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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/20/2025 has been entered.
Affidavit or Declaration Under 37 CFR 1.132
The affidavit under 37 CFR 1.132 filed 10/20/2025 is insufficient to overcome the rejection under 35 USC 103 of claims 1 and 4-11 based upon a specific reference applied under 35 U.S.C. 103 as set forth in the last Office action because:
The 4th item in the Table 1 is not a persuasive argument, as the instant claims have nothing to do with the sampling volumes.
For the 5th-6th items, Sahin does teach extract CTCs contained in blood (Sahin: [021]). Sahin also teaches “Germline DNA or RNA is extracted from peripheral blood mononuclear cells (PBMCs) in patients with non-hematological malignancies.” (Sahin: [178]). Hence, Sahin teaches extract nucleic acids from both CTCs and normal mononuclear cells as control. The arguments regarding items 5-6 are therefore not persuasive.
For the 7th item, Hacohen does teach “an identified point mutation and has a determined binding to the HLA protein of the subject with an IC50 less than 500 nM” (Hacohen: Col 4, par 3), which overlap with the instant range of less than 100 nM for the HLA affinity.
The “HLA-agnostic method” in the 8th item in the declaration is not commensurate in scope with the claims. Claim 1 step c) read as “performing an HLA type I or II receptor affinity prediction analysis on any sequence element in the first candidate data set S1 and the second candidate data set S2 to obtain a primarily selected sequence element, the primarily selected sequence element is a sequence element that binds tightly to the HLA type I or II receptor IC50<100nM)”, which, like the Affidavit admitted in item 7, do perform the conventional HLA-I or II prediction method. On the other hand, “HLA-agnostic” is absent in the claims. Hence, the conclusion on item 8 is not persuasive.
Regarding the 9th item, the “hit rate” of 35% for the instant invention vs 3% for the reference invention (or of any conventional affinity-based methods to screen tumor neoantigens) is a subjective assertion. We don’t see the objective evidence. The last “wherein” clause (where the 35% hit rate is recited) in claim 1 is supposed to further limit a previous step (or steps) of action. However, it is not clear which of the seven steps ( step a) through step g) ) that this amendment (especially the “hit rate”) should combine to and further limit to. Further, regarding the 9th item, the limitation “increase the hit rate to 35%” is interpreted as “the hit rate is in the range of 0-35%, it can reach 35% in one embodiment (in the best case scenario).” Therefore the 3% (“using conventional affinity-based methods to screen neoantigens, the hit rate is only 3%” according to the Affidavit; also according to the 1st art applied and the 2nd art applied, as pointed out in the Affidavit) is in range of the 0-35%. For this reason, the item 9 in the affidavit is not persuasive.
Other than items 8-9, items 1-7 clearly state that the instant methods are obvious over art applied, just by read the Table 1 of the Affidavit alone.
The affidavit under 37 CFR 1.132 filed 2/5/2025 is hence insufficient to overcome the rejection under 35 USC 103 of claims 1 and 4-11.
Status of Claims
Claims 1 and 4-11 are pending and are examined on the merits.
Priority
As detailed on the 08/18/2020 filing receipt, this application claims priority to as early as 12/01/2017.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1 and 4-11 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 amendment recites “wherein the method removes background noise and increases the hit rate to 35% as compared to 3% of any conventional affinity-based methods to screen tumor neoantigens” at the end of claim 1. This amendment is interpreted as an assertion. However, it is not clear which of the seven steps ( step a) through step g) ) that this amendment should combine to and further limit to.
Claim 1 recites “(a) providing a first sample sequencing data set Al and a first control sequencing data set R1 corresponding to a subject; and providing a second sample sequencing data set A2 and a second control sequencing data set R2 corresponding to a subject, wherein the method including the following steps” at step a). It is not clear the relationship between the two “a subject” in step a).
Claim 1 recites “(a) providing a first sample sequencing data set Al and a first control sequencing data set R1 corresponding to a subject; and providing a second sample sequencing data set A2 and a second control sequencing data set R2 corresponding to a subject, wherein the method including the following steps: t1) providing a first sample, and the first sample is a sample containing a Circulating Tumor Cell (CTC) and a normal body fluid cell;” at step a) and a/t1). It is not clear the relationship between “a first sample” in step a) and “a first sample” in step a/t1).
Claim 1 recites “(a) providing a first sample sequencing data set Al and a first control sequencing data set R1 corresponding to a subject; and providing a second sample sequencing data set A2 and a second control sequencing data set R2 corresponding to a subject, wherein the method including the following steps:” and (in step t4) “providing a second sample sequencing data set A2 and a second control sequencing data set R2”. It is not clear the relationship between “a second sample” in step a) and “a second sample” in step a/t4).
Claim 1 is unclear when reciting “wherein the first sample data set is selected in a classification and/or analysis” in the 3rd “wherein” clause from the end of claim 1. It is not clear how “in a classification and/or analysis” corresponds to the steps c-g) recited in claims 1.
Claim 1 is unclear when reciting “wherein the second sample data set is selected in a classification and/or analysis” in the 2nd “wherein” clause from the end of claim 1. It is not clear how “in a classification and/or analysis” corresponds to the steps c-g) recited in claims 1.
To advance compact examination, it is interpreted as if the claimed methods get two samples from the same subject, and the two quality control formula Q1 and Q2 determines which sample sequencing data set (A1 or A2 at the same location) is chosen for downstream (steps c-g)) analysis and development. However, it is still not clear which part in the subject comes the “second sample” (we know the first sample comes from blood). According to the disclosure at the “Summary of the Invention” section, the second sample is a cell-free nucleic acids sample. Therefore, the second sample is interpreted as if coming from the sample blood sample (such as the supernatant after centrifugation).
Claim Rejections - 35 USC § 103
This rejection is maintained and modified from a previous Office action.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1 and 4-11 are rejected under 35 U.S.C. 103 as being unpatentable over Sahin (US 2022/0282322 A1; Previously cited) evidenced by Nagrath ("Isolation of rare circulating tumor cells in cancer patients by microchip technology." Nature 450.7173 (2007): 1235-1239. Previously cited), and in view of Hacohen (US 10,993,997 B2; Previously cited).
Regarding claim 1, Sahin teaches (a) the recited "providing a first sample sequencing data set Al and a first control sequencing data set Rl corresponding to a subject" at least by sequencing tumor cells and normal cells with next-generation sequencing as shown in Fig. 1. Sahin teaches (t1) the recited "providing a first sample, and the first sample is a sample containing a CTC cell and a normal body fluid cell" at least with "nucleic acids can be easily obtained from samples such as biological material ... from freshly isolated cells or from CTCs which are present in the peripheral blood of patients" ([178]). Sahin teaches (t1) obtaining normal cells at least with "Normal non - mutated genomic DNA or RNA can be extracted from normal, somatic tissue" ([178]).
Sahin teaches (t2) the recited "performing CTC cell enrichment treatment on the first sample, thereby obtaining an enriched first sample" at least by "enrich[ing] ... CTCs" ([196]) with several methods set forth in ([277]). Sahin teaches the recited "wherein in the enriched first sample, the CTC cell abundance C1>5% and the normal body fluid cell abundance C2 < 95%, based on the total number of all cells in the enriched sample" at least by performing CTC enrichment and obtaining a "purity ranging from 1-80 % " ([277]) wherein the purity range falls within a BRI of the cell abundances shown above.
The newly amended element “in the enriched first sample, the CTC cell abundance is 10-90%” overlap with this range and is anticipated by Sahin.
This enrichment method (t2) is incorporated by reference of Nagrath who shows that the purity is a "ratio of CTCs to total nucleated cells" (Figure 3 description).
Sahin teaches (t2) the recited "the ratio of the CTC cell abundance C1 to the normal body fluid cell abundance C2 is recorded as B1 (i.e., B1= C1/ C2)" at least with the above incorporation by reference teaching of Nagrath which shows this ratio.
Sahin teaches (t3) the recited "extracting DNA and/ or RNA from the enriched first sample, thereby obtaining a first nucleic acid sample, wherein the first nucleic acid sample includes a nucleic acid sample from a CTC cell and a nucleic acid from a normal body fluid cell" at least by using "high-throughput genome - wide single cell genotyping method" ([196]) for sorted CTC cells to identify genomic variants. DNA from normal cells is also obtained from peripheral blood mononuclear cells ([31]).
Sahin teaches (t4) the recited "sequencing the first nucleic acid sample, wherein the nucleic acid sample from a normal body fluid cell in the first nucleic acid sample is used as a control for the nucleic acid sample from a CTC cell" at least by performing "single cell sequencing" on isolated CTC cells ([28]) and performing "NGS" on "samples from healthy tissue ... used as positive controls" ([182]). In a BRI, body fluid cells from a control reads on healthy tissue because Sahin teaches "tissue sample, including body fluids" ([294]). Sahin teaches the recited "thereby obtaining the first sample sequencing data set Al and the first control sequencing data set RI" at least with the above teachings. Sahin teaches the recited "the first sample sequencing data set Al corresponds to the sequencing data set of a CTC cell, and the first control sequencing data set Ri corresponds to the sequencing data set of a normal body fluid cell" at least with the above teachings where sequencing a single cell CTC is performed and sequencing a healthy tissue sample from body fluid is performed as a control.
Sahin teaches sequencing nucleic acid samples as discussed above.
Sahin teaches (b) the recited "performing sequence alignment treatment on the first sample sequencing data set Al and the first control sequencing data set RI, thereby obtaining a first candidate data set S 1" at least by "aligning" reads from NGS sequencing using bwa ([372]) to a reference genome. The aligned NGS data would be a "data set" (see "data set" of [186] for example). Sahin teaches (b) the recited "wherein any sequence element in the first candidate data set S1 is an element present in the A1 but not present in the R1" at least by performing a "mutation discovery" process as illustrated in Figure 9A where DNA and RNA sequence elements identified in the tumor sequence but not the normal wild type sequence are identified.
Sahin teaches (c ) the recited "performing an HLA type I or II receptor affinity prediction analysis on any sequence element in the first candidate data set S1 ... to obtain a primarily selected sequence element, the primarily selected sequence element is a sequence element that binds tightly to the HLA type I or II receptor" at least by "The step of identifying mutations which are potentially immunogenic may comprise determining and / or ranking epitopes according to a prediction of their MHC-binding capacity, preferably MHC class I binding capacity" ([37]). Sahin teaches that "an MHC molecule is an HLA molecule" ([154]) such as an "HLA class II" receptor ([5] and [153]) and the sequence element being the peptide produced from the mutation "inhibits strong binding in MHC binding" ([398]).
Sahin teaches (d) the recited "based on the primarily selected sequence element, synthesizing a DNA, RNA, short peptide chain corresponding to the primarily selected sequence element" at least with "In the context of the present invention, mRNA may be generated by in vitro transcription from a DNA template" ([210]) thereby (e-f) synthesizing mRNA from synthesized DNA using an "in vitro transcription kit commercially available" ([210]). Additionally, "cDNA synthesis" is performed ([350]). The "synthetic RNA, which may be expressed in cells of a patient such as antigen presenting cells to produce the polypeptide" ([43]) which falls within a BRI of synthesizing the polypeptide since it is performed through in vivo translation within the patient. Additionally, Sahin teaches using "synthetic peptides" ([430]).
Sahin teaches (g) the recited "mixing the DNA, RNA, and peptide chains synthesized in the previous step with a pharmaceutically acceptable carrier to prepare a pharmaceutical composition, which is a personalized cancer vaccine" at least with "An individualized cancer vaccine comprising an RNA encoding a recombinant polyepitopic polypeptide, wherein said polypeptide comprises two or more immunogenic neo-epitopes expressed by tumor cells in a particular patient" ( claim 145) wherein the "vaccine provided according to the invention may comprise a pharmaceutically acceptable carrier" ([ 45]). Sahin teaches the recited "mixing ... " at least with "The term 'carrier' refers to an organic or inorganic component, of a natural or synthetic nature, in which the active component is combined in order to facilitate application" ([300]).
Sahin does not teach (e) the "using the synthesized ... T-cell receptor (TCR) …" and (c ) IC50 ≤ 500nM.
Hacohen teaches (c ) the recited IC50 ::S 500nM at least "with an IC50 less than 500 nM" (col. 4, par. 1), which overlap with the claimed affinity range of IC50
≤
100nM.
Hacohen teaches (e) the recited "using the synthesized DNA, RNA, and short peptide chain to perform an in vitro T-cell receptor (TCR) binding test and CDS + T cell ... to obtain 10- 30 secondarily selected sequence elements, wherein the secondly selected sequence elements can bind to TCR and activate CDS + T cells" at least as shown in Figure 7 where CDS TCR T cells are used to assay candidate neoantigens.
Hacohen identifies TCRs that bind strongly to the neoantigen in a functional assay (e.g. an in vitro assay), but that are not highly represented in the TCR repertoire as being good candidates for a neoantigen vaccine (col. 5, par. 3). Hacohen teaches that the neoantigens are synthesized (see FIG. 24) and that antigen specific T cells are selected to be "activated" (col. 36, par. 2). Hacohen teaches the length of polypeptide sequences may be about "10-50 amino acids" (col. 12, last par.) which falls within a BRI of 10-30 sequence elements.
Hacohen teaches (f) the recited "based on the secondarily selected sequence elements, synthesizing DNA, RNA and peptide chains corresponding to the secondarily selected sequence elements" at least with "a single 8-10 mer peptide for each personal neoantigen is synthesized" (col. 56, 2nd to last par.).
Regarding the first “wherein” clause after step (g), Q1 would have been obvious to a PHOSITA implementing the method of Sahin. Sahin teaches the equation below used to verify mutation detections in their dataset ([500]-[501]):
FDR = FPR/(FPR + TPR)
where FDR is the false discovery rate, FPR is false positive rate, and TPR is the true positive rate ([500]). In relation to the claim language, Q1 would relate to a False discovery rate when identifying normal (healthy cell) sequencing data because Q1 is used to classify data as CTC data. FPR would be the rate of occurrence of CTC data and TPR the frequency of normal healthy cell sequence data. A PHOSITA would be motivated to use the FDR equation of Sahin as a "classifier and visualizing the ... performance" ([500]) of the detection algorithm.
Regarding the second “wherein” clause after step (g), the clause is interpreted as further limiting the embodiment of claim 1 wherein data set 2 is selected and therefore does not limit the embodiment wherein dataset 1 is selected. Q1 would have been obvious to a PHOSITA implementing the method of Sahin. Sahin teaches the equation below used to verify mutation detections in their dataset ([500]-[501]):
FDR = FPR/(FPR + TPR)
where FDR is the false discovery rate, FPR is false positive rate, and TPR is the true positive rate ([500]). In relation to the claim language, Q2 would relate to a False discovery rate when identifying normal (healthy cell) sequencing data because Q2 is used to classify data as ctDNA and ctRNA data. FPR would be the rate of occurrence of ctDBA/ctRNA data and TPR the frequency of normal healthy cell sequence ctDNA/ctRNA data. A PHOSITA would be motivated to use the FDR equation of Sahin as a "classifier and visualizing the ... performance" ([500]) of the detection algorithm.
Regarding the last “wherein” clause “wherein the method removes background noise and increases the hit rate to 35% as compared to 3% of any conventional affinity-based methods to screen tumor neoantigens” at the end of claim 1. This amendment is interpreted as an assertion. However, it is not clear which of the seven steps ( step (a) through step (g) ) that this amendment should combine to and further limit to.
Further, the limitation “increase the hit rate to 35%” is interpreted as “the hit rate is in the range of 0-35%, it can reach 35% in one embodiment (in the best case scenario).” Therefore the 3% (“using conventional affinity-based methods to screen neoantigens, the hit rate is only 3%” according to the Affidavit; also according to the 1st art applied and the 2nd art applied, as pointed out in the Affidavit) is in range of the 0-35%. For this reason, the last “wherein” clause is obvious over Sahin and Hacohen.
Regarding claim 4, Sahin teaches the recited "the sequence element is the following group: a DNA sequence element" at least as shown in FIG. 1 "DNA profiling with NGS" is performed.
Regarding claim 5, Sahin teaches the recited "the DNA sequence element contains 2-5 DNA variants, and each DNA variant contains at least 5 short peptide chain coding sequences" at least with "non-synonymous expressed single nucleotide variations (SNVs) are identified as described herein ... N=96 mutations from (3) are selected" ([182]). Sahin teaches peptides identified by their method are "preferably ... 7-20 amino acids in length" ([114]).
Regarding claim 6, Sahin teaches the recited "the normal body fluid cell includes ... monocyte ... " at least with "In further embodiments , the cell is an antigen - presenting cell, in particular a dendritic cell, a monocyte, or macrophage" ([247]).
Regarding claim 7, Sahin teaches the recited "the body fluid includes blood ... " at least with "The bodily sample may be any tissue sample such as blood" ([21]).
Regarding claim 8, Hacohen teaches the recited "the method further includes step (hl): based on the DNA, RNA, and peptide chain synthesized in step (f), screening a single-chain antibody (scFV) that specifically binds to the secondarily selected sequence element" at least with "chimeric antigen receptors (CARs) may be used in order to generate immune responsive cells ... specific for selected targets ... First-generation CARs typically consist of a single-chain variable fragment of an antibody specific for an antigen ... scFv" (col. 34, par. 2).
Hacohen does not teach the recited "constructing and/ or expanding a T cell (CAR-T) expressing chimeric antigen receptor (CAR), wherein the CAR contains the scFV as an extracellular antigen binding domain" however this would have been obvious for a PHOSITA implementing the method of Hacohen because Hacohen teaches above that CARs generate immune responsive cells, so using scFV as a binding domain would be advantageous in generating an immune response upon binding with an antibody.
Regarding claim 9, Hacohen teaches the recited "based on the DNA, RNA, and peptide chain synthesized in step (f), screening out a T cell receptor (TCR) that specifically binds to the secondarily selected sequence element, and constructing and/ or expanding a T cell expressing the TCR (TCR-T)" at least as shown in Figure 8 where paired TCR alpha beta sequencing is performed, the TCR is incorporated into a TCR cell line through TCR cloning, and "screen engineered T cell against antigen" is performed. This process is performed based on identified "neoantigen peptide pool" as shown in FIG. 17.
Regarding claim 10, Sahin teaches the recited "based on the DNA, RNA, and peptide chain synthesized in step (f), the dendritic cell (DC) of the subject is subjected to priming treatment in vitro to obtain a primed dendritic cell" at least with "Other forms of administration envision the in vitro transfection of antigen presenting cells such as dendritic cells with nucleic acids described herein followed by administration of the antigen presenting cells" ([295]). Sahin teaches maturing the DC at least with "Dendritic cell maturation is referred to as the status of dendritic cell activation at which such antigen - presenting dendritic cells lead to T cell priming, while presentation by immature dendritic cells results in tolerance" ([126]).
Regarding claim 11, Hacohen teaches the recited "the method further comprises: co-cultivating the primed dendritic cell with the subject's T cell in vitro to prepare a DC-CTL cell" at least as shown in FIG. 2 wherein following binding of the HLA to the TCR, an antigen presenting cell and T cell are cultivated. Hacohen teaches that dendritic cells are antigen presenting cells (co. 15, par. 3).
It would have been prima facie obvious for a PHOSITA before the effective filing date of the instant application to have combined Sahin’s method of comprehensive cancer-specific mutations (Sahin: [178, 196, 277]), with Hacohen’s method of systematic TCR binding predictions and tests for the cancer-specific mutations identified (Hacohen: col. 34, par. 2; Fig. 8).. Because Sahin expected that identifying mutations which are potentially immunogenic may comprise determining and/or ranking epitopes according to a prediction of their MHC-binding capacity (Sahin: [037, 378-379]). One would reasonably expect success. Because Sahin has showed that immunization with peptides conferred in vivo tumor control in protective and therapeutic settings, qualifying mutated epitopes containing single amino acid substitutions as effective vaccines. (Sahin: [419])
Response to Applicant’s Arguments
In the remarks mailed 20 October 2025, Applicant argues based on the Table 1 in the Affidavit. In response:
The 4th item in the Table 1 is not a persuasive argument, as the instant claims have nothing to do with the sampling volumes.
For the 5th-6th items, Sahin does teach extract CTCs contained in blood (Sahin: [021]). Sahin also teaches “Germline DNA or RNA is extracted from peripheral blood mononuclear cells (PBMCs) in patients with non-hematological malignancies.” (Sahin: [178]). Hence, Sahin teaches extract nucleic acids from both CTCs and normal mononuclear cells as control. The arguments regarding items 5-6 are therefore not persuasive.
For the 7th item, Hacohen does teach “an identified point mutation and has a determined binding to the HLA protein of the subject with an IC50 less than 500 nM” (Hacohen: Col 4, par 3), which overlap with the instant range of less than 100 nM for the HLA affinity.
The “HLA-agnostic method” in the 8th item in the declaration is not commensurate in scope with the claims. Claim 1 step c) read as “performing an HLA type I or II receptor affinity prediction analysis on any sequence element in the first candidate data set S1 and the second candidate data set S2 to obtain a primarily selected sequence element, the primarily selected sequence element is a sequence element that binds tightly to the HLA type I or II receptor IC50<100nM)”, which, like the Affidavit admitted in item 7, do perform the conventional HLA-I or II prediction method. On the other hand, “HLA-agnostic” is absent in any of the instant claims. Hence, the conclusion on item 8 is not persuasive.
Regarding the 9th item, the “hit rate” of 35% for the instant invention vs 3% for the reference invention (or of any conventional affinity-based methods to screen tumor neoantigens) is a subjective assertion. We don’t see the objective evidence. The last “wherein” clause (where the 35% hit rate is recited) in claim 1 is supposed to further limit a previous step (or steps) of action. However, it is not clear which of the seven steps ( step a) through step g) ) that this amendment (especially the “hit rate”) should combine to and further limit to. Further, regarding the 9th item, the limitation “increase the hit rate to 35%” is interpreted as “the hit rate is in the range of 0-35%, it can reach 35% in one embodiment (in the best case scenario).” Therefore the 3% (“using conventional affinity-based methods to screen neoantigens, the hit rate is only 3%” according to the Affidavit; also according to the 1st art applied and the 2nd art applied, as pointed out in the Affidavit) is in range of the 0-35%. For this reason, the item 9 in the affidavit Table 1 is not persuasive.
Hence, the 103 rejection is maintained.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GUOZHEN LIU whose telephone number is (571)272-0224. The examiner can normally be reached Monday-Friday 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Larry D Riggs can be reached at (571) 270-3062. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GL/
Patent Examiner
Art Unit 1686
/LARRY D RIGGS II/Supervisory Patent Examiner, Art Unit 1686