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
Claim(s) 20-43 is/are currently pending.
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.
Claims 20, 25, 27-29, 32-33, 37, and 39-43 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 26Nov2025.
Claim(s) 21-24, 26, 30-31, 34-36, and 38 is/are presented for examination on the merits.
Specification
The use of trade name(s) or mark(s) used in commerce (e.g., Applied Biosystems, Illumina, Opdivo, Keytruda, HyClone, Gibco, Macherey-Nagel, BioRad, Eurofins), has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (e.g., pg. 9, lines 27-30; pg. 18, line 22; pg. 21, lines 26-27; pg. 32, line 15; pg. 195, line 23; pg. 200, lines 12, 16). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Interpretation
Regarding Applicant election of “EWSRJ-FLJJ”, the art and the Applicant’s own disclosure do not teach a fusion TF of “EWSRJ-FLJJ”. However, the Applicant’s disclosure and claims teach a preferred fusion TF known as “EWSR1-FLI1”, which is known in the art. Therefore, for the purposes of compact prosecution, the Applicant’s election will be considered to mean “EWSR1-FLI1”.
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) 21-24, 26, 30-31, 34-36, and 38 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 claims 21 (and dependent claims 22-24, 26, 30-31, 34-36, 38), the phrase “(ORF)” is not defined in the terms preceding it. Thus, the phrase “(ORF)” renders the claim indefinite because it is unclear whether the limitation(s) in the parentheses are a part of the claimed invention. See MPEP 2173.05(d). It is unclear if “ORF” is a limitation or merely provided as an example. To promote compact prosecution, the phrase “ORF” is considered a limitation of the claim(s). This rejection may be overcome by amending claims 21 to properly define (ORF) in the terms preceding it. Dependent claims 22-24, 26, 30-31, 34-36, 38 can overcome this rejection by amending claim 21 as described above.
Regarding claim(s) 21 (and dependent claims 22-24, 26, 30-31, 34-36, 38), the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For the purposes of compact prosecution, the limitations following the phrase “such as” are not considered part of the claimed invention. This rejection may be overcome by amending claim 21 to remove “such as”. Dependent claims 22-24, 26, 30-31, 34-36, 38 can overcome this rejection by amending claim 21 as described above.
Regarding claim(s) 21 (and dependent claims 22-24, 26, 30-31, 34-36, 38), the phrases “its expression” in 21(i)(a), “it is specifically associated with” in 21(i)(b), and “it is are encoded by genome regions…motifs” in 21(i)(c) renders the claim unclear. Specifically, it is unclear if the “it(s)” of the above phrases refer to (1) the neoantigenic peptide, the ORF, the neotranscript, or something else. For the purposes of compact prosecution, the “it(s)” of the phrases above are considered to refer to the neotranscript of 21(i). Further, the “is are…regions…motifs” in 21(i)(c) is unclear because it is not apparent if the limitation requires more than one genome regions and/or binding motifs are required for a single neoantigenic peptide, or something else. For the purposes of compact prosecution, 21(i)(c) is considered to require one or more genome regions having one or more binding motifs. This rejection may be overcome by amending claim 21 as indicated in the compact prosecution statements above. Dependent claims 22-24, 26, 30-31, 34-36, 38 can overcome this rejection by amending claim 21 as described above.
Regarding claim(s) 21 (and dependent claims 22-24, 26, 30-31, 34-36, 38), the phrase “…fusion-driven tumor type, (C) it is are encoded…” renders the claim indefinite. Specifically, the lack of a joining word (e.g., “and”, “or”) makes it unclear if the claim requires 21(i)(a-c) or 21(i)(a, b, or c). For the purposes of compact prosecution, the joining word is considered to be “or” between 21(i)(b) and 21(i)(c). This rejection may be overcome by amending claim 21 to clearly recite the limitations of the claimed invention. Dependent claims 22-24, 26, 30-31, 34-36, 38 can overcome this rejection by amending claim 21 as described above.
Regarding claim(s) 21 (and dependent claims 22-24, 26, 30-31, 34-36, 38), the phrase “…located at 5kb or less of the TSS. (ii) is expressed…” renders the claim unclear. MPEP 608.01(m) provides “Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995).”. Specifically, the inclusion of a period in the body of a claim as well as at the end in addition to no joining word (e.g., “and”, “or”) makes it unclear if the limitations require 21(i)(a-c) only, 21(i)(a-c) and 21(ii), 21(i)(a-c) or 21(ii), or something else. For the purposes of compact prosecution, the period between 21(i)(c) and 21(ii) is considered to be “; or”. This rejection may be overcome by amending claim 21 as recited above. Dependent claims 22-24, 26, 30-31, 34-36, 38 can overcome this rejection by amending claim 21 as described above.
Regarding claim(s) 21 (and dependent claims 22, 24, 26, 30-31, 34-36, 38), 23, the phrase “a part of an (ORF) sequence” (claim 21) or “a part of an open reading frame (ORF)” (claim 23) renders the claims indefinite. Further, the claims and the specification do not provide a definition for “a part of” an ORF and therefore it is unclear what would meet the limitations following the phrase “a part of”. Specifically, it is unclear if “a part of” means (1) 1 residue, (2) 3 residues, (3) the entire ORF, or something else. For the purposes of compact prosecution, the teaching of any ORF in association with a neoantigen transcript and/or peptide will be considered to meet the limitations of “a part of” an ORF. This rejection may be overcome by amending claims 21 and 23 to (1) clearly define the meaning of “a part of” or (2) remove “a part of”. Dependent claims 22, 24, 26, 30-31, 34-36, 38 can overcome this rejection by amending claim 21 as described above.
Regarding claim(s) 22, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). . For the purposes of compact prosecution, the limitations following the phrase “such as” are not considered part of the claimed invention. This rejection may be overcome by amending claim 22 to remove the phrase “such as”.
Claim(s) 23, is/are rejected for making reference to tables within the specification and/or figure(s). Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim.” See MPEP 2173.05(s). This rejection may be overcome by amending claim 23 to remove references to figure(s).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim(s) 21-24, 26, 30, 34-36, and 38 is/are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature (natural phenomenon) without significantly more.
Claims 21 (and dependent claims 22-24, 26, 30, 34-36, 38), are evaluated using the “Subject Matter Eligibility Test for Products and Processes” flow chart as shown in MPEP § 2106 (III).
Step 1: Is the claim to a process, machine, manufacture or composition of matter?
Yes. The claim is drawn to a composition of matter which is one of the four statutory categories.
Step 2A, Prong One: Does the claim recite an abstract idea, law of nature, or natural phenomenon?
Yes. The claims are directed towards the natural phenomenon “a tumor specific neoantigenic peptide”. In the broadest reasonable interpretation of the tumor specific neoantigenic peptide in any of the ways recited above comprise a natural product (e.g., the neoantigen is endogenous because cancer cells produce the neoantigen natural product).
Step 2A, Prong Two: Does the claim recite additional elements that integrate the judicial exception into a practical application?
No. While claim 21 recites “wherein said tumor is associated with a transcription factor fusion, and wherein said peptide (i) is encoded by a part of an ORF sequence from a neotranscript…(ii) Is expressed at a higher level or frequency in a sample from said tumor compared to a normal tissue sample”, these do not integrate the judicial exception into a practical application. Specifically, describing a naturally occurring phenomenon (e.g., neoantigens associated with specific tumor(s), specific TF fusions, and/or relative frequence in tumor vs. non-tumor samples) is not a practical application, but rather are generally linking the judicial exception to a particular technological environment or field of use (see MPEP § 2106.05(h)).
Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
No. The judicial exception is recited without additional limitations amounting to significantly more than the exception. While a composition comprising a specific neoantigenic peptide is claimed, the neoantigenic peptide(s) is/are considered to be the same neoantigen(s) that would be unchanged if isolated from a cancer subject (e.g., a product of nature). Thus, there is no change in functional activity of the compositions. No additional elements are present outside of the naturally occurring product of nature in the instant claimed composition(s) and, therefore, do not amount to significantly more than the judicial exception that is claimed.
Claim(s) 22-24, 26, 30, which depend from claim 21, act to further limit the (1) aberrant fusion TF, (2) the ORF sequence(s), (3) neoantigenic peptide sequence, (4) immunogenic composition, (5) a polynucleotide encoding the neoantigen. The limitations do not amount to significantly more than the judicial exception.
Claim(s) 34-36, 38, which require the composition of claim(s) 21 (claims 34-35. 38), 34 (claim 35), and/or claim 30 (claim 38), act to further limit independent claim 21 by using the neoantigen composition thereof in the treatment of cancer. However, as the Applicant disclosure indicates, the neoantigens are produced by the specific tumors having specific fusion TFs [e.g., pg. 196, “Tumor RNA-seq used for discovery of neogenes”; pg. 201, lines 28-32-pg. 202, lines 1-15] and therefore the neoantigens (peptide or polynucleotide) are considered a product of nature. Further, regarding claim 36, the Applicant disclosure indicates that the combination therapy may include “vaccines or immunogenic compositions comprising polynucleotide encoding the peptides” [e.g., pg. 50, lines 16-22]. As the neoantigens (peptides and/or polynucleotides) are found naturally occurring in a subject (e.g., a cancer patient) the neoantigens would have necessarily been presented by the natural immune system (e.g., by antigen presenting cells) as a method to kill cancer cells, as was previously known and described in the art by Ward et al. (Adv Immunol. 2016, 130:25-74; abstract and 2.1). Therefore, the limitations do not amount to significantly more than the judicial exception.
As the instant claims 21-24, 26, 30, 34-36, 38 recite judicial exceptions for which the judicial exception is not integrated into a practical application, and no elements that amount to significantly more than the judicial exception are recited, the claims were found not to be drawn to eligible subject matter under 35 USC § 101.
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) 21-22, 26, 30-31, 34-36, and 38 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2019/0030147 A1 (hereinafter “US147”).
Regarding instant claim(s) 21-22, US147 teaches fusion-specific neoantigen cancer vaccines, and/or constructing de novo therapeutic fusion-specific neoantigen vaccines for patients that previously unidentified gene fusions [e.g., title, abstract; fig. 1]. US147 further teaches cancer specific gene fusions have been used as neoantigens in several anti-cancer vaccines, that the EWS/FLI1 (same as EWSR1-FLI1) fusion 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., ¶ 0063, 0068, 0076]. US147 further teaches the fusion-derived peptides (e.g., fusion TF encoded) is encoded by a part of an ORF [e.g., ¶ 0196].
Regarding instant claim(s) 26, US147 further teaches that the fusion derived neoepitope(s) (of the neoantigen peptide vaccine above) can bind HLA proteins and be recognized by T-cells [e.g., ¶ 0047]. US147 teaches vaccines comprise one or more fusion derived neoantigen peptides that induce T cell mediated antitumor responses [e.g., ¶ 0131, 0134, 0200].
Regarding instant claim(s) 30-31, 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, 38, US147 further teaches a method of treating cancer (e.g., Ewing sarcoma, see above) comprising administration of a vaccine comprising the fusion-specific neoantigenic peptide 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].
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) 23-24 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 21.
Regarding instant claim(s) 23-24, 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.
Conclusion
No claims are currently allowed.
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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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.
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/AMY M. CHATTIN/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643