DETAILED ACTION
Election/Restrictions
Applicant’s election of Group I, and selected species, in the reply filed on June 21, 2026 is acknowledged. Because applicant did not distinctly and specifically point any supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 44 and 58 are withdrawn, being directed to non-elected subject matter.
Drawings
The drawings are objected to because Figures 7B, 7C, 21B, 21C, 22A and 26C have amino acid sequences that should be referenced with sequence identifiers.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
In lieu of filing corrected drawing sheets, Applicant may amend the specification’s description of the figures to include the sequence identifiers.
Claims Summary
Claim 1 is directed to an engineered arenavirus particle, wherein the genome of the arenavirus particle comprises:
An S segment that encodes
An arenavirus GP signal peptide
A buffer peptide that comprises or consists of a fragment of the arenavirus GP1, and wherein the fragment is shorter than the GP1 and comprises about, at most about, or at least about 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70 or more than 70 amino acids of the arenavirus GP1 (elected species from claims 1 and 6), and
A first heterologous non-arenaviral polypeptide
Wherein the signal peptide can be cleaved from the buffer peptide or a portion thereof by a signal peptide peptidase (claim 15, elected species)
Wherein the GP signal peptide, buffer peptide and first heterologous polypeptide are in that order in a fusion protein (claim 23, elected species)
An S segment that encodes
NP under the control of an arenavirus genomic 3’ UTR, and
A second, different (elected species of claim 1) heterologous non-arenaviral polypeptide under the control of an arenavirus genomic 5’ UTR; and
An L segment that encodes
The L protein under the control of an arenavirus genomic 3’ UTR, and
The Z protein the control of an arenavirus genomic 5’ UTR
The arenavirus particle is derived from Clade A (claim 21), specifically Pichinde virus (PICV) (claim 22). The inter-segmental recombination of the two S segments unites two ORFs on only one instead of two separate S segments, resulting in a bi-segmented arenavirus that is not viable or that in cell culture reaches peak titers that are lower than or equivalent to the tri-segmented arenavirus from which the bi-segmented arenavirus was recombined (claim 26).
The GP signal peptide fused to the buffer peptide comprises or consists of an amino acid sequence that is the sequence of amino acids 1-66 of SEQ ID NO: 3 (elected species, claim 28). SEQ ID NO: 3 is the amino acid sequence of the PICV GP precursor. The coding sequence of the first heterologous non-arenaviral polypeptide starts at about amino acid 60 or more than about 60 amino acids downstream of the methionine start codon of the GP signal peptide (claim 32). The first and second heterologous non-arenaviral polypeptides are each derived from a tumor neoantigen, tumor neo-epitope or tumor associated antigens, specifically a fusion protein of HPV16 E6 and E7 (claim 33, elected species).
Claim 38 is directed to a set of cDNAs from which the genomic segments of the engineered arenavirus particle can be transcribed. Claim 39 is directed to a set of DNA expression vectors comprising the cDNAs. Claim 40 is directed to a host cell comprising the set of cDNAs. Claim 41 is directed to a method of manufacturing an engineered arenavirus particle comprising maintaining the host cell of claim 40 under conditions suitable for virus formation and harvesting the engineered arenavirus particle. Claim 42 is directed to a pharmaceutical composition comprising the engineered arenavirus particle and a pharmaceutically acceptable carrier.
Claim 54 is directed to a method of immunizing a subject suspected of having, diagnosed with, or at risk of developing a disease or disorder (cancer (claim 73, elected species)), comprising:
Administering a first engineered arenavirus particle of claim 1 to the subject; and
Administering a second engineered arenavirus particle of claim 1, wherein the first and second are derived from a first and second, different arenavirus species (elected species)
The first species is LCMV and the second species is PICV, or vice versa (claim 61).
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.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claim 40 is rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101). Claim 40 is directed to a host cell which can be located in human being, thus reading on a human being. This rejection may be overcome by amending the claim to recite “isolated host cell” or equivalent language.
Claim Rejections - 35 USC § 112
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 1, 6, 15, 21-23, 26, 32, 33, 38-42, 54, 61 and 73 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. 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.
The claims are directed to an engineered arenavirus particle comprising a large genus of buffer peptides that comprise or consist of a fragment of the arenavirus GP1, and wherein the fragment is shorter than the GP1 and comprises about, at most about, or at least about 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70 or more than 70 amino acids of the arenavirus GP1.
According to paragraph [0041] of the published application US 2024/0229073, though not a definition of “buffer peptide”, Applicant proposes that “a buffer peptide can increase the cleavage efficiency by a peptidase at the cleavage site following the GP signal peptide.” Sections 5.4 and 5.6 of the specification provide copious amounts of possible structures in generic terms, i.e., no particular structures are provided in those sections. The examples show the following constructs, all of which yield replication-competent vector particles (see paragraphs [0525] and [0528] in the published application US 2024/0229073):
PICV-Split(66)-(TOM/E7E6), PICV-Split(66)-(TOM/Trp2), TCRV-Split(66)-(TOM/E7E6) and TAMV-Split(66)-(GFP/GFP), each containing the 7 N-terminal amino acids of PCV-GP
PICV-Split(81)-(TOM/E7E6), PICV-Split(81)-(TOM/Trp2) and TCRV-Split(816)-(TOM/E7E6) and TAMV-Split(81)-(GFP/GFP), each containing the 22 N-terminal amino acids of PCV-GP
PICV-Split(113)-(TOM/E7E6) and PICV-Split(113)-(TOM/Trp2) containing the 54 N-terminal amino acids of PCV-GP
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
In this case, Applicant has provided a partial structure in form of variable fragment sizes of arenavirus GP1 that are shorter than GP1. Fragments can be as little as 1 amino acid and fragments can be more than 60 amino acids. Applicant has provided base sequences from which the fragments can be taken, but do not indicate which part of the sequence is to be used as a buffer peptide. The base sequences are: SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:142 (this is a signal peptide), SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:54, SEQ ID NO:61, SEQ ID NO:68, SEQ ID NO:75, SEQ ID NO:86, SEQ ID NO:93, SEQ ID NO:100, SEQ ID NO:115, SEQ ID NO:122, SEQ ID NO:129, SEQ ID NO:136, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, SEQ ID NO:164, or SEQ ID NO:165 (see paragraph [0132] in the published application US 2024/0229073). These sequences are whole GP1 sequences, with no indication of which parts are to be used for the buffer peptides.
No function is assigned to the fragments other than “buffer peptide”. Based on the examples provided in the specification, Applicant has exemplified that the 7-, 22- and 54- N-terminal amino acids of GP1 in the PICV tri-segmented construct result in replication-competent vector particles. Constructs without the buffer peptide, generally, produced particles that were not replication competent (see paragraph [0526] in the published application US 2024/0229073), however, one of the constructs without a buffer peptide (PICV-Split(59)-(TOM/Trp2)) did produce infectious titer (see paragraph [0528] in the published application US 2024/0229073).
Given the broad and variable structure of the buffer peptide in the claims and the unclear function of the buffer peptide, there is no structure-function nexus from which one would be put in possession of other buffer peptides. The fact that one of the constructs without a buffer peptide produced replication competent viruses (see paragraph [0526] in the published application US 2024/0229073) speaks to the undefined structure-function nexus.
The limited examples (7-, 22- and 54- N-terminal aa of GP1) are not representative of the large genus claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived.
Conclusion
No claim is allowed.
Claim 28 is objected to for being dependent on a rejected claim.
The embodiment of a GP signal peptide fused to a buffer peptide, represented by amino acids 1-66 of SEQ ID NO: 3 (elected species in claim 28) is free of the prior art of record.
The prior art made of record and not relied upon is considered pertinent to Applicant's disclosure. Bonilla et al. (WO 2017/198726 A1, of record in the IDS filed 7/3/2024, “Bonilla”) discloses tri-segmented PICV vectors carrying heterologous polypeptides as vaccines and therapeutics (see abstract). Bonilla’s constructs, as represented in Figures 1B-1D, including an S segment encoding GP and a heterologous polypeptide, another S segment encoding NP and a heterologous polypeptide, and an L segment encoding L and Z, all having 3’ and 5’ UTRs and intergenic regions. However, Bonilla does not teach or fairly suggest that the GP portion of the construct have a truncation such that a fragment of GP1 is used in the construct, rather than a full-length GP1.
Zaza et al. (Virol J., June 7 2018, 15(1):99, 7 pages, “Zaza”) discloses a live-attenuated tri-segmented Machupa virus (of the Arenaviridae family). In Zaza’s construct, there are two S segments, each having a C-terminally truncated GP complex (GPC) (see Figure 1b) wherein 33 amino acids are deleted to render the resulting particle non-infectious (see page 2, left column, first full paragraph). Zaza’s truncation does not impact the GP1 portion of the GPC. Zaza does not teach or fairly suggest truncation of GP1 in the construct.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Stacy B. Chen whose telephone number is 571-272-0896. The examiner can normally be reached on M-F (7:00-4:30). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone, can be reached on 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/STACY B CHEN/Primary Examiner, Art Unit 1672
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