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 .
Claims Status
The Amendment filed on 30Jun2026 is acknowledged in which claim(s) 6 was/were canceled, and claim(s) 17-19 is/are new.
Claim(s) 1-5 and 7-19 is/are currently pending and presented for examination on the merits.
Response to Amendment
All previous rejections and/or objections of claim(s) 6 are moot in view of claim cancelation. The objection(s) to the specification have been withdrawn, and the rejection(s) of claim(s) # under 35 U.S.C. § 112(b), of claim(s) 1-5, 12-16 under 35 U.S.C. § 102, and of claim(s) 6-11 and 15 under 35 U.S.C. § 103 have been withdrawn in view of the recent claim amendment filed on 30Jun2026, which added new limitations to the claims, that were not considered in the previous rejections and necessitated new rejections.
As all previously presented rejection(s) and objection(s) were withdrawn, only Applicant argument(s) pertinent to new rejections as necessitated by amendment, as discussed below.
NEW REJECTIONS AS NECESSITATED BY CLAIM AMENDMENTS
Claim Rejections - 35 USC § 112(b)
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 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.
Claim(s) 19 is/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(s) 19, recite(s) “step (a) is an amount sufficient to enhance the efficacy of the PD-1 inhibitor” in line(s) 2, rendering the claim(s) indefinite. The instant specification does not define “an amount sufficient to enhance”. The support for new claim 19 as provided by Applicant in the Remarks filed on 30Jun2026 include paragraphs [0006], [0039], [0055], and [0109]. Briefly, [0006] is a brief description of the invention; [0039] is a paragraph defining the term “primer”; [0055] discusses compositions useful in treating cancer and recites “…An effective amount is an amount sufficient to elicit or augment an immune response, e.g., by activating T cells…” (e.g., no disclosure of enhancing PD1 efficacy); and [0109] is a discussion paragraph that relates to the identification and resolution of discrepancy in ICB survival based on HLA B44 in NSCLC and melanoma. Therefore, none of paragraphs [0006], [0039], [0055], or [0109] either directly or indirectly provide a definition for the phrase “an amount sufficient to enhance efficacy of PD1”. Given the lack of definition for the phrase in the instant claims and/or specification, it is unclear if the phrase means (1) different amounts of step (a) are required for different cancer types (e.g., solid, hematological), cancer indications (e.g., breast cancer, Non-Hodgkin Lymphoma), or cancer subtypes (e.g., luminal A breast cancer, luminal B breast cancer, triple negative breast cancer, DLBCL, MCL, MZL, FL, etc.); (2) different amounts of step (a) are required for different neoantigen/neoepitopes sequences present in a subject; (3) different amounts of step (a) based on individual subject history (e.g., comorbidities, tumor stage, etc.); (4) a combination of the factors above is required to determine the threshold for an “efficient amount” of step (a); (5) any amount of step (a) administered in combination with a PD1 inhibitor to treat cancer would meet the limitations; or (6) something else. For the purposes of compact prosecution, the phrase will be considered to mean “any amount” of step (a) administered in combination with a PD1 inhibitor to treat cancer. This rejection may be overcome by amending claim(s) 19 to clearly recite the limitation(s) of the instant invention.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 1-5 and 12-19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2019/0307868 A1 (hereinafter “US868”), as evidenced by Francisco et al. (Immunogenetics (2015) 67:651–663; hereinafter “Francisco”).
Regarding instant claim(s) 1-3, 16, 19, US868 teaches a method for treating cancer comprising the administration of APCs, and further teaches the APCs are autologous (e.g., obtained from subject) dendritic cells that have been pulsed with a 9mer (e.g., nonamer) neoantigen (e.g., a neopeptide associated with the cancer) [e.g., title; abstract; ¶ 0003, 0010, 0012, 0045, 0168, 0036, 0039, 0064, 0082, 0531, 0233, 0362-0363, 0429, 0481, 0562, 0563, 0656, 0612; Tables 1-2]. US868 further teaches the neoantigen(s) may comprise a secondary anchor (e.g., second position) substitution, and that substitutions may be non-conservative (e.g., radical) at the second position [e.g., ¶ 0104, 0135; 183-184, 0191, 0292-0294]. US868 further teaches the administration of a PD-1 inhibitor with the pulsed APCs (e.g., an amount sufficient to enhance the efficacy of PD1, see 112(b) rejection above for details), and an embodiment wherein the PD1 inhibitor is pembrolizumab [e.g., ¶ 0032, 0036-0039, 0082]. US868 further teaches commonly expressed HLA alleles include HLA-B alleles [e.g., ¶ 0612; tables 1-2]. The HLA B44 supertype has high average frequencies of expression in humans, and B44 is observed in all populations (e.g., the subject expresses HLA-B44), as evidenced by Francisco [e.g., pg. 656; fig. 3].
Regarding instant claim(s) 4-5, 14, US868 further teaches a nucleic acid encoding the neoepitope and that the polynucleotide may be derived from the native sequence (e.g., from sequencing subject’s biological sample) such as a tumor-associated antigen [e.g., ¶ 0122, 0124, 0360, 0423, 0481-0483, 0575]. Further, as recited above, US868 teaches the neoantigen(s) may comprise a secondary anchor (e.g., second position) substitution, and that substitutions may be non-conservative (e.g., radical) at the second position [e.g., ¶ 0104, 0135; 183-184, 0191, 0292-0294]. US868 further teaches the tumor antigen is selected from a tumor biopsy, homogenate, or lysate biological specimen [e.g., ¶ 0004, 0014, 0057]. US868 further teaches identifying anti-tumor response (e.g., identifying/observing the natural correlation that cancer is ICB-responsive when the sequencing step detects a nucleic acid encoding a nonamer neopeptide comprising a second position radical substitution) [e.g., ¶ 0038-0041, 0064, 0168, 0558, 0623, ].
Regarding instant claim(s) 12, US868 further teaches the cancer is NSCLC [e.g., ¶ 0036, 0040, 0066, 0073-0074, 0076].
Regarding instant claim(s) 13, US868 further teaches the cancer is melanoma [e.g., ¶ 0036, 0040, 0065, 0068, 0073-0076, 0530, 0534, 0537].
Regarding instant claim(s) 17, US868 further teaches that pulsing is performed on isolated dendritic cells (e.g., APCs) [e.g., ¶ 0056].
Regarding instant claim(s) 18, US868 further teaches the nucleic acid construct comprises an RNA vaccine [e.g., ¶ 0332, 0588].
Response to Arguments
Applicant argues:
“Although Claim 5 is included in this rejection, the Office Action does not identify how the cited reference teaches a ‘method of identifying a cancer as responsive to immune checkpoint blockade (ICB)’ having the features recited in Applicant’s claim 5. It is assumed that the inclusion of claim 5 in this rejection was in error”.
Cited reference fails to teach or suggest all elements of Applicant’s claims. In view of the amendments to the claims, the claimed subject matter is even further removed from the teachings of US868. Accordingly, the rejection should be withdrawn.
In response to 1 above, Applicant’s arguments rely on language solely recited in preamble recitations in claim(s) 5. When reading the preamble in the context of the entire claim, the recitation of a ‘method of identifying a cancer as responsive to immune checkpoint blockade (ICB)’ is not limiting because the body of the claim describes a complete invention and the language recited solely in the preamble does not provide any distinct definition of any of the claimed invention’s limitations. Thus, the preamble of the claim(s) is not considered a limitation and is of no significance to claim construction. See Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See MPEP § 2111.02.
In response to 2 above, the rejections above have been updated appropriately to meet the limitations of the instant claim set (see above for details).
Applicant arguments have been thoroughly reviewed but are not persuasive. The rejection(s) of claim(s) 1-5 and 12-16 is/are maintained.
Claim Rejections - 35 USC § 103
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.
Claim(s) 7-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0307868 A1 (hereinafter “US868”) as evidenced by Francisco et al. (Immunogenetics (2015) 67:651–663; hereinafter “Francisco”) as applied to claim(s) 1 above, and further in view of US 2007/0055049 A1 (hereinafter “US049”).
The teachings of US868 as recited above apply for claim 1.
Regarding instant claim(s) 7-11, US868 further teaches commonly expressed HLA alleles include HLA-B alleles [e.g., ¶ 0612; tables 1-2].
US868 does not expressly teach that the subject expresses HLA-B supertype (1) B44 and the radical substitution consists of glutamic acid, and/or (2) B27 and the radical substitution is histidine, lysine, or arginine.
Regarding instant claim(s) 7, 9-10, US049 teaches pulsed dendritic cells/APCs, HLA binding motifs, peptides, and their uses in cancer therapy and/or diagnosis [e.g., title; abstract; ¶ 0013, 0089, 0113, 0346, 0958-0959, 0961, 0987, 1000, 1026-1027]. US049 teaches that because human population groups have distinct patterns of distribution of specific HLA alleles and it is important to identify peptides capable of interacting with and/or across alleles to achieve sufficient coverage of all population groups [e.g., ¶ 0025]. US049 further teaches the invention defines positions within a motif enabling the selectin of peptides that will bind efficiently to HLA-B alleles; that the peptides are 9 residues (e.g., nonamers); that the HLA-B supertype is B44; and that the HLA-B44 supermotif is characterized by the presence of a negatively charged glutamic acid or aspartic acid residue in position 2 of the peptide ligands (e.g., a neoantigen) [e.g., ¶ 0089, 0091, 0113, 0046]. Regarding instant claim(s) 8, 11, US049 further teaches that the HLA-B supertype is B27, and that the HLA-B27 supermotif is characterized by the presence of a positively charge histidine, lysine, or arginine residue in position 2 of the peptide ligands (e.g., a neoantigen) [e.g., ¶ 0445, 0948].
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to substitute the HLA-B allele expressing APCs within the method of treating cancer comprising administration of dendritic cells pulsed with neoantigen as taught by US868, with the HLA-B44 and/or HLA-B27 supertype expression by APCs as taught by US049, to arrive at a method of treating cancer comprising administering neoepitope pulsed APCs and a PD1 inhibitor to a subject, wherein the subject expresses HLA supertype B44 and/or B27. A PHOSITA would have been motivated to modify the HLA-B allele expressing APCs within the method of treating cancer comprising administration of dendritic cells pulsed with neoantigen as taught by US868, to include the HLA-B44 and/or HLA-B27 supertype expression by APCs as taught by US049, because US868 teaches the base method of administering APCs pulsed with neoantigen for cancer therapy and that HLA-B alleles are commonly expressed, US868 and US049 both teach peptide antigen pulsed APCs for cancer therapy and HLA-B expression, and US049 teaches specific HLA-B supertype (e.g., B44 and/or B27) expression for cancer therapy. A PHOSITA would have been further motivated by US049 teaching that HLA alleles differ across populations and that including more alleles is necessary to cover more patient populations. There would have been a reasonable expectation of success for a PHOSITA to modify the HLA-B allele expressing APCs within the method of treating cancer comprising administration of dendritic cells pulsed with neoantigen as taught by US868, to include the HLA-B44 and/or HLA-B27 supertype expression by APCs as taught by US049, because US868 teaches base method of administering APCs pulsed with neoantigen for cancer therapy and that HLA-B alleles are commonly expressed, US868 and US049 both teach peptide antigen pulsed APCs for cancer therapy and HLA-B expression, and US049 teaches specific HLA-B supertype (e.g., B44 and/or B27) expression for cancer therapy. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0307868 A1 (hereinafter “US868”) as evidenced by Francisco et al. (Immunogenetics (2015) 67:651–663; hereinafter “Francisco”) as applied to claim(s) 1 and 4 above, and further in view of Richters et al. (Genome Medicine, (2019) 11:56; hereinafter “Richters”).
The teachings of US868 as recited above apply for claims 1 and 4.
US868 does not expressly teach that the biological sample is ctDNA.
Regarding instant claim(s) 15, Richters teaches best practices for characterization of neoantigens for clinical utility [e.g., title; abstract]. Richters further teaches that neoantigens are identified from a ctDNA biological sample [e.g., pg. 3, col. 2, ¶ 1].
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to substitute the biological sample in the method of treating cancer comprising administration of dendritic cells pulsed with neoantigen as taught by US868, with the ctDNA biological sample as taught by Richters, in the context of designing and developing a neoantigen based cancer therapy that doesn’t require invasive solid tumor biopsies. A PHOSITA would have been motivated to substitute the biological sample in the method of treating cancer comprising administration of dendritic cells pulsed with neoantigen as taught by US868, with the ctDNA biological sample as taught by Richters, because US868 teaches the therapeutic method and Richters teaches best practices for neoantigen characterization, including the use of ctDNA biological samples. There would have been a reasonable expectation of success for a PHOSITA to substitute the biological sample in the method of treating cancer comprising administration of dendritic cells pulsed with neoantigen as taught by US868, with the ctDNA biological sample as taught by Richters, because US868 teaches the therapeutic method and Richters teaches best practices for neoantigen characterization and a ctDNA biological sample. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant argues, in summary:
US868, US049, and/or Richters in combination fail to teach or suggest all elements of Applicant’s claims.
To the extent the Office can envision a motivation to combine the 2007 reference with the much-later filed 2019 reference, the Office has failed to establish that one skilled in the art would have done so with a reasonable expectation of success.
Instant invention addresses unmet need: surprising discovery that tumors harboring motif neoepitopes have greater expression of certain immune checkpoints that have been recognized to play a role in immune-escape (applicant provided specific examples).
Prior art doesn’t teach or suggest invention: does not teach that radical substitution in the 2nd position of a neoepitope enhances efficacy of ICB cancer therapy as it was not known that this could explain why some cancers respond to ICB while others do not.
Further Data: NCT03546361 preliminary data confirm enhanced immunogenicity of motif neoepitopes (provided numerous examples).
In response to 1 above, no specific examples of failing to meet the limitations of the claims is provided, therefore Applicant is considered to be referring the new limitations of the amended claim set. Briefly, new rejections are provided above that meet the limitations of the instant claim set (see rejections above for details).
In response to 2 above, applicant's argument based upon the age of the references, contentions that one reference is older than another reference are not impressive absent a showing that the art tried and failed to solve the same problem notwithstanding its presumed knowledge of the references. See In re Wright, 569 F.2d 1124, 193 USPQ 332 (CCPA 1977). For clarity of the record, the only 103 rejections employing US049 (e.g., the reference from 2005) are of claims 7-11, and therefore the argument is considered to pertain thereto. Briefly, regarding claims of no expectation of success, Briefly the reasonable expectation of success was based on US868 teaching the base method of administering APCs pulsed with neoepitope for cancer therapy and US049 teachings specifically of HLA-B supertype (e.g., B44 and/or B27) APCs pulsed with neoantigen as an effective cancer therapy (see above for details), which is consistent with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
In response to 3-5 above, arguments that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., greater expression of certain checkpoints, enhancing ICB efficacy in cancer) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
In response to 4-5 above, the active steps of the method are taught in the prior art (see rejections above for details). Applicant is advised that per MPEP 2112(I) provides “…[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999)….”
Applicant arguments have been thoroughly reviewed but are not persuasive. The rejection(s) of claim(s) 7-11 and 15 is/are maintained.
Conclusion
No claims are currently allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M CHATTIN whose telephone number is (571)270-0646. The examiner can normally be reached T-F 0600-1600 PST.
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/AMY M. CHATTIN/Examiner, Art Unit 1643
/GARY B NICKOL/Primary Examiner, Art Unit 1643
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