DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendments to the claims and arguments filed on July 11, 2025 have been received and entered. Claims 1-3, 7-11, 13-14, 17, 24-26 have been amended, while claims 12 and 15 have been canceled. Claims 1-11, 13-14, 16-38 are pending in the instant application.
Election/Restrictions
Applicant’s election without traverse of claims 1-27 (group I) in the reply filed on December 12, 2023 was acknowledged.
Claims 28-38 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 12, 2023.
Priority
This application is a continuation of PCT/US2019/031743 filed on 05/10/2019, which claims priority from US provisional application no 62/688,084 filed on 06/21/2018 and US provisional 62/670,407 filed on 05/11/2018
Claims 1-11, 13-14, 16-26 and 27 are under consideration.
Withdrawn- Claim Rejections - 35 USC § 103
Claims 1-3, 5-11, 13-14, 16-19, 22-26 and 27 were rejected under 35 U.S.C. 103 as being unpatentable over Myers et al (WO2008/059252, dated 05/22/2008, art of record), Olweus et al (WO2015071763, dated 05/21/2015, art of record)/ Lorenz et al (WO2016146618, dated 09/22/2016) and Youlin et al (Cancer Letters 293 (2010) 254–262). In view of Applicants’ amendment of base claim 1, introducing the limitation “APC express a PIK3CA antigen”, as the target antigen, that is not taught by the combination of prior art, the previous rejection is rendered moot and hereby withdrawn. The claims are however subject to new rejections over the prior art of record, as set forth below.
Claims 1, 16-26 and 27 were rejected under 35 U.S.C. 103 as being unpatentable over Myers et al (WO2008/059252, dated 05/22/2008, art of record), Olweus et al (WO2015071763, dated 05/21/2015, art of record)/ Lorenz et al (WO2016146618, dated 09/22/2016), Youlin et al (Cancer Letters 293 (2010) 254–262) as applied above for claim 1 and further in view of Sohn et al (J Immunol Methods. 2014; 407: 82–89, art of record). The rejection is withdrawn for the reasons discussed above.
Claims 1, 4, 22-25 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Myers et al (WO2008/059252, dated 05/22/2008, art of record), Olweus et al (WO2015071763, dated 05/21/2015, art of record)/ Lorenz et al (WO2016146618, dated 09/22/2016), Youlin et al (Cancer Letters 293 (2010) 254–262) as applied above for claim 1, and further in view of Linnemann et al (Nature Medicine, 2013, 19, 1534-1541)/Aflk et al (Nucleic Acids Research, 2017, Vol. 45, No. 16 e148, 1-13). The rejection is withdrawn for the reasons discussed above.
Claims 1, 13-14 were rejected under 35 U.S.C. 103 as being unpatentable over Myers et al (WO2008/059252, dated 05/22/2008, art of record), Olweus et al (WO2015071763, dated 05/21/2015, art of record)/ Lorenz et al (WO2016146618, dated 09/22/2016), Youlin et al (Cancer Letters 293 (2010) 254–262) as applied above for claim 1 and further in view of Watts et al (US 20040209363, dated 10/21/2004)/Sadelain (US20130121960, dated 5/16/2013) and Munks et al (Immunology. 2004 Aug; 112(4): 559–566, art of record). The rejection is withdrawn for the reasons discussed above.
Withdrawn -Claim Rejections - 35 USC § 112
Claims 13-14 were 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. Applicant’s amendments to the claims 13 and 14 obviates the basis of the rejection.
New-Claim Rejections - 35 USC § 103- necessitated by amendments
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.
Claims 1-3, 5-11, 13-14, 16-19, 22-26 and 27 were rejected under 35 U.S.C. 103 as being unpatentable over Myers et al (WO2008/059252, dated 05/22/2008, art of record), Olweus et al (WO2015071763, dated 05/21/2015, art of record)/ Lorenz et al (WO2016146618, dated 09/22/2016), Cafri et al (WO/2018/057447, EFD, 09/23/2016) and Youlin et al (Cancer Letters 293 (2010) 254–262).
Claims ae directed to an in vitro method for identifying a T cell receptor (TCR) that targets a PIK3C antigen, the method comprising:
a) contacting a plurality of lymphocytes with a plurality of antigen presenting cells (APCs), wherein the APCs express a PIK3C antigen and at least one costimulatory ligand, and wherein the PIK3C antigen and the at least one costimulatory ligand are expressed from a single vector;
b) identifying an APC-stimulated lymphocyte; and
c) identifying a TCR expressed by the APC-stimulated lymphocyte identified in b).
With respect to claims 1-3, Myers teaches an in vitro method for identifying a T cell receptor (TCR) that targets/recognizes an antigen (abstract), comprising:
a) contacting a plurality of lymphocytes with a plurality of antigen presenting cells (APCs), wherein the APC expressing an antigen (breast cancer 5T4) (page 30, 32-33);
b) identifying and isolating lymphocyte that is stimulated by the APC (page 9, lines 20-27, lines 31-32), comprising the T cell receptors which recognizes the breast cancer antigen5T4; and
c) identifying a TCR comprised by the APC-stimulated lymphocyte identified in b) (page 9, lines 20-27, pages)
d) removing and amplifying the nucleic acid encoding said T cell receptor.
With respect to claim 2-3, Myers teaches nucleic acids capable of encoding a peptide epitope of breast cancer antigen (5T4) can be introduced into cells which are used to expand selectively cells which recognize a 5T4 antigen (see page 20, lines 31-33). Myers specifically discloses nucleic acid is capable of encoding a TCR recognizing breast cancer antigen (5T4 )could be introduced into T cells (see page 21, lines 3-4) wherein the coding sequence of nucleic acid may be a DNA or RNA (see page 21, lines 6).
Regarding claim 5, Myers teaches the method of claim 1, wherein the lymphocytes and the APCs are from a population of peripheral blood mononuclear cells of a single donor (page 9, lines32-33, page 22, lines 13-16). It is disclosed that nucleic acids encoding peptide epitopes of breast cancer antigen (5T4) can be used to transfect antigen presenting cells such as autologous dendritic cells which express the peptide epitopes endogenously.).
With respect to claim 6, Myers teaches the method, wherein the APC is a mature APC as APC is capable of expressing an MHC molecule which binds a peptide according to the invention in its peptide binding groove (page 32, lines 17-19, and pages 34, lines 18-19).
With respect to claim 7-10, Myers teaches that the antigen is a tumor associated antigen that is a small polypeptide of a breast cancer antigen 5T4 that is less than 24 amino acid residues (see page 4, lines 5-7, 15, fig. 18 and 29).
With respect to claim 11, Myers teaches that antigen 5T4 peptide may be mutated, by amino acid insertion, deletion or substitution, so long as the MHC binding-specificity of the wild-type 5T4 peptide is retained. In a preferred embodiment the modified epitope has greater affinity for the peptide binding groove. Preferably the peptide contains five or fewer mutations from the wild-type sequence (see page 17, lines 9-12).
Regarding claims 12-14, Myers teaches a method of claim 1, wherein the APC that express an antigen (5T4) further comprises costimulatory ligand that are 4-1BB: and OX40L for enhanced antitumor activity (see page 30, lines 13-15).
Regarding claims 16-19, Myers teaches identifying T cell activation by measuring a T cell proliferation (for example using 3H-thymidine incorporation) or cytokine interferon-gamma production as compared to control using ELISPOT assay (see page 19, lines 1-3).
With respect to claims 22-27, Myers teaches that the method of claim 1, wherein identifying the sequence of the specific cDNAs corresponding to the identified TCR sequences that is subsequently cloned into mammalian expression vectors and transfected into appropriate cell lines that allow expression of a recombined TCR at the cell surface to determine and confirming the binding specificity of the TCR to the antigen (see page 60, lines 4, 12). Myers teaches that the method, wherein the lymphocyte is a T cell (see page 3230, line 27).
The teaching of Myers is supported by Olweus who teaches an in vitro method for identifying a T cell receptor (TCR) that targets an antigen, comprising: (a) contacting a plurality of T cells with a plurality of antigen presenting cells (APCs), wherein the APC expresses an antigen; b) identifying a T-cell that is stimulated by the APC; and c) identifying a TCR comprised in the APC-stimulated T cells (see page 4, lines 22-33, claims 1-2 of ‘763), wherein said candidate foreign antigen is expressed by transfection of a nucleic acid construct encoding said antigens (see claim 6 of ‘763), wherein said nucleic construct is an mRNA construct (see claim 7 of ‘763). It would have been obvious to one of ordinary skill in the art to transfect APC with an DNA or mRNA in view of the teaching of Olweus. With respect to claim 7, Olweus teaches the method, wherein said candidate foreign antigen is HCV (see claim 10 of ‘763). Regarding claims 16-19, Olweus teaches the method wherein said identification comprises identifying reactive T cells by assaying IFN-gamma cytokine production following stimulation of said induced T cells with said antigen presenting cells as compared to control lymphocytes (see claim 16 of ‘763, fig. 2-3, 7). Likewise, Lorenz teaches teach a method for preparing a nucleic acid encoding the TRA and TRB of a TCR construct specific for an epitope from a defined antigen presented on a MHC, comprising (a) stimulating T cells isolated from a donor with professional antigen presenting cells presenting epitopes of said defined antigen, to enrich antigen-specific T cells; and (b) contacting said T cells with a library of cells, wherein each cell expresses a single MHC allele, wherein the library comprises cells expressing all MHC I or MHC II alleles present in the donor, and wherein the cells of said library present epitopes of said defined antigen; and (c) selecting T cells activated by said contact, preferably, based on an activation marker expressed by said activated T cells; and (d) isolating the nucleic acids encoding the TCR alpha and TCR beta chains of the TCR of said T cells (see claim 12). It is further disclosed that APCs are preferably autologous APCs as they are isolated from the same donor as the PBMCs (see page 6, para. 4).
It is relevant to note that while Myers teaches a method, wherein the APC that express an antigen (5T4) further comprises costimulatory ligand that are 4-1BB: and OX40L for enhanced antitumor activity (see page 30, lines 13-15), however, differs from claimed invention by not disclosing APC expressing an antigen is a PIK3CA antigen and at least one costimulatory ligand from a single vector.
However, before the effective filing date of instant invention, Cafri teaches targeting of neoantigens may reduce or avoid, for example, one or both of the depletion of high avidity clones directed against the antigen and the loss of T cells bearing high-affinity TCRs for their cognate antigens (see para. 24). It is further disclosed that targeting of neoantigens may provide any one or more of increased cytotoxic capacity, increased persistence in the tumor microenvironment, and decreased susceptibility to immune suppression (see para. 24). Cafri discloses targeting tumor driver gene suchas PIK3CA could result in superior results (see para. 94, example 5). Cafri teaches inducing dendritic cells from a patient to present the one or more mutated amino acid sequences; co-culturing T cells from the patient with the dendritic cells; selecting the one or more mutated amino acid sequences for which the T cells have antigenic specificity (see claim 1). It is further disclosed that the peptides of (a) have a length of about 8 to about 19 amino acid residues (see para. 32). Cafri further teaches that the nucleotide sequence(s) is introduced into the dendritic cells so that the dendritic cells express and display the one or more mutated amino acid sequences, bound to an MHC molecule, on the cell membrane. The nucleotide sequence(s) encoding the mutated amino acid may be RNA (see para. 33). The combination of references differs from claimed invention by not disclosing APC expressing a PIK3CA antigen and at least one costimulatory ligand from a single vector.
Youlin teaches transfecting APC with a vector encoding tumor-associated antigen (a truncated human prostate-specific membrane antigen and costimulatory molecule (4-1BBL) (see abstract). Youlin teaches DCs transfected with Ad-tPSMA-IRES-m4-1BBL specifically express high levels of CD80 and CD86 (see fig. 2). It is disclosed that APC (DC) transduced with Ad-tPSMA-IRES-m4-1BBL induced stronger allogeneic T-cell proliferative responses in vitro than untreated DCs (Fig. 4) and a significant increase of IFN-g production was induced by Ad-tPSMA-IRES-m4- 1BBL-transduced DCs (Fig. 5). The combination of references differs from claimed invention by not disclosing that the antigen is PIK3CA antigen.
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings of prior art to modify the method as disclosed Myers, Olweus /Lorenz by substituting the cancer antigen with another cancer PIK3CA neoantigen as disclosed in Cafri, as instantly claimed, with a reasonable expectation of success, in a method of identifying TCR that target said antigen, before the effective filing date of the instant invention. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to do so in order to reduce or avoid the depletion of high avidity clones and the loss of T cells bearing high-affinity TCRs as they are not subject to the same central tolerance mechanisms as self-antigens. It would have been further obvious to one of ordinary skill in the art to modify the method of Myers, Olweus /Lorenz by co-expressing an antigen with a costimulatory molecule from a single vector as disclosed in Youlin, for activating lymphocyte and increasing cytokine IFN-g expression, with a reasonable expectation of success. One of ordinary skill in the art would be motivated to include costimulatory molecule with antigen as signaling through costimulatory ligand 4-1BB L is known to enhances T cell expansion, and augment T cell effector function (see Myers and Youlin). Further, one of ordinary skill in the art would be motivated to co-express antigen and 4-1BB from a single vector as art recognized that genetic manipulation of APCs ( DCs) with viral vectors was considered most efficient with additional advantages of lower cost of preparation and lower levels of toxicity (see page 260, col. 2, para. 1). One of skill in the art would have been expected to have a reasonable expectation of success because prior art successfully reported (i) transfection of APCs with an PIK3C antigen (Cafri) and at least one costimulatory ligand from a single vector (Youlin). It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
Claims 1, 16-26 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Myers et al (WO2008/059252, dated 05/22/2008, art of record), Olweus et al (WO2015071763, dated 05/21/2015, art of record)/ Lorenz et al (WO2016146618, dated 09/22/2016), Cafri et al (WO/2018/057447, EFD, 09/23/2016), Youlin et al (Cancer Letters 293 (2010) 254–262) as applied above for claim 1 and further in view of Sohn et al (J Immunol Methods. 2014; 407: 82–89, art of record).
The teaching of Myers, Olweus/Lorenz< Cafri and Youlin have been discussed above and relied in same manner here. The combination of reference differs from the claimed invention by not disclosing (i) measuring the cytokine expression comprises quantitative polymerase chain reaction (qPCR) (limitation of claims 20-21).
Sohn teaches it is difficult to assess NKT cell activation by both classic RT-PCR (Figure 3 and 6B) and ELISA (Figure 6C); however, Sohn teaches detection of NKT cell activation by qPCR (see page 6D, last para.).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings of prior art to use qPCR to measure the IFN-gamma expression as disclosed by Sohn, in the method of measuring cytokine expression, as instantly claimed, with a reasonable expectation of success, before the effective filing date of the instant invention. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to do so as qPCR was shown to be more sensitive in detecting cytokine expression as compared to ELISA (see above). One of skill in the art would have been expected to have a reasonable expectation of success in measuring IFN-g expression using qPCR because prior art teaches the successful detection of IFN-gamma using qPCR. It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
Claims 1, 4, 22-25 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Myers et al (WO2008/059252, dated 05/22/2008, art of record), Olweus et al (WO2015071763, dated 05/21/2015, art of record)/ Lorenz et al (WO2016146618, dated 09/22/2016), Cafri et al (WO/2018/057447, EFD, 09/23/2016) and Youlin et al (Cancer Letters 293 (2010) 254–262). as applied above for claim 1, and further in view of Linnemann et al (Nature Medicine, 2013, 19, 1534-1541)/Aflk et al (Nucleic Acids Research, 2017, Vol. 45, No. 16 e148, 1-13).
The teaching of Myers, Cafri, Olweus/Lorenz and Youlin have been discussed above and relied in same manner here. Myers teaches that the method of claim 1, wherein identifying the sequence of the specific cDNAs corresponding to the identified TCR sequences that is subsequently cloned into mammalian expression vectors and transfected into appropriate cell lines that allow expression of a recombined TCR at the cell surface to determine and confirming the binding specificity of the TCR to the antigen (see page 60, lines 4, 12), The combination of references differs from claimed invention by not disclosing (i) performing RNA-sequencing on the lymphocyte and (ii) obtaining mRNA or genomic DNA sequence encoding TCR to validate the binding specificity.
However, before the effective filing date of instant application, it was routine to identify TCR sequences by sequencing of genomic DNA fragments encoding the TCR genes or mRNA encoding TCR. For instance, Linnemann teaches identifying TCR sequence by sequencing the genomic DNA fragments encoding the TCR gene (abstract) and then identifying antigen-specific TCRs in T cell populations (abstract). Linnemann teaches TCR-transduced PBMCs that is contacted with peptide-pulsed APC (T2 cell) that is validated for specificity of antigen binding specificity (see online method section page 1, col. 1, page 1, col. 1, para. 3). Likewise, Aflk reported single cell RNA-sequencing (scRNA-seq) that also allow simultaneous measurement of TCR sequence from a single T cell (see page 4, col. 1, para. 3, fig. 2D, Fig. 4).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings of prior art to modify the method of Myers, Youlin by identifying the TCR sequences by sequencing of genomic DNA fragments encoding the TCR genes or mRNA encoding TCR as disclosed in Linnemann/ Aflk, as instantly claimed, with a reasonable expectation of success, before the effective filing date of the instant invention. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to do so in order to assess the TCR repertoire of intertumoral T cell subsets that could be subsequently validated for antigen specificity (see above). One of skill in the art would have been expected to have a reasonable expectation of success because prior art teaches successful identification of TCR sequences by the capture and sequencing of genomic DNA fragments encoding the TCR genes as evident from the teaching of Linnemann. It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
Claims 1, 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Myers et al (WO2008/059252, dated 05/22/2008, art of record), Olweus et al (WO2015071763, dated 05/21/2015, art of record)/ Lorenz et al (WO2016146618, dated 09/22/2016), Cafri et al (WO/2018/057447, EFD, 09/23/2016) and Youlin et al (Cancer Letters 293 (2010) 254–262). as applied above for claim 1 and further in view of Watts et al (US 20040209363, dated 10/21/2004)/Sadelain (US20130121960, dated 5/16/2013) and Munks et al (Immunology. 2004 Aug; 112(4): 559–566, art of record).
The teaching of Myers, Olweus/Lorenz, Cafri, and Youlin have been discussed above and relied in same manner here. The Myers/ Olweus differs from claimed invention by not expressing two costimulatory ligands comprising 4-1BBL and OX40L from a single vector.
Watts teaches an antigen presenting cell (APC) comprising at least one costimulatory ligand (claim 1), wherein the costimulatory ligand is selected from the group consisting of 4-1 BBL and OX40L (para (0097). Sadelain provided guidance with respect to cell expressing a vector encoding a co-stimulatory ligand selected from any one or more of CD80, 4-1BBL, OX40L (see para. 7-10). Sadelain teaches use of bicistronic vector (see para. 76). Munkus reported stimulating both 4-1BB and OX40 enhanced the CD8 T-cell response more than 4-1BB alone (abstract).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings of prior art to modify the APC as disclosed in Myers, Olweus/Lorenz and Youlin by further incorporating OX40L with 4-1 BBL as disclosed in Watts/ Sadelain, as instantly claimed, with a reasonable expectation of success, before the effective filing date of the instant invention. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to do so because prior art reported incorporating co-stimulatory ligand 4-1BB and OX40 to APC enhance the CD8 T-cell response more than one -costimulatory ligand 4-1BB alone (Munkus). Further, use of bicistronic vector to deliver two co-stimulatory ligands would be obvious in view of teaching of Sadelain. One of skill in the art would have been expected to have a reasonable expectation of success in incorporating 4-1BB and OX40 because prior art successfully reported using 4-1BB and OX40 to enhance the CD8 T-cell response. It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
Response to arguments
Applicant in part agree with the suggestion from the office to limit the claim to methods for identifying a T cell receptor (TCR) that targets a PIK3CA antigen. Applicants’ arguments have been fully considered, but are not found persuasive.
In response, previous office action suggested limiting the scope of the claims to a method to identify and quantify PIK3CA TCR gene sequence from the population as disclosed in fig. 9-11 of the specification (emphasis added). In the instant case, claims are not so limited. Please note figure 9 teaches a high throughput screen and identification of PI3KCA-mutation.
The specification teaches donors were stimulated with autologous mature antigen-presenting cells transfected with mRNA encoding a 65-amino acid segment of the PIK3CA gene flanking common hotspot mutations. It is disclosed that peripheral blood mononuclear cells (PBMCs) were stimulated with autologous mature antigen-presenting cells transfected with either mRNA encoding the wild-type (WT) PIK3CA antigen or a 65-amino acid segment of the PIK3CA gene flanking common hotspot mutations such as E542K, E545K or H1047R/L in the presence of low-dose IL- 2 (90 IU/mL). The method includes identifying and isolating mutation-specific T cells followed by identifying and selecting a TCR expressed by the APC-stimulated T cells. In the instant case, claims lack specificity any specificity.
It is relevant to note that claim 1 is broad and embrace contacting a plurality of lymphocytes derived from one donor with a plurality of antigen presenting cells (APCs) from another donor, wherein the APCs express any PIK3CA antigen including a wild type PIK3CA antigen. The PI3Kα is an intracellular signaling protein involved in cell growth and survival pathways and a wild type PIK3CA cannot retrieve TCR gene sequence (emphasis added). It is emphasized that a PIK3CA hotspot mutation is required to detect a TCR because the mutation creates a neoantigen that is not present in wildtype healthy cells that are then processed and presented on the cell surface by human leukocyte antigens (HLAs). The claims as presented embrace APCs express any PIK3CA antigen including a wild type or a PIK3CA antigen comprising a hotspot mutation (see claim 11). Absent evidence of any unexpected and/or superior process of identifying TCR that target a generic PIK3CA antigen, it would be obvious for one of ordinary skill the art to modify the prior art of Myers, Olweus/Lorenz to substitute APCs expressing a cancer antigen with another neoantigen (PIK3CA) disclosed in Cafri, with reasonable expectation of success.
Therefore, in view of the fact patterns of the instant case, and the ground of rejection outlined by the examiner, applicants’ arguments are not compelling and do not overcome the rejection of record.
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 7 and 8 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 7 is indefinite as it is unclear as to how a PIK3CA antigen is a pathogen antigen. The art teaches mutation in PIK3CA represent one of the most common genetic aberrations in cancer including breast cancer (see abstract Zardavas et al. Breast Cancer Research 16:201, 1-10, 2014). In the instant case, neither instant specification nor prior art teaches PIK3CA antigen as a pathogen antigen. Therefore, scope of “PIK3CA antigen is a pathogen antigen” could not be ascertained. Likewise, recitations of PIK3CA antigen are a cancer germline antigen in claim 8 is also unclear as is an acquired (somatic) mutation that occurs in cancer cells, and not one inherited from parents. Appropriate correction is required.
Conclusion
No claims allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Grunebach et al Cancer Gene Therapy 12, 749–756 teaches co-transfection of APC with a nucleic acid encoding TAA and costimulatory molecule.
Nisa et al. (Molecular Cancer (2017) 16:93, 1-14) teach PIK3CA hotspot mutations.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ANOOP K SINGH/ Primary Examiner, Art Unit 1632