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 .
DETAILED ACTION
Election/Restrictions
Claims 1-33 are pending in this application. Claims 1 and 2 are amended.
Applicant’s election without traverse of invention, Group I, claims 1-4, 8-15, and 17-33 in the reply filed on 06/22/2026 is acknowledged.
Claims 5-7, 16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/22/2026.
Applicant’s election without traverse of species in the reply filed on 06/22/2026 is acknowledged.
Claim 1: (i) Vesicular stomatitis virus glycoprotein (VSVG)(K47Q), SEQ ID NO: 98.
Claim 2: CD19.
Claims 4, 9: VSVG K47Q, SEQ ID NO: 98.
Claim 10: Therapeutic protein.
Claims 12, 21, 28: a zinc finger, CRISPR-Cas proteins.
Claims 13, 22 & 29: DNMT3A in Table 4, SEQ ID NO: 93.
Claims 15, 24, & 31: hAKT1, SEQ ID NO: 67.
Claims 17 and 25 (i).
Claims 19 and 26: Diagnostic protein.
Claims 1-4, 8-15, and 17-33 are under consideration.
Priority
This application has a provisional application, 63/425,894 that was filed on 11/16/2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 02/08/2024, 04/15/2024, 05/30/2024, 06/04/2024, 06/11/2024, 08/09/2024, 09/13/2024, 10/21/2024, 12/19/2024, 04/16/2025, 06/20/2025, 01/13/2026, 06/22/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 12, 15, 21, 28, 31, 32, 33 are objected to because of the following informalities:
Claims 12, 21, 28: Change “zinc finger” to zinc finger nuclease” for consistency with the art.
Claim 15: For consistency amongst claims, change “The VLP or of claim 9” to “The VLP or ptVLP of claim 9).
Claim 31: Change “The cells of claim 25” to “The cell of claim 25”.
Claim 32: Change “The cells of claim 25” to “The cell of claim 25”.
Claim 33: Change “The cells of claim 32” to the “The cell of claim 32”. Change “HEK293 T cells” to “HEK293T cells” for consistency with the art.
Appropriate correction is required.
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.
Claims 25-31 are 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 25 and its dependent claims 26-31 read on a cell within a human organism that has been targeted by, for example, a vector entity with or without additional cargo. To overcome the rejection in claim 25, change “cell” to “isolated cell”.
Claim Rejections - 35 USC § 112
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 1-4, 8-15, 17-33 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 1: Claim 1, as written, is unclear. For example, it is unclear if the claim reads on “A fusion protein comprising 1) a programmable tropism glycoprotein” (and that’s the end of the claim) or 2) envelope protein (ptENV) comprising…”. Alternatively, it is unclear if the claim reads on “a fusion protein comprising 1) glycoprotein or 2) ptENV, wherein either 1) or 2) is fused to a targeting domain…”. It is unclear what is meant by “a programmable tropism”.
Claim 4: It is unclear what “set forth herein means”. Also, it is unclear if “targeting domain” is optional.
Claims 8 and 9(c): Claim 8 and 9(c) recites “a cargo disposed in the core”. The meaning of “disposed in the core” is unclear.
Claim 13: It is unclear what “set forth herein” means.
Claims 15, 24, and 31: The term “preferably” in claims 15, 24, 31 is a relative term which renders the claim indefinite. The term “preferably” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 22: It is unclear what “set forth herein” means.
Claim 29: It is unclear what “set forth herein” means.
Claims 4, 9, 13, 15, 17, 22, 24, 25, 29, 31, reference Tables 1-6, which are presented in the instant Specification, but are not present in the instant claims. "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); see MPEP 2173.05(s).
Claim Rejections - 35 USC § 102/ § 103
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.
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.
Claims 1, 3, 4, 8, 9, 17, 18, 25, 32, 33 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Najjar et al. (Najjar)(WO2022013872A1)(See PTO-892 Notice of References Cited).
See claims 1, 3, 4, 8, 9, 17, 18, 25, 32, 33 as submitted 06/22/2026.
Regarding claims 1, 8, Najjar teaches reference claim 1: A pseudotyped virus or virus-like particle (as recited in instant claim 8, “a virus-like particle (VLP) comprising the fusion protein of claim 1”) comprising a fusion protein comprising a vesicular stomatitis virus envelope glycoprotein (VSVG) extracellular domain (ECD) or a fragment or an analog thereof capable of fusing with a cellular membrane linked to a polypeptide comprising an antigen binding domain (reads on instant claim 1, “targeting domain”) specific to cluster of differentiation 3 (CD3). Najjar also teaches reference claim 2: The pseudotyped virus or virus-like particle according to claim 1, wherein the polypeptide is a single variable fragment (scFv) of an antibody that specifically binds CD3 (reads on instant claim 1, “wherein the targeting domain comprises a…single chain variable fragment (scFv). Najjar further teaches “The present invention is based on the surprising finding that a fusion protein comprising an N-terminal anti-CD3 scFv and a C-terminal VSVG polypeptide separated by a peptide linker can produce virus particles that not only target and infect T-cells but also have reduced binding to the native cellular target receptor of VSVG, the LDL receptor”[067].
Regarding claim 3, Najjar teaches reference claim 6, “wherein said full- length VSVG comprises a signal peptide and comprises or consists of SEQ ID NO: 1 or wherein said full-length VSVG is devoid of a signal peptide and comprises or consists of SEQ ID NO: 60”. Review of the SEQ ID NOS provided within the reference indicate that the signal sequence is “MKCLLYLAFLFIGVNC” which is a 100% match for the instant application’s SEQ ID NO: 2, “MKCLLYLAFLFIGVNC”.
Regarding claim 4, Najjar teaches “Mutant viral envelope glycoprotein (K47Q), SEQ 33 with 100% identity to that the instant application SEQ ID NO: 98 (see Result #1, BKO04606, us-18-511-416-98.minpct95.rag, 07/31/2026, in supplemental contents tab).
Regarding claim 9, Najjar teaches with respect to the VLP, “According to any one of the above embodiments, the virus is a virus having a lipid bilayer envelope” [0130]. Najjar also teaches embodiments where the virus is either a DNA or an RNA virus. Najjar also further identifies embodiments where the virus is selected from enveloped viruses like lentiviruses, Epstein-Barr virus (EBV), Herpes Simplex Virus, etc. [0130]. Viral envelopes are built from phospholipid bilayers (reads on instant claim 9(a) “a membrane comprising a phospholipid bilayer”). Applicant elected VSVg K47Q, SEQ ID NO: 98 with a 100% match to reference application, SEQ 33 as noted above for the rejection of instant claim 4 (reads on claim 9(b), “the fusion protein…”).
Regarding claims 17, 18, 25, 32, 33, Najjar teaches “a method of producing these pseudotyped viruses” (Abstract). Najjar also teaches “A pseudotyped virus can be generated by a complementation cell line comprising polynucleotides sufficient for packaging of the pseudotyped virus. In some embodiments, a pseudotyped virus is generated by expressing an envelope protein in a cell (as recited in instant claim 25). In some embodiments, a pseudotyped virus is generated by expressing a gag-pol protein in a cell. In some embodiments, a pseudotyped virus is generated by expressing a reverse transcriptase in a cell. In some embodiments, the cell is a cell of a cell line…In some embodiments, the cell line is a packaging cell line. Packaging cell lines are cell lines that have high expression and are robust in culture. Cells such as 293 and 293T (as recited in instant claims 32 and 33) can be used among many others known in the art” [0114]. Najjar further teaches, Example 7. Preparation of VSVG-OKT3 and VSVG-CD8a-OKT3 pseudotyped LV (a different embodiment) which outlines the production of the respective pseudotyped lentivirus and then testing of the lentiviruses, which implies a “harvesting” step as recited in instant claim 18 [0212].
In view of the foregoing, all the claimed limitations are found in one reference and are
taught to be optional variations to a base product and process they exemplify. As such, the
claimed product and process recited in claims 1, 3, 4, 8, 9, 10, 17, 18, 25, 32, 33 is within the scope of Najjar’s invention, and thus Najjar’s invention renders claims 1, 3, 4, 8, 9, 10, 17, 18, 25, 32, 33 prima facie obvious. The rationale to support this conclusion of obviousness is that Najjar provides a teaching, suggestion, and motivation to substitute different variables disclosed within the reference. Furthermore, there is no evidence on the record that indicates that the claimed product and process exhibit any unexpected results compared to the prior art.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Najjar as applied to claims 1, 3, 4, 8, 9, 10, 17, 18, 25, 32, 33 above, and further in view of Frank et al. (Frank)(See PTO-892 Notice of References Cited).
See claim 2 as submitted 06/22/2026.
Najjar teaches claim 1 with a targeting domain that is a single variable fragment (scFv) but not one specific to CD19 (as recited in claim 2).
Frank, however, teaches details about targeting ligands, B lymphocyte-targeted lentiviral vectors and T lymphocyte-targeted lentiviral vectors (p. 23-26). Frank teaches “For the generation of truly cell type-specific LVs, the targeted receptor should ideally be exclusively expressed on the target cell population. There are two candidates that make an excellent pick for B lymphocyte targeting due to their expression in cells of the B cell lineage, but not in any other cell type (Table 1). The first is the cell surface marker CD20, a protein expressed on B cells in all stages of development with the exception of early pro- and pre-B cells, plasma blasts, and plasma cells…The second candidate marker for B cell targeting is CD19, which is present on all cells of the B lymphocyte lineage except terminally differentiated plasma cells…Both proteins are thought to play a role in B cell activation”(p. 26). Frank also teaches “To target B cells in all developmental stages, CD19-MV-LV was generated by displaying a CD19-specific scFv…CD19-MV-LV was shown to mediate efficient and exclusive transduction of CD19+ cells in mixed cultures even if only 1% of the total cell population was positive for CD19. Like CD20-MV-LV and CD20-TPMV-LV, CD19-MV-LV stably transduced both fully activated and resting primary human CD19+ B cells, albeit with slightly lower efficiency. Transduced quiescent B cells transiently upregulated the activation markers CD69 and CD71 and transitioned from G0 to G1b phase, indicating minimal activation. Although the exact mechanism still remains to be explored, crosslinking of the target receptor by LV particles displaying multiple scFv molecules resulting in signaling is the most likely scenario”(p. 25).
Frank further teaches “As main players of the humoral immune response, B lymphocytes have been in the focus of genetic modification strategies as well. Best known for their ability to produce antigen-specific immunoglobulins, they can also act as antigen-presenting cells (APCs) to induce specific immune activation or immune tolerance. Given these essential functions, the genetic modification of B cells is of great interest for both, basic research and therapeutic applications. For instance, B lymphocytes were modified to express costimulatory molecules or pro-inflammatory cytokines for the improvement of their antigen-presenting function. Lee and colleagues…could demonstrate enhanced antigen presentation by B cells that co-expressed the costimulatory ligands OX40L and 4-1BBL and the pro-inflammatory cytokine IL-12p40, which led to the induction of an antigen-specific T cell response in vitro. A similar approach was used to improve immune recognition of B cell malignancies. Introduction of CD80 and granulocyte-macrophage colony-stimulating factor (GM-CSF) into leukemic B cells ex vivo induced an anti-leukemic immune response…In autoimmune disease, engineering of antigen presentation by B cells can be used to induce immune tolerance, e.g., by delivering genes encoding antigen-immunoglobulin G (IgG) fusion proteins”(p. 20).
For T lymphocyte-targeted LVs, Frank teaches “An obvious candidate receptor for vector retargeting toward T lymphocytes is the T cell-exclusive marker CD3, which is part of the TCR-CD3 receptor complex expressed on all T cell subsets, but not on other cells. Indeed, fusion of an OKT3-derived scFv specific for the CD3ε chain to the MLV glycoprotein led to a preferential transduction of T lymphocytes in vitro”(p. 26).
One of ordinary skill in the art would have been motivated to combine the teachings of Najjar (a fusion protein comprising a glycoprotein fused to a target domain) where the targeting domain (a single variable fragment (scFv)) binds to human CD19 as taught by Frank for the benefit of specifically targeting, for example, B lymphocytes, which play a major role in the humoral response, and genetically modify them to enhance their responses (See MPEP 2143, Rationale G. Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention).
One of ordinary skill in the art would have had a reasonable expectation of success with combining the teachings of Najjar and Frank, e.g., with the targeting domain binding to CD19 as taught by Frank. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated in the context of gene therapeutics, viral vector design, and immunology, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of
ordinary skill in the art before the effective filing date of the claimed invention.
Claims 8 (cargo), 9(c), 10, 11, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Najjar as applied to claims 1, 3, 4, 8, 9, 17, 18, 25, 32, 33 above and further in view of Lyu et al. (Lyu)(as cited on IDS submitted 09/13/2024, #753) and in view of Choi et al. (Choi)(as cited on IDS submitted 02/08/2024, #76).
See claims 8, 9, 10, 11, and 12 as submitted 06/22/2026.
Najjar teaches claim 1 but does not teach a cargo disposed in the core of the VLP, wherein the cargo is optionally fused to a phospholipid bilayer recruitment domain.
Regarding claims 8, 9, 11, and 12, Lyu, however, teaches “various delivery methods are being developed for transient expression of designer nucleases including Zinc Finger Nuclease (ZNF), Transcription Activator-Like Effector Nuclease (TALEN) and Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated (CRISPR/Cas) (reads on instant claims 11 and 12). Recently, virus-like particles are being used for gene editing…. In this review, [they] talk through commonly used genome editing nucleases, discuss gene editing delivery tools and review the latest literature using virus-like particles to deliver gene editing effectors”(p. 1, Abstract)(reads on instant claim 8’s “a cargo disposed in the core of the VLP).
Lyu further teaches “Nowadays, scientists are using VLPs as delivery tools to combine the high infection efficiencies of viral vectors and the transient feature of mRNA, protein and RNP delivery. These delivery tools package mRNAs, proteins or RNPs into viral capsids for efficient and safe genome editing. The most widely used capsids are lentiviral capsids”(p. 2). Lyu also uses the “cargo” terminology when referring to gene editing effectors (p. 5).
Lyu, though, does not teach wherein the cargo is optionally fused to a phospholipid bilayer recruitment domain.
Regarding claim 8, 9 (c), and 10, Choi, however, teaches “The CRISPR/Cas9 system provides an easy way to edit specific site/s in the genome and thus offers tremendous opportunity for human gene therapy for a wide range of diseases”(p. 627, Abstract)(reads on instant claim 10, “cargo is a therapeutic protein”). Choi also teaches pre-packaged Cas9 protein (Cas9P LV) in lentiviral particles for transient exposure and showed its effectiveness for gene disruption in cells, including primary T cells expressing specific single guide RNAs (sgRNAs)(p. 627, Abstract). Choi also teaches “To incorporate Cas9 protein within lentiviral particles (Cas9P LV), FLAG-tagged Cas9 sequence was fused to the N terminus of Gag containing an intervening heterologous phospholipase C-δ1 pleckstrin homology domain (reads on instant claim 8 and 9 (c), “fused to a phospholipid bilayer recruitment domain”). This pleckstrin homology domain is thought to promote the recruitment of Gag and Gag Pol to the membrane. Finally, Choi teaches “one major concern for clinical use in humans is the propensity for off-target effects. It has been well documented that off-target effects are a common problem with CRISPR/cas9 system…One of the main determinants of off-target effects is the amount and duration of Cas9 expression, implying that a transient exposure to Cas9 would increase its specificity…Thus, to reduce off-target effects resulting from long-term expression of Cas9, we took advantage of a recently described system to deliver pre-packed proteins within lentiviral particles that has also been used to deliver ZFN protein for safer gene editing in cells”(p. 628).
One of ordinary skill in the art would have been motivated to combine the teachings of Najjar (fusion protein of claim 1) with teachings of Lyu, e.g., cargo that is a gene editing or epigenetic modulating reagent such as Zinc Finger Nuclease and CRISPR-Cas protein while also incorporating a phospholipid bilayer recruitment domain as taught by Choi for the benefit of reducing off-target effects resulting from long-term expression of Cas9, for example, to design a therapeutic that enables gene editing for genes implicated in disease (See MPEP 2143, Rationale A. Combining prior art elements according to known methods to yield predictable results and Rationale G, Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention).
One of ordinary skill in the art would have had a reasonable expectation of success with combining the teachings of Najjar (fusion protein) with those of Lyu and Choi that use a cargo zinc finger nuclease or CRISPR-Cas protein as well as including cargo, like CRISPR-Cas fused to a phospholipid bilayer recruitment domain as taught by Choi. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated in the context of gene therapeutics, viral vector design, and immunology, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of
ordinary skill in the art before the effective filing date of the claimed invention.
Claims 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Najjar in view of Lyu and Choi as applied to claims 8-12 above, and further in view of Jaenisch et al. (Jaenisch)(WO2018035495A1)(See PTO-892 Notice of References Cited).
See claims 13 and 14 as submitted 06/22/2026.
Najjar, Lyu and Choi teach claim 12 but do not teach DNMT3A (SEQ ID NO: 93) nor do they teach one or more guide RNAs and/o crRNAs that bind to and direct the CRISPR-Cas protein to a target nucleic acid sequence.
Regarding claims 13 and 14, Jaenisch, however, teaches “Mammalian DNA methylation is a epigenetic mechanism orchestrating gene expression networks in many biological processes. However, investigation of the functions of specific methylation events remains challenging. It is demonstrated that fusion of Tetl or Dnmt3a with a catalytically inactive Cas9 (dCas9) enables targeted DNA methylation editing” [0004]. Jaenisch also teaches “methods of modulating the methylation of one or more genomic sequences in a cell, the methods comprising introducing into the cell a catalytically inactive site specific nuclease fused to an effector domain having methylation or demethylation activity; and a guide sequence or a nucleic acid that encodes a guide sequence, thereby modulating the methylation of one or more genomic sequences in a cell” [0007].
Regarding claim 13, Jaenisch more specifically teaches DNA (cytosine-5)-methyltransferase 3A (DNMT3A) and the inactive dCas90Dnmt3a fusion gene encoded protein, SEQ 157 with 100% Query Match to instant SEQ ID NO: 93 (See Result #3, BFC61074, us-18-511-416-93.minpct95.rag, 07/31/2026, in supplemental contents tab).
One of ordinary skill in the art would have been motivated to use the cargo, e.g., the inactive dCas90Dnmt3a fusion gene encoded protein as taught by Jaenisch for the advantage of modifying one or more genomic sequences within a targeted cell. This type of construct could be used not only for epigenetic mechanism studies but also for diagnostic purposes or for therapeutic purposes in a patient (See MPEP 2143, Rationale A. Combining prior art elements according to known methods to yield predictable results).
One of ordinary skill in the art would have had a reasonable expectation of success with incorporating a cargo like inactive dCas90Dnmt3a fusion gene encoded protein as taught by Jaenisch. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated in the context of gene therapeutics, viral vector design, and immunology, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of
ordinary skill in the art before the effective filing date of the claimed invention.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Najjar in view of Lyu and Choi as applied to claims 8-12 above, and further in view of Joung et al. (Joung)(WO2020252455-A1)(as cited on IDS submitted 02/08/2024, #46).
See claim 15 as submitted 06/22/2026.
Najjar, Lyu, and Choi teach claim 9. Choi also teaches pleckstrin homology domain.
Joung, however, teaches reference claim 1, “ An engineered human-derived virus-like particle (heVLP), comprising: a membrane comprising a phospholipid bilayer with one or more HERV-derived ENV/glycoprotein(s) on the external side; a HERV-derived GAG protein in the heVLP core, and a cargo disposed in the core of the heVLP on the inside of the membrane, wherein the cargo is fused to a human-endogenous GAG or other plasma membrane recruitment domain, and the heVLP does not comprise a non-human gag and/or pol protein. Joung also teaches reference claim 3, “wherein the cargo is a gene editing reagent” …and/or CRISPR-based genome editing or modulating protein; a nucleic acid encoding a zinc finger (ZF)…and/or CRISPR-based genome editing or modulating protein”. Joung also teaches reference claim 6, “wherein the gene editing reagent comprises a CRISPR- based genome editing or modulating protein, and the heVLP further comprises one or more guide RNAs that bind to and direct the CRISPR-based genome editing or modulating protein to a target sequence”.
Joung also specifically teaches Human AKT1 pleckstrin homology domain, SEQ ID 25 with 100% Query Match with instant SEQ ID NO: 67 (see Result #1, BIT26824, us-18-511-416-67.minpct95.rag, 07/31/2026, in supplemental contents tab).
One of ordinary skill in the art would have been motivated to substitute the cargo of Najjar, Lyu and Choi, with that of Human AKT1 pleckstrin homology domain, SEQ ID 25 as taught by Joung for the benefit of reducing off-target effects resulting from long-term expression of Cas, for example when used in a construct as a therapeutic that enables gene editing for genes implicated in disease in a patient (See MPEP 2143, Simple substitution of one known element for another to obtain predictable results).
One of ordinary skill in the art would have had a reasonable expectation of success with incorporating Human AKT1 pleckstrin homology domain, SEQ ID 25 as taught by Joung. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated in the context of gene therapeutics, viral vector design, and immunology, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of
ordinary skill in the art before the effective filing date of the claimed invention.
Claims 17-21, 23-28, 30-33 are rejected under 35 U.S.C. 103 as being unpatentable over Najjar as applied to claims 1, 3, 4, 8, 9, 17, 18, 25, 32, 33 above, and further in view of Joung.
Claim 17-21, 23-28, 30-33 as submitted 06/22/2026.
Najjar teaches claim 1, aspects of claim 17 (not specifically the cargo), and 25 (not cargo).
Regarding claim 17, Joung, however, teaches reference claim 9, “A method of producing a heVLP comprising one or more cargo molecules, the method comprising: providing a cell expressing one or more HERV-derived envelope proteins, one or more HERV-derived GAG proteins, and the one or more cargo molecules, wherein the cell does not express a gag and/or pol protein, except for gag proteins that are encoded in the human genome or gag proteins that are encoded by a consensus sequence that is derived from gag proteins found in the human genome; and maintaining the cell under conditions such that the cells produce heVLPs”.
Regarding claim 18, Joung teaches reference claim 10, “The method of claim 9, further comprising harvesting and optionally purifying and/or concentrating the produced heVLPs”.
Regarding claim 19, Joung teaches reference claim 11, “wherein the cargo molecule is a therapeutic or diagnostic protein or nucleic acid encoding a therapeutic or diagnostic protein, or a small molecule therapeutic or diagnostic agent”.
Regarding claim 20, Joung teaches reference claim 12, “wherein the cargo molecule is a gene editing reagent”.
Regarding claim 21, Joung teaches reference claim 13, “wherein the gene editing reagent comprises a zinc finger (ZF)…and/or CRISPR-based genome editing or modulating protein; a nucleic acid encoding a zinc finger (ZF)…and/or CRISPR-based genome editing or modulating protein”.
Regarding claim 23, Joung teaches reference claim 15, “wherein the gene editing reagent comprises a CRISPR-based genome editing or modulating protein, and the heVLP further comprises one or more guide RNAs that bind to and direct the CRISPR-based genome editing or modulating protein to a target sequence”.
Regarding claim 24, Joung teaches Human AKT1 pleckstrin homology domain, SEQ ID 25 with 100% Query Match with instant SEQ ID NO: 67 (see Result #1, BIT26824, us-18-511-416-67.minpct95.rag, 07/31/2026, in supplemental contents tab).
Regarding claim 25, Joung, however, teaches reference claim 17, “A cell that expresses, in combination: one or more HERV-derived envelope proteins; one or more HERV-derived GAG proteins; and a cargo molecule, preferably fused to a human endogenous GAG or other plasma membrane recruitment domain (reads on instant claim 25, “phospholipid bilayer recruitment domain”), wherein the cell does not express non-human gag protein.
Regarding claim 26, Joung teaches reference claim 18, “wherein the cargo molecule is a, as elected, diagnostic protein.
Regarding claim 27, Joung teaches reference claim 19, “wherein the cargo molecule is a gene editing reagent.
Regarding claim 28, Joung teaches reference claim 20, “wherein the gene editing reagent comprises a zinc finger (ZF)…and/or CRISPR-based genome editing or modulating protein; a nucleic acid encoding a zinc finger (ZF)…and/or CRISPR-based genome editing or modulating protein”.
Regarding claim 30, Joung teaches reference claim 22, “the gene editing reagent comprises a CRISPR- based genome editing or modulating protein, and the heVLP further comprises one or more guide RNAs that bind to and direct the CRISPR-based genome editing or modulating protein to a target sequence”.
Regarding claim 31, Joung teaches reference claim 23, “wherein the cargo molecule comprises a fusion to a human-endogenous GAG or other plasma membrane recruitment domain, preferably as shown in Table 6”. Joung more specifically teaches Human AKT1 pleckstrin homology domain, SEQ ID 25 with 100% Query Match with instant SEQ ID NO: 67 (see Result #1, BIT26824, us-18-511-416-67.minpct95.rag, 07/31/2026, in supplemental contents tab).
Regarding claim 32, Joung teaches reference claim 24, “wherein the cells are primary or stable human cell lines”.
Regarding claim 33, Joung teaches reference claim 25, “which are Human Embryonic Kidney (HEK) 293 cells, HEK293 T cells”.
One of ordinary skill in the art would have been motivated to combine the teachings of Najjar (particularly claim 1) with that of Joung (cargo) to arrive at the current invention of a virus like particle that can deliver cargo molecules into cells to aid in the diagnosis of disease or processes. Additionally, one of ordinary skill in the art would have been motivated to combine the teachings of Najjar (particularly claim 1) with that of Joung (cargo) in for the benefit of introducing a gene editing or epigenetic modulating reagent into the cell to facilitate diagnostics (See MPEP 2143, Rationale A. Combining prior art elements according to known methods to yield predictable results).
One of ordinary skill in the art would have had a reasonable expectation of success with combining the teachings of Najjar and Joung. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated in the context of gene therapeutics, viral vector design, and immunology, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of
ordinary skill in the art before the effective filing date of the claimed invention.
Claim 22 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Najjar in view of Joung as applied to claims 17-21, 23, 25-28, 30-33 above, and further in view of Jaenisch.
See claim 22 and 29 as submitted 06/22/2026.
Najjar and Joung teach claim 1, 17, 21, and 28 but do not teach DNMT3A, SEQ ID NO: 93.
As noted above for claim 13, Jaenisch, however, teaches DNA (cytosine-5)-methyltransferase 3A (DNMT3A) and the inactive dCas90Dnmt3a fusion gene encoded protein, SEQ 157 with 100% Query Match to instant SEQ ID NO: 93 (See Result #3, BFC61074, us-18-511-416-93.minpct95.rag, 07/31/2026, in supplemental contents tab).
One of ordinary skill in the art would have been motivated to use the cargo, e.g., the inactive dCas90Dnmt3a fusion gene encoded protein as taught by Jaenisch for the benefit of modifying one or more genomic sequences within a targeted cell. This type of construct could be used not only for epigenetic mechanism studies but also for diagnostic purposes, too (See MPEP 2143, Rationale A. Combining prior art elements according to known methods to yield predictable results).
One of ordinary skill in the art would have had a reasonable expectation of success with incorporating a cargo like inactive dCas90Dnmt3a fusion gene encoded protein as taught by Jaenisch. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated in the context of gene therapeutics, viral vector design, and immunology, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of
ordinary skill in the art before the effective filing date of the claimed invention.
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.
Claims 1, 8, 9, 10, 11, 12, 14, 25, 26, 27, 28, 30, 32, 33 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, 9, 10, 11, 12, 14, 25, 27, 28, 30, 32, 33 of copending Application No. 18511459 (reference application) in view of Najjar (above). Although the claims at issue are not identical, they are not patentably distinct from each other.
See claims 1, 8, 9, 10, 11, 12, 14, 25, 26, 27, 28, 30, 32, 33 as submitted 06/22/2026.
Application No. 18511459 teaches:
Claim 1: 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
Claim 8: A virus-like particle (VLP) comprising the tENV of claim 1.
Claim 9: A minimal virus-like particle (mVLP), comprising: a membrane comprising a phospholipid bilayer and the tENV of claim 1; a cargo disposed in the core of the mVLP, wherein the cargo is
Claim 10: The mVLP of claim 9, wherein the cargo is a therapeutic or diagnostic protein or nucleic acid encoding a therapeutic or diagnostic protein, or a chemical.
Claim 11: The mVLP of claim 9, wherein the cargo is a gene editing or epigenetic modulating reagent.
Claim 12: The mVLP of claim 9, wherein the gene editing or epigenetic modulating reagent comprises a zinc finger (ZF), transcription activator-like effector (TALE),and/or CRISPR-Cas protein, variant, or fusion thereof; a nucleic acid encoding a zinc finger (ZF), transcription activator-like effector (TALE), and/or CRISPR-Cas protein, variant, or fusion thereof; a guide RNA and/or crRNA; or a ribonucleoprotein complex (RNP) comprising a CRISPR-Cas protein, variant, or fusion thereof and a guide RNA.
Claim 14: The mVLP of claim 12, wherein the cargo comprises a CRISPR-Cas protein or a fusion thereof, and the mVLP further comprises one or more guide RNAs that bind to and direct the CRISPR-Cas protein to a target nucleic acid sequence.
Claim 25: A cell expressing the tENV of claim 1, and a cargo.
Claim 27: The cell of claim 25, wherein the cargo is a gene editing or epigenetic modulating reagent.
Claim 28: The cell of claim 25, wherein the gene editing or epigenetic modulating reagent comprises a zinc finger (ZF), transcription activator-like effector (TALE), and/or CRISPR-Cas protein, variant, or fusion thereof; a nucleic acid encoding a zinc finger (ZF), transcription activator-like effector (TALE), and/or CRISPR-Cas protein, variant, or fusion thereof; a guide RNA and/or crRNA; or a ribonucleoprotein complex (RNP) comprising a CRISPR-Cas protein, variant, or fusion thereof and a guide RNA.
Claim 30: The cell of claim 28, wherein the gene editing or epigenetic modulating reagent comprises a CRISPR-Cas protein, and the mVLP further comprises one or more guide RNAs that bind to and direct the CRISPR-Cas protein to a target sequence.
Claim 32: A primary or stable human cell line comprising cells expressing the tENV of claim 1, and a cargo.
Claim 33: The primary or stable human cell line of claim 32, which are Human Embryonic Kidney (HEK) 293 cells or HEK293 T cell.
Application No. 18511459 does not teach targeting domain (as recited in claim 1).
Najjar, however, teaches the targeting domain that binds to antigens on target cells as described above.
One of ordinary skill in the art would have been motivated to combine the teachings of Application No. 18511459 and that of Najjar (targeting domain) for the benefit of developing a composition that could target a more specific cell for either therapeutic or diagnostic purposes (See MPEP 2143, Rationale A. Combining prior art elements according to known methods to yield predictable results.
One of ordinary skill in the art would have had a reasonable expectation of success for combining the teachings of Application No. 18511459 and that of Najjar (glycoprotein fused to a targeting domain). There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated in the context of gene therapeutics, viral vector design, and immunology, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of
ordinary skill in the art before the effective filing date of the claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims allowed.
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/C.C./Examiner, Art Unit 1672
/M FRANCO G SALVOZA/Primary Examiner, Art Unit 1672
Prosecution Insights