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 .
Election/Restrictions
Applicant’s election without traverse of Group 1, and species elections SEQ ID NO: 4 (central portion sequence), SEQ ID NO: 43 (tENV sequences), gene editing reagent (cargo types), SpCas9 (gene-editing or epigenetic reagents), and Pleckstrin homology domain of human AKT1 comprising E17K mutation (plasma membrane recruiting domains) in the reply filed on 5/20/2026 is acknowledged.
Claims 10 and 25-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions and species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5/20/2026.
Claims 1-16 and 25-33 are pending.
Claims 1-9 and 11-16 are under examination.
Priority
Applicant’s claim for the benefit of a prior-filed application provisional application 63/425,890 filed on 11/16/2022 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
The disclosure of the prior-filed application, Application No. 63/223,245, filed on July 19th, 2021 fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Application No. 63/223,245 fails to provide support for newly amended claim 2, which recites a central portion comprising a deletion of at least 1, 2, 3, 4, 5, 6, 7, 8 amino acids of the N terminus of SEQ ID NO: 4.
If applicant believes the earlier applications provide support for this disclosure, applicant should point out such support with particularity by page and line number in the reply to this Action.
Information Disclosure Statement
The information disclosure statements filed 4/16/2025, 6/20/2025, 10/14/2025, and 5/20/2026 fail to comply with the provisions of 37 CFR 1.98(a)(4) because they lack the appropriate size fee assertion. It has been placed in the application file, but the information referred to therein has not been considered as to the merits.
The information disclosure statements (IDS) submitted on 12/19/2024, 10/21/2024, 9/13/2024, 8/9/2024, 6/11/2024, 6/4/2024, 4/15/2024, and 2/8/2024 are considered by the examiner.
Drawings
The drawings are objected to because Figure 4 is too faint to discern. 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.
Specification
The specification filed 11/16/2023 is accepted by the examiner.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 recites “a signal sequence comprising the MKCLLYLAFLFIGVNCK (SEQ ID NO:1)”. Proper English is “a signal sequence comprising the sequence MKCLLYLAFLFIGVNCK (SEQ ID NO:1)”.
Appropriate correction is required.
Applicant is advised that should claim 1 be found allowable, claim 2 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim 2 comprises a deletion of “at least” one amino acid of SEQ ID NO: 4, representing the central portion. Claim 1 requires a sequence that is at least 95% identical to SEQ ID NO: 43. Because SEQ ID NO: 43 already comprises the central portion region, a deletion of at least one amino acid would still fall within 95% identity of SEQ ID NO: 43. Therefore, claim 2 shares the same scope as claim 1.
Claim Rejections - 35 USC § 112(a)- Written Description
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 1-9 and 11-16 are 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.
Claim 1 recites “A truncated glycoprotein/envelope protein (tENV) comprising a sequence that is at least 95% identical to one of SEQ ID NO:42-89, comprising: an N-terminal portion comprising a signal sequence, optionally comprising the MKCLLYLAFLFIGVNCK (SEQ ID NO: 1), fused to a central portion of a GS domain from a Vesicular stomatitis virus Glycoprotein (VSV-G) protein or homolog, ortholog, or paralog thereof, which is fused to a C-terminal portion comprising a transmembrane domain and an intracellular domain.”
SEQ ID NO: 43 was elected for examination.
As written, the base claim requires a sequence at least 95% identical to SEQ ID NO: 43 to comprise the following structures:
an N-terminal portion comprising a signal sequence represented by SEQ ID NO: 1
a central portion of a GS domain of a VSV-G protein or homolog, ortholog, or paralog thereof
a C-terminal portion comprising a transmembrane domain and an intracellular domain.
The central portion may comprise a deletion of at least 1, 2, 3, 4, 5, 6, 7, or 8 amino acids of the N terminus of SEQ ID NO: 4 (claim 2).
The central portion may comprise SEQ ID NO: 4 (claim 3).
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. 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. The disclosure of a single species is rarely, if ever, sufficient to describe a broad genus, particularly when the specification fails to describe the features of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue Pharma L.P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000).
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.). See also In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997).
SEQ ID NO: 43 represents a tENV sourced from a VSV glycoprotein truncated at position 448 (Table 1).
The working examples do not use a tENV comprising SEQ ID NO: 43, nor with modifications to the central portion as recited in claims 2 and 3.
The working examples of the instant specification teach mVLPs applied to K562 cells to modify VEGFs3.1 (e.g., pg. 48). The only tENV derived from a VSVG is truncated at position 421 it appears (e.g., SEQ ID NO: 41), based on Figs. 3 and 4. The specification does not provide any evidence that SEQ ID NO: 43 would possess the same activity as SEQ ID NO: 41.
Additionally, the working examples teach eVLPs pseudotyped with VSVG alone or a combination of VSVG and BaEVTRless comprising different PH domains fused to Cas9. Figure 5 demonstrates the difference in gene modification based on the PH domain used. However, the elected PH domain species (Pleckstrin homology domain of human AKT1 comprising E17K mutation), is not found in this figure. Figure 6 shows gene editing with an AKT1 (E17K)-Cas9, but only with VSVG + BaEVTRless, not VSVG alone. Only the presence of VSVG is required by the claim language. Further, in this working example, there is no information on what tENV is used or what type of Cas9 is utilize as cargo. As such, the specification does not provide any evidence that an eVLP comprising AKT1-SpCas9 cargo, SEQ ID NO: 43, and/or the elected PH domain (AKT1 with E17K mutation) would possess the same activity as the eVLPs taught in the working examples.
Gutierrez-Guerrero, Alejandra, et al. "Baboon envelope pseudotyped “Nanoblades” carrying Cas9/gRNA complexes allow efficient genome editing in human T, B, and CD34+ cells and knock-in of AAV6-encoded donor DNA in CD34+ cells." Frontiers in genome editing 3 (2021): 604371. is considered relevant prior art for comparing nanoblades (e.g., VLPs) co-pseudotyped with VSVG and BaEVRless to nanoblades pseudotyped only with VSVG or BaEVRless (Abstract). The group found that MLV-based nanoblades co pseudotyped with VSV-G and BaEV gps were more efficacious for gene editing in cell lines than single gp pseudotyped nanoblades Interestingly, when both envelopes were present on the MLV-based nanoblades, more than two fold higher Cas9 protein levels had incorporated than when either of the two envelopes (BaEV or VSVG) was present alone. This observation suggested that the combination of both envelope glycoproteins helped recruiting Cas9 protein and the associated gRNAs into
the nanoblades (e.g., pg. 6, col 2, last para; Fig. 2).
The specification provides minimal guidance on the modifications of the tENV that can occur and also result in a functioning tENV (e.g., pg. 10). The specification largely re-iterates the claim language, and fails to disclose what homologs, orthologs, and paralogs of VSV-G would share the same functional properties. Further, the entirety of elected species SEQ ID NO: 4 is not found in SEQ ID NO: 43 (the first 8 amino acids of SEQ ID NO: 4 are not found in SEQ ID NO: 43). The specification fails to provide guidance on how an artisan would possess a tENV comprising SEQ ID NO: 43 (e.g., shares 100% identity), which comprises a central portion represented by SEQ ID NO: 4. Thus, the ordinary artisan would not know what modification(s) can/must be made in order to fulfill the instant recitation (e.g., if the prior art teaches a sequence at least 95% identical to SEQ ID NO: 43, is this teaching sufficient to fulfill the limitations of claims 1-3? How would an artisan have a tENV sequence 100% identical to SEQ ID NO: 43, while also fulfilling the limitation of the central portion of SEQ ID NO: 43 comprising all (or part) of SEQ ID NO: 4?).
Parks et al. (US20210040158A1, published 2/11/2021) (discussed further in prior art rejections) is considered relevant prior art for teaching the different outcomes obtained when utilizing VSV-Gs truncated at differing lengths. Figure 21 shows that the presence of the VSV-G vectors in supernatant after infecting cells was dependent on the length of the GS central domain used (e.g., [0128]). In summary, Parks et al. teach that the sequence/length of the central domain can impact the function of the viral particle.
The instant specification does not provide support for a central portion comprising a deletion of at least 1, 2, 3, 4, 5, 6, 7, 8 amino acids of the N terminus of SEQ ID NO: 4, as recited in newly amended claim 2. Page 3 of the specification teaches deletions in the central portion comprising SEQ ID NO: 2, which is 42 amino acids in length. In comparison, SEQ ID NO: 4 is 23 amino acids in length. Instead, when referencing SEQ ID NO: 4, the instant specification only teaches the central portion comprising or consisting of this sequence (e.g., no modification to SEQ ID NO: 4) (pgs. 3 and 10).
Claim Rejections - 35 USC § 112(b)
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 12 and 15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 12, which depends upon claim 9, recites “the gene editing or epigenetic modulating reagent. There is insufficient antecedent basis for this limitation in the claim. The recitation is indefinite because there is no prior reference to a gene editing or epigenetic modulating reagent in claims 9 or 12. Therefore, the metes and bounds of the claim is not clearly and precisely defined. It would be remedial to amend claim 12 to depend upon claim 11. For purposes of compact prosecution, the claim will be considered to depend from claim 11.
With regard to claim 15, this claim is indefinite because it makes reference to Table 6 for phospholipid bilayer recruitment domains.
MPEP 2173.05(s) states: “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. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993)(citations omitted).”
In the instant case, the domains can be easily incorporated into the claim.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 5-7 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 5 recites “A nucleic acid sequence encoding the tENV of claim 1.” Claim 5 does not require the protein of claim 1.
Claim 6 recites “a vector comprising a nucleic acid sequence encoding the tENV of claim 1, operably linked to a promoter for expression of the tENV of claim 1.” Claim 6 does not require the tENV protein of claim 1. Instead, it is only required to be in the process of making the protein.
Claim 7 recites “a host cell comprising the nucleic acid sequence encoding the tENV of claim 1, and expressing the tENV of claim 1.” The host cell is “expressing” tENV, so the claim does not require the full protein of claim 1 to be present. Instead, it is only required to be in the process of making the protein.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-9 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Parks et al. (US20210040158A1, published 2/11/2021).
Parks et al. discloses recombinant vesicular stomatitis viruses for use as prophylactic and therapeutic vaccines for infectious diseases of AIDS (Abstract).
Regarding claims 1, 4, and 5, Parks et al. discloses a tENV comprising instant SEQ ID NO: 43. Fig. 19C of Parks et al. discloses SEQ ID NO: 13, representing an amino acid sequence of the G-Stem (e.g., central portion of GS domain of VSVG). One of the variants disclosed by Parks et al. is a short stem, which comprises SEQ ID NO: 43.
Below, the italicized portion of SEQ ID NO: 13 of Parks et al. corresponds to the signal sequence (shares 100% identity with instant SEQ ID NO: 1). The bolded portion of SEQ ID NO: 13 corresponds to the short (e.g., truncated) GS domain. The underlined portion of SEQ ID NO: 13 is instant SEQ ID NO: 43 (e.g., only S of Parks et al. short GS is not in SEQ ID NO: 43).
MKCLLYLAFLFIGVNCKASGYKFPLYMIGHGMLDSDLHLSSKAQVFEHPHIQDAASQLPDDESLFFGDTGLSKNPIELVEGWFSSWKSSIASFFFIIGLIIGLFLVLRVGIHLCIKLKHTKKRQIYTDIEMNRLGK
Further, SEQ ID NO: 13 of Parks et al. discloses SEQ ID NO: 4 (FFGDTGLSKNPIELVEGWFSSWK; FFGDTGL portion is not included in bold/underline portion above) (claim 3). Parks et al. also discloses the short GS not comprising the first 7 amino acids of SEQ ID NO: 4 (Fig. 19c) (claim 2).
Parks et al also notes that “the truncated form of G, called G-Stem (FIG. 18A), retains amino acid sequences that are essential for directing insertion of the molecule into the membrane (the signal peptide), anchoring the protein in the viral envelop or cellular lipid bilayer (the transmembrane domain; TM), and promoting incorporation into the budding viral particle (C-terminal domain)” (e.g., C-terminal domain reads on intracellular domain, and pg. 9 of the instant specification teaches the VSVG intracellular domain amino acids sequence being KLKHTKKRQIYTDIEMNRLGK, which is found in SEQ ID NO: 13).
Parks et al. discloses these tENVs in vectors (e.g., [0125]) (claim 6), virus-like particles (e.g., [0017]) (claim 8), and expressed in host cells (e.g., Fig. 21) (claim 7).
Claim Rejections - 35 USC § 103
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.
Claim(s) 1-9, 11-14, and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Parks et al. (US20210040158A1, published 2/11/2021) and further in view of Montagna, Claudia, et al. (Montagna, Claudia, et al. "VSV-G-enveloped vesicles for traceless delivery of CRISPR-Cas9." Molecular therapy Nucleic acids 12 (2018): 453-462.)
As shown above, the base claims are obvious over the base art.
Parks et al. does not teach the tENV being in a minimal VLP as described in claim 9.
An Artisan, interested in viral-like particles, would be aware of Montagna et al. for teaching VSVG-enveloped vesicles for delivering CRISPR-Cas9.
Montagna et al. teaches vesicles (referred to as VEsiCas) (reads on minimal virus-like particles) comprising a membrane decorated with fusogenic VSV-G glycoprotein, with SpCas9 complexed to sgRNA (e.g., cargo) (claims 11-14) encapsulated within the vesicle (e.g., Fig. 1B). While Montagna et al. doesn’t explicitly state the presence of a phospholipid bilayer, it is well known in the art that vesicles have lipid bilayers. Additionally, Montagna et al. used the polyethyleneimine (PEI) method to create the vesicles (e.g., pg. 459, col 2, first sentence). The fusogenic properties of VSV-G were used to deliver the cargo (e.g., cargo is fused to a phospholipid bilayer recruitment domain, as VSV-G is part of the phospholipid bilayer of the vesicle) (e.g., pg. 458, col 1, para 1). To minimize the viral elements, Montagna et al. obtained protein cargo delivery with vesicles made exclusively with the envelope glycoprotein of the vesicular stomatitis virus (VSV-G) (e.g., no exogenous gag, pro, or pol protein) (e.g., pg. 453, col 2, bottom half). The efficacy of the vesicles were tested in multiple cell lines (claim 16) (e.g., pg. 456, “VEsiCas Editing Efficiency in Cells and In Vivo”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the current invention to substitute the VSV-G in the mVLP taught by Montagna et al. with the tENV taught by Parks et al. with a reasonable expectation for success. An artisan would have a reasonable expectation of success because the simple substitution of one known element for another (e.g., glycoproteins) would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).” M.P.E.P. §2144.06.
Further, there is nothing to suggest that the truncated glycoprotein taught by Parks et al. would not function in the mVLP of Montagna et al. Both references teach VSV glycoproteins in viral particles. One would be motivated to replace the VSV glycoprotein taught by Montagna et al. because as taught by Parks et al., achieving significant expression of G-Stem fusion proteins in infected cells and on virus particles requires optimization of the Stem domain (e.g., [0129]). Additionally, Parks et al. found the vectors comprising short stem (ss) VSV-G were present in higher levels than the longer forms (long and medium) (e.g., [0128]).
Claim(s) 1-9 and 11-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Parks et al. and Montagna, Claudia, et al., as applied to claims 1-9, 11-14, and 16 above, and further in view of Yi et al. (Kyung H. Yi, et al. "Functional analysis of non-hotspot AKT1 mutants found in human breast cancers identifies novel driver mutations: implications for personalized medicine." Oncotarget 4.1 (2012): 29.).
As shown above, the base claims are obvious over the base art.
Parks et al. and Montagna et al. do not teach the phospholipid bilayer recruitment domain fused to the cargo of the mVLP being Pleckstrin homology (PH) domain of human AKT comprising an E17K mutation.
An Artisan, interested in AKT1 mutations, would be aware of Yi et al. for studying phosphatidylinositol 3-kinase (PI3-kinase)-Akt-mTOR pathway mutations.
Yi et al. studied AKT1 mutations by packaging AKT1 expression constructs into VSV-G envelope pseudotyped retroviruses and transiently transfecting 293T cells (pg. 32, “AKT1 expression constructs”). One of these constructs comprised a PH domain with the E17K mutant fused to GFP (e.g., pg. 30, “Results”, col 1; Fig. 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the current invention to substitute the phospholipid bilayer recruitment domain in the mVLP taught by Parks et al. and Montagna et al. with the PH domain comprising the E17K mutation taught by Yi et al. with a reasonable expectation for success. An artisan would have a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).” M.P.E.P. §2144.06.
Further, there is nothing to suggest that the PH domain taught by Yi et al. would not function in the mVLP of Parks et al. and Montagna et al. All references teach VSV glycoproteins in viruses/viral particles. One would be motivated to replace the domain taught by Parks et al. and Montagna et al. because as taught by Yi et al., the AKT1 E17K mutation in the PH domain constitutively activates Akt1 by altering the kinetics and specificity of phospholipid binding, increasing the binding to PIP2, the more abundant plasma membrane phospholipid in the absence of PI3 kinase activation (e.g., active in signal transduction and membrane localization) (e.g., pg. 30, col 2).
Double Patenting
The Examiner notes that the instant claims are similar to the claimed invention of U.S. Patent No. 12319938B2, but are not presently considered nonstatutory double patenting. As currently written, the instant application claims do not require the presence of a CRISPR-based genome editing protein and PH domain together in a particle, as required in patent claim 1. However, depending on future claim amendments, a nonstatutory double patenting rejection may be appropriate
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.
Claims 1-9 and 11-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-16 of copending Application No. 18/511,416 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because instant application is a species of the reference application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1: Reference claim 1 is drawn to a fusion protein that may encompass the tENV of instant claim 1. Reference claim 3 further limits the signal sequence to be identical to instant SEQ ID NO:1. Reference claim 4 further recites a ptENV comprising a glycoprotein or envelope protein from Table 1, which includes VSVG and VSVG truncations such as 448 (e.g., instant SEQ ID NO: 43).
Claim 5: Reference claim 5 is drawn to a nucleic acid sequence of the fusion protein.
Claim 6: Reference claim 6 is drawn to a vector comprising the nucleic acid.
Claim 7: Reference claim 7 is drawn to a host cell comprising the nucleic acid.
Claims 8 and 9: Reference claims 8 and 9 are drawn to a VLP comprising the fusion protein of claim 1 (which may comprise the tENV of the instant application).
Claim 11: Reference claim 11 further limits the cargo of the VLP to a gene editing or epigenetic modulating reagent.
Claim 12: Reference claim 12 further limits the gene editing or epigenetic modulating reagent (same list recited in instant claim 12).
Claim 13: Reference claim 13 further limits the cargo to species recited in Tables 2, 3, 4, and 5, which includes the Cas9 variants recited in instant claim 13.
Claim 14: Reference claim 14 further limits the cargo to a CRISPR-Cas protein further encompassing one or more guide RNAs.
Claim 15: Reference claim 15 further limits the phospholipid bilayer recruitment domain to species recited in Table 6, which includes the PH domain comprising AKT1 with an E17K mutation as recited in instant claim 15.
Claim 16: Reference claim 16 recites a method of delivering cargo to a cell by contacting the cell with the VLP of claim 9.
The invention is obvious over the reference, as the reference claims a product encompassing the product used in the claimed method. The Artisan would use the product and expect success, as it is claimed subject matter.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALLISON M JOHNSON whose telephone number is (703)756-1396. The examiner can normally be reached Monday-Friday 9am-5pm.
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, Tracy Vivlemore can be reached at (571) 272-2914. 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.
ALLISON M. JOHNSON
Examiner
Art Unit 1638
/ALLISON MARIE JOHNSON/Examiner, Art Unit 1638
/ROBERT M KELLY/Primary Examiner, Art Unit 1638
Prosecution Insights