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 .
Claim 113 has been canceled. Claim 92, 95, 104-107, 110, 118-120, 126 and 127 have been amended. Claims 128 and 129 have been added. Claims 92-112, 114-129 are pending and under consideration.
The rejection of claims 92-112, 114-129 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in light of applicant’s amendments..
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 128 and 129 are rejected and claims 92-119, and 121-127 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is maintained for reasons of record. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 92-112 and 114-119 are drawn to a genus of RNA vaccines for treating cancer in a patient comprising an ORF encoding peptide epitopes selected by identification of neoepitopes that are expressed in a tumor sample of a patient but not in normal tissue of the patient, wherein the epitopes are selected which lack self-reactivity, comprise at least one mutation that is a insertion, deletion, substitution or frameshift, and wherein the epitopes include at least one MHC I epitope and at least one MHC II epitope. Claims 121-127 are method claims reliant on the genus of the aforesaid mRNA vaccines. The specification lacks an adequate written description of the genus because the genus is highly variant due to the unique nature of the cancer mutanome in individual patients requiring “personalization” of the genus (Sahin and Tureci, Science, March 2018, Vol. 359, 6 pages, reference of the IDS filed 9/24/2021, see page 1, third column, lines 1-6 of the bottom paragraph). One of skill in the art could not envisage the neoepitopes produced in the patients tumor because the accumulation of mutations within a tumor is governed by random events in the tumor microenvironment giving rise to “passenger” mutations in addition to “driver ,mutations” (Sahin and Tureci, page 1, first column, lines 1-13), and the resulting neoepitopes cannot be predicted. One of skill in the art would reasonably conclude that applicant was nor in possession of the genus of mRNA vaccines at the time of filing.
Applicant argues that there is no per se rule that an adequate written description of an invention that involves a biological macromolecule must contain a recitation of known structure. Applicant cites Falkner v Inglis (Fed Cir 2006). This has been considered but not found persuasive. In Falkner v Inglis the Cour concluded that publicly available information, such as published gene sequences, can satisfy the written description requirement without needing to be explicitly included in a patent application. In the instant case, the prior art cannot be relied upon to describe the neoepitopes produced in the patients tumor because the accumulation of mutations within a tumor is governed by random events in the tumor microenvironment giving rise to “passenger” mutations in addition to “driver mutations” which are specific to a patient.
Applicant argues that pages 28-30 of the disclosure provides evidence that applicant was in possession of nucleic acid cancer vaccines comprising one or more nucleic acids, wherein each of the nucleic acids encodes at least one suitable cancer antigen specific for cancer in a subject. This has been considered but not found persuasive. Simply stating the intention of the application does not provide for an adequate written description of a personalized mRNA cancer vaccine for treating cancer in a patient, or a genus of personalized mRNA cancer vaccines for treating cancer in a genus of patients, because one of skill in the art cannot envisage the neoepitopes produced in the patients tumor because the accumulation of mutations within a tumor is governed by random events in the tumor microenvironment giving rise to “passenger” mutations in addition to “driver mutations”.
Applicant argues that the product-by-process language to recite the peptide epitopes which is a mechanism for claiming subject matter where the product can only be defined by the process steps by which it is made. Applicant states that because it is not possible to prospectively know the amino acid sequences of the specific neoepitopes that will be present in a given patient. This has been considered but not found persuasive. Claim 92 provides multiple steps for selecting peptide epitopes which are unique to specific patient’s tumor. It is noted that the selection process provides for a wide range of variability, such that each selected peptide contains at least one of an insertion, deletion substitution or frameshift mutation. Thus, a routineer can select different peptide epitopes based on “at least one” of the listed mutation alternatives. Also, a rotineer can select different epitopes based on requirement that at least one peptide epitope which is a class I epitope and at least one epitope is a class II epitope. Following the instructions of the claim can produce a wide range of mRNA vaccines from a single tumor sample of a patient. Thus, the epitope selecting process requires subjective selecting carried out by one of skill in the art, and can produce a genus of mRNA vaccines rather than a single product made by a particular process.
The rejection of claims 92-107, 109-112 and 114-127 under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Valiante et al (WO2018/144082, reference of the IDS filed 9/24/2021) is withdrawn in light of applicant’s amendments of claim 92 and 120 requiring that the hotspot mutations were selected from a BRAF mutation, a IL3CA mutation, a EGFR mutation , a FGFR3 mutation, an erB2 mutation , a PTEN mutation and a BCOR mutation.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 92-112 and 114-129 are rejected under 35 U.S.C. 103 as being unpatentable over Valiante et al (WO2018/144082) in view of the abstract of Starostik et al (Journal of Molecular Diagnostics, 2013, Vol. 15, No. 6, p. 932, abstract no. TT2525) and Angel et al (WO2014/071219).
Claim 92 is drawn to a personalized mRNA cancer vaccine for treating cancer in a patient comprising (i) a mRNA comprising an ORF encoding 5-50 peptide epitopes in head-to-tail order connected directly or by a linker, wherein the mRNA includes a N1-methylpseudouridine, and (ii) a lipid nanoparticle comprising 20-60% ionizable cationic lipid, 5-25% non-cationic lipid, 25-55% sterol and 0.15-15% PEG-modified lipid,
wherein the epitopes are selected by (a) identifying neoepitopes expressed in the tumor but not the normal tissue of the patient, (b) determining whether the identified neoepitopes include one or more neoepitopes comprising a cancer hotspot mutation selected from BRAF, PIK3CA, EGFR, FGFR3, ErbB2, PTEN and BCOR and (c) selecting the peptides to be included as the corresponding mRNA ORF based on:
peptide epitopes comprising the identified neoepitopes
lack of “self-reactivity”
peptide epitopes comprise at least one insertion, deletion substitution or frameshift mutation, and
peptide epitopes comprise a at least one MHC I epitope and at least one MHC II epitope,
wherein if the identified neoepitopes include a cancer hotspot mutation selected, in part, from a KRAS or NRAS mutations, said epitopes are selected from the identified neoepitopes comprising the cancer hotspot mutation.
Claim 93 requires that the ORF of claim 92 encodes 20-35 epitopes.
Claim 94 requires that one or more of the selected neoepitopes of claim 92 are from the one or more cancer hotspot mutations.
Claim 96 requires that at least 30% of the peptide epitopes of claim 92 are MHC I.
Claim 97 specifies that the identifying of neoepitopes in claim 92 comprises identifying a patient specific mutanome by analyzing a transcriptome and an exome of the patient.
Claim 98 specifies that each of the epitopes in claim 92 has a length of 8-29 amino acids.
Claims 99 and 100 require that at least two of the epitopes are connected by a linker and without a linker, respectively.
Claim 101 specifies that the mRNA of claim 92 further comprises a one or more feature selected from a 5’ UTR, a 3’UTR, a poly-A tail and a cap structure.
Claim 102 requires that the mRNA of claim 92 is fully modified with N1-methylpseudouridine.
Claim 103 requires that the ORF encodes 34 epitopes.
Claims 104-106 require that in claim 92 the ratio of MHC I epitopes to MHC II epitopes is at least 2:1, 3:1 and 5:1, respectively.
Claim 107 specifies that the epitopes of claim 92 comprise 8-29 amino acids and include one or more SNP.
Claim 108 requires that the ORF encodes 34 epitopes comprising 29 MHC I epitopes and 5 MHC II epitopes.
Claim 109 specifies that the ORF encodes 5-40 epitopes.
Claim 110 requires, in part, that (b) one or more epitopes of claim 92 exhibits T cell reactivity.
Claim 111 requires that the peptide epitopes of claim 92 are arranged to minimize pseudo-epitopes.
Claim 112 requires that at least one or the epitopes of claim 92 is a predicted T cell reactive epitope.
Claim 114 specifies that the one or more epitopes of claim 92 comprise a centrally located SNP.
Claim 115 specifies that the ionizable cationic lipid of claim 92 comprises Formula (I).
Claim 116 requires that the ionizable cationic lipid of claim 115 comprises specifically compound 1.
Claim 117 requires that the mRNA of claim 116 encodes a total protein length of 100-1000 amino acids.
Claim 118 requires that the selecting of epitopes on claim 92 is based on a weighted value assigned to individual neoepitope properties selected, in part, from (i) lack of self-reactivity; (ii) type of mutation in the neoepitope; (iii) abundance of a mutation present in a plurality of neoepitopes; and (v) presence of a conserved amino acid or a non-conserved amino acid within the neoepitope.
Claim 119 requires that each peptide epitope in claim 92 is of equal length.
Claim 120 is drawn to a method of making the mRNA cancer vaccine of claim 92 comprising a mRNA comprising an ORF encoding 5-50 peptide epitopes in head-to-tail order, wherein the mRNA includes a N1-methylpseudouridine, and (ii) a lipid nanoparticle comprising 20-60% ionizable cationic lipid, 5-25% non-cationic lipid, 25-55% sterol and 0.15-15% PEG-modified lipid,
wherein the epitopes are selected by (a) identifying neoepitopes expressed in the tumor but not the normal tissue of the patient, (b) determining whether the identified neoepitopes include one or more neoepitopes comprising a cancer hotspot mutation selected from BRAF, PIK3CA, EGFR, FGFR3, ErbB2, PTEN and BCOR and (c) selecting the peptides to be included as the corresponding mRNA ORF based on:
peptide epitopes comprising the identified neoepitopes
lack of “self-reactivity”
peptide epitopes comprise at least one insertion, deletion substitution or frameshift mutation, and
peptide epitopes comprise a at least one MHC I epitope and at least one MHC II epitope,
wherein if the identified neoepitopes include a cancer hotspot mutation selected, in part, from a BRAF, PIK3CA, EGFR, FGFR3, ErbB2, PTEN or BCOR mutations, said epitopes are selected from the identified neoepitopes comprising the cancer hotspot mutation, and (d) preparing the mRNA having an ORF encoding 5-50 selected peptide epitopes, wherein the mRNA comprises N1-methylpseudouridine and (e) preparing the personalized mRNA vaccine comprising the mRNA and the lipid nanoparticle..
Claim 121 is drawn to a method for treating a patient having cancer comprising administering an effective dosage of the vaccine of claim 192. Claim 122 specifies that the administration in claim 121 is intramuscular administration. Claim 123 requires that the cancer of claim 121 is selected from non-small cell and small cell lung cancers, melanoma, bladder urothelial carcinoma, HPV-negative head and neck squamous cell carcinoma (HNSCC), and a solid malignancy that is microsatellite high (MSI H) / mismatch repair (MMR) deficient renal cancer and gastric cancer. Claim 124 specifies that the cancer of claim 123 is NSCLC that lacks an EGFR sensitizing mutation and/or an ALK translocation. Claim 125 requires that the cancer is a solid malignancy that is microsatellite high (MSI H) / mismatch repair (MMR) deficient selected from colorectal cancer, stomach adenocarcinoma, esophageal adenocarcinoma, and endometrial cancer.
Claim 126 requires the further administration of an anti-PD-1 antibody to the patient in the method of claim 126. Claim 127 specifies that the anti-PD-1 antibody is pembrolizumab.
Valiante et al (WO2018/144082) disclose an RNA cancer vaccine comprising one or more mRNA each having one or more reading frames encoding 45-55 peptide epitopes which are personalized cancer antigens, wherein at least one of the peptide epitopes is an activating oncogene mutation peptide, and wherein the vaccine is formulated in a lipid nanoparticle (claim 33 of ‘082). Valiante et al disclose that personalized cancer antigens include neoepitopes (page 26, lines 28-30). Valiante et al disclose an embodiment wherein the one or more mRNAs encode 48-54 personalized cancer antigens (claim 34 of ‘082) which meets the limitation of 5-50 peptide epitopes in claims 92 and 120 and 5-40 peptide epitopes in claim 109. Valiante et al disclose that in a separate embodiment that the mRNA comprises a concatemer wherein in the mRNA encoding each peptide epitope is interspersed by cleavage sensitive sites (claim 38a), which meets the limitation of arranged in a head-to-tail formation in claim 92 and 120; are linked directly to one another without a linker (claim 38b) or are linked to one another by a single nucleotide linker (claim 38c), which meets the limitation of claim 99 for connection via a linker, claim 100 for connection without a linker; comprise 25-35 amino acids including a centrally located SNP (claim 38d), which meets the limitation of claims 93, 103 and 114, 50% of the peptides have a have a predicated binding affinity of >500nM for HLA-A, -B and/or DRB1 (claim 38g), which meets the limitation of claim110(a); 50% of the epitopes have a binding affinity for MHC I (claim 38j), or 50% of the epitopes have a binding affinity for MHC II (claim 38k) which meets the same limitation in claims 92(iv), 102(iv) and 96; the mRNA encodes peptides in an order which minimizes pseudo-epitopes (claim 38k), which meets the limitations of claim 111.
Valiante et al disclose that the activating oncogene mutation of is H-RAS or K-RAS, wherein the KRAS mutation is G12D, G12V, G12S, G12C, G12A, G12R or G13D (claim 55) which meets the limitation of instant claims 92 and 120 for a KRAS mutation or a NRAS mutation, claim 94 for inclusion of the cancer hotspot mutation and claim 95 for a KRAS mutation selected from a G12 or a G13 mutation.
Valiante et al disclose that the lipid nanoparticle has a molar ratio of about 20-60% cationic amino lipid; 5-25% neutral lipid; 25-55% sterol and 0.5-15% PEG-modified lipid (claim 86) which meets that same limitation in claims 92 and 120. Valiante et al disclose the cationic amino lipid of Formula I(page 187) and compound 25 (page 215) which meet the limitations of claims 115 and 116.
Valiante et al disclose a method of identifying a set of neoepitopes for use in a personalized mRNA cancer vaccine comprising identifying a patient specific mutanome by analyzing a patient transcriptome and a patient exome, which meets the limitation of claim 97; and (b) selecting a subset of 15-500 neoepitopes from the mutanome using a weighted values based on at least three criterion including conservative vs non-conservative amino acid substitution, which meets the limitation of a substitution in claims 92(iii), 118(v), and 120(iii); selfness, which meets the limitation of lack of self-reactivity in claims 92(ii, 118(i) and 120(ii); promiscuity score, which meets the limitation of MHC binding capacity in claim 118(iv); class I vs class II proportion, which meets the limitation of claims 92(iv) and 120(iv); proportion of point mutations versus complex epitopes which meets the limitations of claim 92(iii), 118(ii) and 120(iii) for a substitution or a frameshift; and abundance of RNA seq reads, which meets the limitation of claim 113 and 118(iii) for a mutation abundant in the sample (page 20, lines 3-23). Valiante et al disclose that the mRNA cancer vaccine include at least 2 cancer antigens including mutation selected from frame-shift and recombinations of any of point mutations, read-through mutations, splice site mutations, chromosomal rearrangements resulting in gene fusions, and deletions (page 35, lines 21-31). Valiante et al disclose that at least one of the peptide epitopes is a T cell epitope (claim 76 of ‘082) which meets the limitation of claim 112. Valiante et al disclose an embodiment wherein at least 30% of the epitopes have a highest affinity for MHCI or 30% of the peptides have a highest affinity for MHCII claim 38e and f), and that I some embodiments the ratio of MHCI epitopes to MHCII epitopes is 3:1 which meets the limitations of claim 105; and the ratio of MHCI epitopes to MHCII epitopes is selected from about 70% which meets the limitations of claim 104 for “at least 2:1” because 2:1 would be would be at 66%, and the ratio of MHCI epitopes to MHCII epitopes is selected from about 90% which meets the limitation of claim 106 for “at least 5:1” because 5:1 would be 83%.
Valiante et al disclose “52 mer constructs” and “20 mer constructs” (page 33, lines 25-26) which meet the limitation of 119 for each peptide epitope having an equal length. The 20mer constructs also meet the limitation of claim 98 for each peptide epitope having a length of 8-29 amino acids. Valiante et al disclose that the mRNA has a Nl- methylpseudouridine modification (claim 103) which meets the same limitation in claims 92 and 120, and that in some embodiments the mRNA is fully modified with Nl- methylpseudouridine (page 5, lines 20-23) which meets the requirement of claim 102. Valiante et al disclose that the mRNA comprises a 5’UTR, a poly-A tail and a 5’Cap 1 structure (page 5, lines 15-19) which meets the requirements of claim 101. Valiante et al disclose an embodiment wherein each epitope comprises 25-35 amino acids and includes a centrally located SNP (page 15, lines 32-33), which meets the imitations of claim 107, for epitopes comprising 25-29 amino acids.
Valiante et al disclose a method of vaccinating a subject comprising administering to a subject having cancer the inventive mRNA vaccine (claim 104), wherein the vaccine is administered by intramuscular injection (claim 110), and further comprising administering an additional cancer therapeutic (claim 111) which is pembrolizumab (claim 118) which meets the requirements of instant claims 121, 122, 126 and 127. Valiante et al disclose that the cancer includes cancer is selected from the group consisting of non-small cell lung cancer (NSCLC), small cell lung cancer, melanoma, bladder urothelial carcinoma, HPV-negative head and neck squamous cell carcinoma (HNSCC), and a solid malignancy that is microsatellite high (MSI H) / mismatch repair (MMR) deficient (page 14, lines 27-30), wherein the NSCLC lacks an EGFR sensitizing mutation and/or an ALK translocation (page 14, lines 30-31) which meets the limitations of claims 123 and 124. Valiante et al disclose that the solid malignancy is microsatellite high (MSI H) / mismatch repair (MMR) deficient and is colorectal cancer, stomach adenocarcinoma, esophageal adenocarcinoma, or endometrial cancer (page 14, lines 31-34) which meets the limitations of claim 125.
Valiante et al teach the activating oncogene mutation of is H-RAS or K-RAS. Valiante et al do not specifically teach the activating mutation is BRAF, EGFR,
The abstract of Starostik et al teaches that driver mutation that provide NSCLC tumor cells with selective growth advantage are located in the genes encoding proteins, selected from a group including BRAF, EGFR, ERBB2, PIK3CA and PTEN in addition to the HRAS and KRAS of Valiante et al. The abstract teaches the identification of point mutations within said proteins.
Angel et al teach that mutations in certain genes are associated with the cancerous state. Angel et al teach examples of such mutated genes include BRAF-V600, EGFR-L858, FGFR3-S249, PIK3CA-H1047 and PTEN-R130.
It would have been prima facie obvious at the time prior to the effective filing date to substitute mRNA encoding BRAF-V600, EGFR-L858, FGFR3-S249, PIK3CA-H1047 and/or PTEN-R130 for the KRAS-G12D, G12V and G13D taught by Valiante et al. One of skill in the art would have been motivated to dos o by the teachings of the abstract of Starostik that driver mutations in BRAF, EGFR, ERBB2, PIK3CA and/or PTEN were cancer associated equivalents of KRAS or NRAS, and the teachings of Angel et al identifying specific point mutations within said genes, identified as BRAF-V600, EGFR-L858, FGFR3-S249, PIK3CA-H1047 and/or PTEN-R130 associated with the cancerous state.
Regarding claim 108, Valiante et al do not specifically teach that the mRNA ORF encodes 34 epitopes comprising 29 MHC I epitopes and 5 MHC II epitopes.
Valiante et al teach an embodiment wherein each epitope comprises 25-35 amino acids and includes a centrally located SNP (page 15, lines 32-33). Thus, an epitope of 34 amino acids is taught by Valiante et al. Valiante et al teach an embodiment wherein about 80% or about 90% of the epitopes are MHCI, leaving about 20% to about 10% as MHC II (page 39, lines 7-8). For 34 peptide epitopes, this means that 28 to 31 peptide epitopes would be MHC I, and 6 to 3 peptide epitopes would be MHC II. Thus, a mRNA ORF encoding 29 MHC I peptide epitopes and 5 MHC II peptide epitopes are obvious over the teachings of Valiante et al.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
The provisional rejection of claims 92-96, 98-101, 103, 105, 109, 111, 115, and 116 are on the ground of nonstatutory double patenting as being unpatentable over claims 1, 11, 25, 26, 132, 133, 138, (141), 142-167 of copending Application No. 16/482,844(reference application) is withdrawn in light of applicant’s amendment in the instant application and the reference application.
Claims 128 and 129 are provisionally rejected and claims 92-96, 99, 100, 103, 109, 111, 115, 116, 121, 123, 126 and 127 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5, 7, 10, 11, 18, 21, 23, 24, 26, 27, 28, 30, 31, 39, 57, 59, 68, 75 and 88 of copending Application No. 17/291,947 (reference application).. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘947 application anticipate, or render obvious, the instant claims.
Claims 1, 7, 10 and 85 anticipate claims 92-95 to the extent that the ORF encodes 5-50 epitopes which are the peptide epitopes of the cancer hotspot antigens of BRAF V600, PIK3CA R88, PIK3CA E545, PIK3CA H1047, EGFR L858, FGFR3 S249, erbB2 S310, PTEN R130 and BCOR N1459, wherein said hotspot antigens comprise a substitution as required in claim 92(iii). Claim 21 anticipates claim 92 in that the peptides are in a head-to-tail configuration. Claims 23 and 24 anticipate the same in claim 92, 99 and 100. Claim 27 anticipates instant claim 111. Claim 28 of the ‘947 application anticipates section (iv) of claim 92 and claim 96. Claims 30 and 31 and claim 88 anticipate the lipid nanoparticle of claim 92 comprising 20-60% ionizable cationic lipid, 5-25% non-cationic lipid, 25-55% sterol and 0.5-15% PEG modified lipid, as well as instant claims 115 and 116. Claims 39 and 57 anticipate the same in instant claim 121. Claim 84 anticipates instant claim 122. Claim 59 anticipates claim 123. Claims 75 and 83 anticipate instant claims 126 and 127.
Claims 18 and 86 teach that the mRNA comprises at least one chemical modification, but do not specify that the modification is N1-methylpseudouridine as required in claims 92.
Section 804IIb of the M.P.E.P. states
The specification can be used as a dictionary to learn the meaning of a term in the patent claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999).
In the instant case, the ‘949 application defines chemical modification as including: pseudouridine, N1-methylpseudouridine, N1-ethylpseudouridine, 2-thiouridine, 4′-thiouridine, 5-methylcytosine, 2-thio-1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine, 2-thio-dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine, 4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine, 4-thio-pseudouridine, 5-aza-uridine, dihydropseudouridine, 5-methyluridine, 5-methyluridine, 5-methoxyuridine, and 2′-O-methyl uridine.
Thus, the chemical modification of N1-methylpseudouridine required in claim 92 is obvious over claims 18 and 86 and the exemplary language of the specification.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant argues that the ‘947 application is later filed, and that the M.P.E.P. dictates that the rejection should be withdrawn if the rejection is the only one remaining. This is not persuasive due to the remaining rejections of record.
Claims 128 and 129 are provisionally rejected and claims 92-97, 99, 100, 103, 109, 111, 115, 116, 121, 123, 126 and 127 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5, 7, 10, 11, 18, 21, 23, 24, 26, 27, 28, 30, 31, 38, 39, 57, 59, 68, 75 and 88 of copending Application No. 17/291,947 in view of Sahin and Tureci (Science, March 2018, Vol. 359, pp. 1355-1360).
Instant claim 97 requires that the identification of the neoepitopes of claim 92 comprises identifying a patient specific mutanome by analyzing a transcriptome of the patient and an exome of the patient.
Claim 38 of the ‘947 application teaches that the personalized cancer antigens are selected based on NGS analysis of tumor DNA relative to the DNA from a blood sample from the subject with the tumor.
Sahin and Tureci teach that one of the critical challenges for personalized cancer vaccines is to accurately map the cancer mutanome so as to detect the most suitable mutations for optimal immune response (page 3/6, lines 1-4 under the heading “Mutation discovery, and selection of target antigens…”). Sahin and Tureci teach that personal mutations are detected by comparing exome sequencing data generated by NGS from tumor tissue and matched healthy tissue such as the patient’s blood cells, thereby preventing the incorrect classification of germline variants as neoepitopes (page 3/6, lines 4-9 under the heading “Mutation discovery, and selection of target antigens…”).
It would have been prima facie obvious at the time of prior to the effective filing date to generate a mutanome by carrying out the NGS of the patient’s tumor tissue relative to the exome of healthy blood cells of the patient. One of skill in the art would have been motivated to do so by the teachings of Sahin and Tureci regarding the need to accurately map the cancer mutanome, and the need to sequence the exome of the patients healthy blood cells in order to avoid misclassification of a germline variant as a neoepitope.
This is a provisional nonstatutory double patenting rejection.
Applicant argues that the ‘947 application is later filed, and that the M.P.E.P. dictates that the rejection should be withdrawn if the rejection is the only one remaining. This is not persuasive due to the remaining rejections of record.
The provisional rejection of claims 92-103, 109-112, 115, 116, 118, 120, 121, and 123-127 on the ground of nonstatutory double patenting as being unpatentable over claims 131-171 of copending Application No. 18/807,315(reference application) is withdrawn in light of applicant’s amendments in the instant claims.
. .
The provisional rejection of claims 92, 93, 96, 98-100, 102, 103, 114-116 are on the ground of nonstatutory double patenting as being unpatentable over claim 73-103 of copending Application No. 18/756,934 in view of Sahin and Tureci (Science, March 2018, Vol. 359, pp. 1355-1360) is withdrawn in light of abandonment of the ‘934 application.
All claims are rejected.
Conclusion
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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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643