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 10Apr2026 is acknowledged in which claim(s) 1-25, 27-33, 37-43 were canceled, and claim(s) 44-52 are new.
Applicant’s election, with traverse, of Group 2, and further election of the species (1) “neoantigenic peptide: the aberrant fusion transcription factor encoded by EWSRJ-FLJJ, including the sequences listed in Table 8 (SEQ ID NO: 168, 172, 173, 175, 177-180, 186-190, 198 and 200)” and (2) “cancer: Ewin sarcoma” in the reply filed on 26Nov2025 is acknowledged.
No claim(s) are withdrawn from further consideration (because claim(s) directed to the non-elected invention were canceled by Applicant, see above) pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 26Nov2025.
Claim(s) 26, 34-36, and 44-52 is/are presented for examination on the merits.
Response to Amendment and Arguments
The objection(s) to the specification have been withdrawn in view of the Amendment filed on 10Apr2026.
All previous rejections of claim(s) 21-24, 30-31, 38 are moot in view of claim cancelation.
The rejection(s) of claim(s) 26, 34-36 under 35 U.S.C. § 101, of claim(s) 26, 34-36 under 35 U.S.C. § 112(b), of claim(s) 26, 34-36 under 35 U.S.C. § 102, and of claim(s) 23-24 under 35 U.S.C. § 102/103 have been withdrawn in view of the recent claim amendment filed on 10Apr2026, which added new limitations not previously considered, necessitating new rejection(s) and/or objection(s).
As all previously presented rejection(s) and/or objection(s) have been withdrawn, only those Applicant arguments pertinent to new rejection(s) and/or objection(s) are addressed herein.
New Rejections and/or Objections Necessitated by Claim Amendments
Claim Interpretation
Regarding claim(s) 26, 34-36, 44-52, recite(s) the phrase " the neotranscript expression is regulated by a transcription factor fusion as evidenced by expression in a cell line wherein the expression of said transcription factor fusion is made inducible," in line(s) 8-10 of claim(s) 26. The broadest reasonable interpretation is considered to encompass a neotranscript expressed in a cancer cell line (e.g., made inducible by the TF fusion of the cancer cell) and not expression in a normal cell line (e.g., not expressed in the absence of the cancer associated TF fusion).
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) 26, 34-36, 50-52 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.
Regarding claim(s) 26, 34-36, 44-52, the phrase "optionally" in line(s) 18 of claim(s) 26 and line(s) 3 of claim(s) 36 renders the claim(s) indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(h)(II). It is unclear if the limitation(s) following the phrase are limitation(s) or merely provided as an example. For the purposes of compact prosecution, the limitations following the phrase are not considered part of the claimed invention. This rejection may be overcome by amending claim(s) 26 and 36 to remove “optional” limitations and/or the phrase “optionally”. Claim(s) 34-35, and 44-52 can overcome this rejection by amending claim(s) 26 as recited above.
Claim(s) 50-52, recite(s) “the binding motif involved in promoter regulation is histone marks activation” in line(s) 1-2 of claim 50; and recite(s) “the binding motif involved in promoter regulation is a poly GGAA and histone marks activation” in line(s) 1-2 of claim 52, rendering the claim(s) indefinite. The instant disclosure dose not define “histone marks activation”. A skilled artisan would understand that active (e.g., accessible) histone markers include H3K4me3 and H3K27ac, but that these are commonly known in the art as epigenetic markers (e.g., post-translational modification(s) of histone protein(s)) which are not in themselves not considered a “binding motif”. Rather, a “binding motif” is a specific recurring sequence of DNA. Specifically, it is unclear if the phrase “histone marks activation” in each of claim(s) 50 and 52 means (1) a histone activation marker is associated with the ORF sequence; (2) a histone activation marker physically associates with a reader (e.g., bromodomains, chromodomains, Tudor domains) that recruits transcription machinery; or (4) something else. For the purposes of compact prosecution, the phrase will be considered to mean that ORF is associated with a histone activation marker. This rejection may be overcome by amending claim(s) 50, and 52 as recited above or to otherwise clearly recite the limitation(s) of the instant invention. Claim(s) 51 can overcome this rejection by amending claim(s) 50 as recited above.
Claim(s) 51, recite(s) “involved in promoter regulation is H3K27ac and H3K4me3 histone” in line(s) 1-2, rendering the claim(s) indefinite. The instant disclosure teaches markers of histone activation include H3K27ac and/or H3K4me3 histone marks, meaning that the recited markers can occur separately or together (e.g., both are not required to be markers of histone activation). Further the claim states “involved in promoter regulation is”, which is singular, but then recites 2 histone markers joined by an “and” (e.g., plural). Specifically, it is unclear if the phrase means the binding motif involved in promoter regulation comprises (1) H3K27ac and H3K4me3; (2) H3K27ac only; (3) H3K4me3 only; or (4) something else. For the purposes of compact prosecution, the phrase will be considered to mean “H3K27ac and/or H3K4me3”. This rejection may be overcome by amending claim(s) 51 as recited above or to otherwise 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) 26, 34-36, 44-45, 47, and 49-52 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2019/0030147 A1 (hereinafter “US147”), as evidenced by the instant specification.
Regarding instant claim(s) 26, 44-45, US147 teaches fusion-specific neoantigen cancer vaccines, and/or constructing de novo therapeutic fusion-specific neoantigen vaccines for patients with previously unidentified gene fusions [e.g., title, abstract; fig. 1]. US147 further teaches the cancer specific gene fusion EWS/FLI1 (same as EWSR1-FLI1) in particular is present in more than 85% of the Ewing’s sarcoma (e.g., fusion-driven) tumors [e.g., ¶ 0231, 0249-0250; tbls. 1, 10; example 9]. US147 further teaches embodiments wherein the neoantigen(s) selected is/are present in tumor and absent in normal tissues (e.g., expression in a cell line wherein the TF is made inducible, see claim interpretation above) [e.g., ¶ 0063, 0068, 0076]. US147 further teaches the fusion-derived peptides (e.g., fusion TF associated neoantigen peptides) is/are encoded by a part of an ORF [e.g., ¶ 0196], and that the neoantigen peptides comprise 8-10 amino acids [e.g., ¶ 0015]. US147 teaches vaccines comprise one or more fusion derived neoantigen peptides that induce T cell mediated antitumor responses [e.g., ¶ 0131, 0134, 0200]. US147 further teaches a vector comprising a polynucleotide that encodes the neoantigenic peptide [e.g., ¶ 0099, 0101, 0118, 0120, 0122].
Regarding instant claim(s) 34-35, US147 further teaches a method of treating cancer (e.g., Ewing sarcoma, see above) comprising administration of a vaccine comprising the fusion-specific neoantigen peptide (see above) to a subject in need thereof [e.g., abstract; ¶ 0016, 0018, 0024, 0038, 0041, 0060-0061, 0087-0124; figs. 1, 3]. US147 further teaches the vaccine may be composed of neoantigen peptide(s) or polynucleotide(s) encoding the neoantigen peptide(s) [e.g., ¶ 0216].
Regarding instant claim(s) 36, US147 further teaches the neoantigen fusion-specific vaccines may be administered in combination with another anti-cancer therapeutic agent such as chemotherapy and/or immunotherapy [e.g., ¶ 0125, 0129].
Regarding instant claim(s) 47, US147 further teaches that the fusion derived neoepitope(s) (e.g., neoantigen peptide(s)) can bind MHC Class I proteins and be recognized by T-cells [e.g., ¶ 0047].
Regarding instant claim(s) 49-52, EWS-FLI1 binds GGAA microsatellites in close vicinity to their TSS (<5Kb) and this binding is associated with the presence of H3K27ac and H3K4me3 activation marks, as evidenced by the instant specification [e.g., pg. 200, line(s) 24-26; pg. 210, line(s) 26].
Response to Arguments
Applicant argues that the fusion specific neoantigen of US147 and the instant invention are different classes of peptides. The claimed neoantigen peptides originate from de novo transcriptional activation of otherwise silent genomic regions, triggered by the gain-of function TF activity of the oncogenic fusion TFs. The claimed invention is based on the discovery that the chimeric transcription factors derived from tumor gene fusions have gain-of-function activates and have the ability to bind GGAA microsatellite sequences in the genome and activate corresponding genes and lead to transcriptional activation of otherwise transcriptionally silent genome regions. These tumor specific neoantigenic peptides correspond to peptides derived from these neotranscripts resulting from transcription activation by oncogenic chimeric transcription factors (i.e. transcripts derived from tumor-specific gene fusion) of otherwise transcriptionally silent genome regions. US147 only disclose transcripts or peptides derived directly from tumor-specific gene fusion and does not disclose a peptide encoded by an ORF sequence from a neotranscript, wherein its expression is regulated by a transcription factor fusion as evidenced by expression in a cell line wherein the expression of said transcription factor fusion is made inducible, specifically associated with the fusion-driven tumor type and encoded by a genome region having a binding motif involved in a promoter.
In response, as discussed in the rejections above, US147 is considered to teach all of the limitations of newly amended independent claim 26. Briefly, US147 teaches EWSR1-FLI1 fusion associated neoantigens present in Ewing Sarcoma subjects, wherein the fusion associated neoantigens are present in the cancer but not healthy cells, which is considered within the BRI of the instant claimed vaccine composition (see claim interpretation and rejections above for details). Additionally, for product by process claims, MPEP 2113(I) states “Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps” (e.g., not limited to “…as evidenced by…is made inducible…”, only to the composition). Further, Applicant is reminded that the discovery of a previously unknown property (e.g., gain-of-function arguments above) do not automatically mean something becomes patentable, see MPEP 2112(I). Lastly, based on Applicant disclosure, the argued points of difference relative to US147 (e.g., gain-of-function, GGAA binding, etc.) flow naturally from the function of EWSR1-FLI1 (see rejection above for details), per applicant’s own characterization [e.g., pg. 200, line(s) 24-26; pg. 210, line(s) 26].
Applicant arguments have been thoroughly reviewed but are not persuasive. The rejection(s) of claim(s) 26, 34-36, 44-45, 47, and 49-52 are maintained.
Claim Rejections - 35 USC § 102/103
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) 46, 48 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over US 2019/0030147 A1 (hereinafter “US147”).
The teachings of US147 as recited above apply for claim(s) 26.
Regarding instant claim(s) 46, 48, US147 is silent on the specific EWSR1-FLI1 encoded neoantigen sequence(s) of the instant claimed invention. However, US147 further teaches the de novo identification of novel/previously unknown neoantigens (e.g., of EWSR1-FLI1) [e.g., abstract; ¶ 0076, 0234; figs. 1-2] and therefore necessarily teaches the all possible naturally occurring neoantigens encoded by EWSR1-FLI1, including those of the instant claimed invention.
Response to Arguments
Applicant argues:
The present application is the first disclosure of the ability transcripts derived from TF gene fusions to transcriptionally activate silent genome regions to lead to neotranscripts. More specifically, the Applicant has demonstrated gain-of-function activities, and the ability to bind GGAA microsatellite sequences in the genome and to recruit chromatin remodeling complexes and histone modifying enzymes, as well as transcriptional machinery, that creates neomorphic enhancer regions that can interact with neighboring promoters and activate corresponding genes and lead to TF activation of otherwise transcriptionally silent genome regions. Inventors demonstrated neotranscripts are translated to neoantigen peptides, presented by APCs and recognized by T cells. The inventors have demonstrated the existence of such neotranscripts across multiple fusion-driven cancers.
The finding is significant for identification of therapeutic targets. This mechanistic insight and its therapeutic application were not known or suggested in US147. Examiner failed to establish a prima facie case of obviousness because there is no teaching, suggestion, or motivation in US147 to arrive at the claimed invention (MPEP 2143). This rejection is without merit because the examiner appears to be relying on the common technical knowledge based on his statement that "necessarily teaches all possible naturally occurring neoantigens" without providing any evidence. It is never appropriate to rely solely on "common knowledge" in the art without evidentiary support in the record.
In response to “1” above, , Applicant is reminded that the discovery of a previously unknown property (e.g., gain-of-function arguments above) do not automatically mean something becomes patentable, see MPEP 2112(I). Lastly, based on Applicant disclosure, the argued points of difference relative to US147 (e.g., gain-of-function, GGAA binding, etc.) flow naturally from the function of EWSR1-FLI1 (see rejection above for details), per applicant’s own characterization [e.g., pg. 200, line(s) 24-26; pg. 210, line(s) 26]. See rejections above for additional details.
In response to “2” above, the previous 102/103 rejections were based upon the teachings of US147 for personalized neoantigen cancer vaccines, EWSR1-FLI1 associated neoantigens, methods, and compositions thereof (see rejections above, and Fig. 1 below for details). Further, the full statement in the previous office action was “However, US147 further teaches the de novo identification of novel/previously unknown neoantigens (e.g., of EWSR1-FLI1) [e.g., abstract; ¶ 0076, 0234; figs. 1-2] and therefore necessarily teaches the all possible naturally occurring neoantigens encoded by EWSR1-FLI1, including those of the instant claimed invention.”. Therefore, the previous rejection was not based on common knowledge, but on the methods and compositions disclosed by US147. Briefly, US147 is considered to necessarily teach all possible naturally occurring neoantigens because it teaches a genus of personalized cancer vaccines, and specifically includes methods for detecting/identifying neoantigens de novo (see above for details). The applicant may be the first to report the mechanisms as claimed above, however the claims are drawn to the composition.
PNG
media_image1.png
802
325
media_image1.png
Greyscale
Applicant arguments have been thoroughly reviewed but are not persuasive. The rejection(s) of claim(s) 46 and 48 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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at (571) 272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/AMY M. CHATTIN/Examiner, Art Unit 1643
/GARY B NICKOL/Primary Examiner, Art Unit 1643
Prosecution Insights