-and-what-to-report/ on 8/6/2026).
Regarding claim 52, Hacohen teaches the method of claim 1 as discussed above.
Hacohen further teaches diagnosing cancer (“developing antigen-specific diagnostic markers… such as cancer” Abstract, “the number of cells should be sufficient to bind to a cancer antigen, or detect, treat or prevent cancer” col. 38 lines 7-9).
Hacohen fails to teach further comprising generating a report comprising information about the cancer status in the individual.
California Cancer Registry teaches that “the California Health and Safety Code, Section 103885 has required hospitals, physicians, and certain other healthcare providers to report all new diagnoses of cancer” (page 1 para. 1). California Cancer Registry further teaches that “Confidentiality of data collected is strictly maintained in accordance with Health and Safety Code Sections 100330 and 103885; Civil Code, Section56.05 and 1798; and Federal Law PL 104-191” (page 1 para. 1). The California Cancer Registry further teaches that “Physicians should report cancer diagnoses within 30 days of first seeing the patient for cancer” (page 1 para. 2). Note that as evidenced by the Wayback machine, the California Cancer Registry reference was publicly available at least since “August 20, 2019” (page 1 para. 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Hacohen to include generating a report comprising information about the cancer status in the individual taught by the California Cancer Registry because the California Cancer Registry teaches that it is a requirement under the law. A person having ordinary skill in the art would have had a reasonable expectation of success because California Cancer Registry teaches that data confidentiality is maintained and both Hacohen and the California Cancer Registry are interested in diagnosing cancer.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claim 1, 3-6, 8, 15-16, 26, 29-30, 33, 35, 46, 48-49, 51, 54-56, 67, 70 and 72 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-45 of copending Application No. 19481061 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because copending Application No. 19481061 recites subject matter that is indistinct from the instant case.
Regarding claim 1, although the claim is indefinite (see 112b rejection above), in the interest of compact prosecution, the claim is interpreted as reciting “an individual
Copending Application No. 19481061 recites a method of analyzing a sample of an individual (“A method of analyzing a sample from one or more individuals for the presence or absence of immune cells capable of binding to an antigenic peptide” claim 1), the method comprising: a) contacting the sample with a bait composition comprising a display moiety comprising a cancer neoantigenic peptide under a condition sufficient for an immune cell to bind to the display moiety (“1) prior to immobilization, have been contacted with a bait composition comprising a display moiety comprising the antigenic peptide under a condition sufficient for an immune cell to bind to the display moiety” claim 1, “wherein the antigenic peptide is a neoantigen peptide,” claim 9); b) isolating an immune cell associated with the display moiety (“optionally wherein the method further comprises isolating immune cells bound to the display moiety or removing the display moiety or immune cells not bound to each other prior to step c)” claim 1); and c) analyzing the isolated immune cell (“c) detecting the detection agent, thereby detecting the immune cells bound to the display moiety” claim 1).
Regarding claim 3, copending Application No. 19481061 further recites wherein the display moiety comprises two or more neoantigenic peptides (claim 9, “wherein the display moiety comprises two or more antigenic peptides” claim 11).
Regarding claim 4, copending Application No. 19481061 further recites wherein the display moiety comprises four neoantigenic peptides (claim 9, “MHC tetramer” claim 13).
Regarding claim 5, copending Application No. 19481061 further recites wherein the two or more neoantigenic peptides in the display moiety are the same (“wherein the two or more antigenic peptides in the display moiety are the same” claim 11).
Regarding claim 6, copending Application No. 19481061 further recites wherein the neoantigenic peptide has a mutation relative to a wildtype peptide (claim 9).
Regarding claim 8, copending Application No. 19481061 further recites wherein the display moiety comprises an MHC molecule complexed with the neoantigenic peptide (“MHC-peptide complex” claim 13).
Regarding claim 15, copending Application No. 19481061 further recites wherein the display moiety comprises two or more different kinds of MHC class I molecules selected from the group consisting of HLA-A* 24:02, HLA-A*ll:01, HLA-A*02:01, and HLA-A*03:01 (“wherein the display moiety comprises two or more different kinds of MHC class I molecules selected from the group consisting of a) HLA-A*24: 02, HLA-A*ll: 01, HLA-A*02: 01, and HLA-A*03:01” claim 14).
Regarding claim 16, copending Application No. 19481061 further recites wherein the display moiety comprises a particle (“wherein the display moiety comprises a particle” claim 14).
Regarding claim 26, copending Application No. 19481061 further recites wherein the display moiety further comprises a detectable label (“contacting the immobilized immune cells with a detection agent recognizing the display moiety under a condition sufficient for the agent to bind to the display moiety” claim 1).
Regarding claim 29, copending Application No. 19481061 further recites wherein the isolating step comprises separating immune cells associated with the display moiety from the rest of the sample (“removing the display moiety or immune cells not bound to each other prior to step c)” claim 1).
Regarding claim 30, copending Application No. 19481061 further recites wherein the isolated immune cell is selected from the group consisting of: a cytotoxic T cell, a memory T cell, and a tumor infiltrating T cell (“wherein the immune cells are selected from the group consisting of: a cytotoxic T cell, a memory T cell, and a tumor infiltrating T cell” claim 7).
Regarding claim 33, copending Application No. 19481061 further recites wherein the isolated immune cell is in a mixture of immune cells (“the immune cells comprise a mixture of immune cells comprising T cells, B cells, macrophage cells, or dendritic cells, or combinations thereof” claim 40).
Regarding claim 35, copending Application No. 19481061 further recites wherein analyzing the isolated immune cell comprises: (a) detecting the isolated immune cell (claim 1).
Regarding claim 46, copending Application No. 19481061 further recites wherein the individual has not previously been diagnosed as having a cancer (“wherein the individual a) has not previously been diagnosed as having a cancer” claim 19).
Regarding claim 48, copending Application No. 19481061 further recites wherein the individual has been previously treated for cancer and exhibits no pathological symptom of a cancer after the treatment (“b) the individual has been previously treated for cancer and exhibits no pathological symptom of a cancer after the treatment” claim 19).
Regarding claim 49, copending Application No. 19481061 further recites wherein the individual is a human (“wherein the individual is a human” claim 18).
Regarding claim 51, copending Application No. 19481061 further recites wherein the sample is selected from the group consisting of: blood, plasma, and a peripheral blood mononuclear cell (PMBC) sample (“wherein the sample is selected from the group consisting of: blood, plasma, and a peripheral blood mononuclear cell (PBMC) sample” claim 20).
Regarding claim 54, copending Application No. 19481061 further recites wherein the bait composition comprises a plurality of different display moieties (“wherein the bait composition comprises a plurality of different display moieties” claim 21).
Regarding claim 55, copending Application No. 19481061 further recites wherein the each of the plurality of different display moieties in the bait composition comprises a different neoantigenic peptide (“e) the bait composition comprises at least 25, 50, 100, 150,200, or 250 different peptides; f) the peptides in the bait composition are associated with at least 25, 50, 75, 100, 125, 150, 175, 200, 225, or 250 different antigens; g) the bait composition comprises at least 2, 3, 4, 5, 6, or 7 different overlapping peptides associated a mutation in a gene,” claim 38).
Regarding claim 56, copending Application No. 19481061 further recites wherein the plurality of different display moieties in the bait composition comprises at least two different display moieties, each comprising a different MHC molecule (“optionally wherein the plurality of different display moieties in the bait composition comprises at least two different display moieties, each comprising a different MHC molecule” claim 21).
Regarding claim 65, copending Application No. 19481061 further recites a method of detecting cancer in an individual, comprising: analyzing a sample from the individual according to claim 1, wherein a predetermined characteristic of the isolated immune cell is indicative of cancer in the individual (“the presence of immune cells specifically binds to a bait composition comprising one or more neoantigens is indicative of the presence of a cancer” claim 23).
Regarding claim 70, copending Application No. 19481061 further recites a method of detecting residual cancer in an individual, wherein the individual has been previously treated with an anti-cancer therapy and exhibits no pathological symptom of cancer after treatment, the method comprising analyzing a posttreatment sample from the individual according to the method of claim 48, wherein a predetermined characteristic of the isolated immune cell from the posttreatment sample is indicative of residual cancer in the individual (“A method of detecting residual cancer in an individual, wherein the individual has been previously treated with an anti-cancer therapy and exhibits no pathological symptom of cancer after treatment, the method comprising analyzing a post-treatment sample from the individual according to the method of any one of claims 9-21, wherein a predetermined characteristic of the immune cell from the post-treatment sample is indicative of residual cancer in the individual” claim 24).
Regarding claim 72, copending Application No. 19481061 further recites a method of treating a cancer in an individual, comprising a) diagnosing the individual as having cancer according to the method of claim 65; and b) subjecting the individual to an anti-cancer therapy (“A method of treating a cancer in an individual, comprising a) diagnosing the individual as having cancer according to the method of claim 23; and b) subjecting the individual to an anti-cancer therapy” claim 25).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 2 and 7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-45 of copending Application No. 19481061 as applied to claim 1 above, and further in view of Peng.
Regarding claim 2, copending Application No. 19481061 recites the method of claim 1 as discussed above.
Copending Application No. 19481061 further recites a method of treating a cancer in an individual, comprising a) diagnosing the individual as having cancer according to the method of claim 23; and b) subjecting the individual to an anti-cancer therapy” (claim 25).
Copending Application No. 19481061 fails to recite wherein the method further comprises culturing the isolated immune cell prior to the analyzing step
Peng teaches a method of analyzing a sample of an individual (Title, paras. 40 and 350), the method comprising: a) contacting the sample with a bait composition comprising a display moiety comprising a cancer neoantigenic peptide under a condition sufficient for an immune cell to bind to the display moiety (paras. 277 and 378); b) isolating an immune cell associated with the display moiety (para. 371); and c) analyzing the isolated immune cell (Abstract, para. 378). Regarding claim 2, Peng further teaches wherein the method further comprises culturing the isolated immune cell prior to the analyzing step (“The neoTCR expressing T cells were expanded in medium containing IL2, IL7, IL15, or combinations thereof for 14 days. At the end of the expansion, the T cells preserved a "younger" T cell phenotypes, resulting in NeoTCR-Pl T cells that exhibit T memory stem cell and T central memory cell phenotypes” para. 604). Peng suggests that culturing the isolated immune cell prior to the analyzing step enables the determination of effective therapies (“if the labeled NeoTCR T cell can be imaged proliferating and expanding, it can be extrapolated that the NeoTCR T cell therapy is effective because the cells are differentiating into T effector cells upon target antigen encounter” para. 700).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of copending Application No. 19481061 to include the culturing step taught by Peng because Peng suggests this enables the determination of effective therapies and copending Application No. 19481061 is interested in methods of treatment. A person having ordinary skill in the art would have had a reasonable expectation of success because both copending Application No. 19481061 and Peng teach a method of analyzing a sample of an individual comprising steps a)-c).
Regarding claim 7, copending Application No. 19481061 recites the method of claim 1 as discussed above.
Copending Application No. 19481061 fails to recite wherein the neoantigenic peptide has low immunogenicity.
Peng teaches wherein the neoantigenic peptide has low immunogenicity (Fig. 62).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of copending Application No. 19481061 to rely on wherein the neoantigenic peptide has low immunogenicity taught by Peng because it would have been a simple matter of applying a known technique to a known method. In this case, both copending Application No. 19481061 and Peng teach a method of analyzing a sample of an individual comprising steps a)-c). Peng simply applies the art recognized technique of wherein the neoantigenic peptide has low immunogenicity. Therefore, a person having ordinary skill in the art would have found it obvious to apply the technique of Peng to the base method taught by both references. A person having ordinary skill in the art would have had a reasonable expectation of success because both copending Application No. 19481061 and Peng teach a method of analyzing a sample of an individual comprising steps a)-c).
Claim 52 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-45 of copending Application No. 19481061, as applied to claim 1 above, and further in view of California Cancer Registry "When and What to Report (retrieved online https://ccrcal.org/submit-data/reporting-by-physicians/when-and-what-to-report/ on 8/6/2026) as evidenced by the Wayback Machine.
Regarding claim 52, copending Application No. 19481061 recites the method of claim 1 as discussed above.
Copending Application No. 19481061 further teaches diagnosing cancer (“the presence of immune cells specifically binds to a bait composition comprising one or more neoantigens is indicative of the presence of a cancer” claim 23).
Copending Application No. 19481061 fails to recite further comprising generating a report comprising information about the cancer status in the individual.
California Cancer Registry teaches that “the California Health and Safety Code, Section 103885 has required hospitals, physicians, and certain other healthcare providers to report all new diagnoses of cancer” (page 1 para. 1). California Cancer Registry further teaches that “Confidentiality of data collected is strictly maintained in accordance with Health and Safety Code Sections 100330 and 103885; Civil Code, Section56.05 and 1798; and Federal Law PL 104-191” (page 1 para. 1). The California Cancer Registry further teaches that “Physicians should report cancer diagnoses within 30 days of first seeing the patient for cancer” (page 1 para. 2). Note that as evidenced by the Wayback machine, the California Cancer Registry reference was publicly available at least since “August 20, 2019” (page 1 para. 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of copending Application No. 19481061 to include generating a report comprising information about the cancer status in the individual taught by the California Cancer Registry because the California Cancer Registry teaches that it is a requirement under the law. A person having ordinary skill in the art would have had a reasonable expectation of success because California Cancer Registry teaches that data confidentiality is maintained and both copending Application No. 19481061 and the California Cancer Registry are interested in diagnosing cancer.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/Fernando Ivich/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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