DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
Applicant’s claim to priority for US Application 62/819,320 filed 03/15/2019 is acknowledged.
Application Status
This action is written in response to Applicant’s correspondence received 07/13/2026.
Amendments to claims filed 07/13/2026 are hereby acknowledged.
Claims 1, 24, 33-35 are amended. Claims 14, 18- 23, 25 and 27 are cancelled. Claims 29-30 and 33-45 are withdrawn. Claims 1-13, 15-17, 24, 26, 28-45 are currently pending. Claims 1-13, 15-17, 24, 26, 28 and 31-32 are under examination in this office action.
Any rejection or objection not reiterated herein has been overcome by amendment.
Applicant’s amendments and arguments have been thoroughly reviewed but are not persuasive to place all the claims in condition for allowance for the reasons that follow.
The following rejections are maintained from previous Office Action dated 04/22/2026 :
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. §102 and §103 (or as subject to pre-AIA 35 U.S.C. §102 and §103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. §103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. §103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or non-obviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. §102(b)(2)(C) for any potential 35 U.S.C. §102(a)(2) prior art against the later invention.
Claims 1-3, 8, 13, 15-17, 26 and 31-32 are rejected under 35 U.S.C. § 103 as being unpatentable over Malone (PG Pub NO: US 20220088224 A1, provisional application No. 62/733,015, filing date of 18 September 2018; previously cited), as evidenced by the HUGO Gene Nomenclature Committee (see HGNC pdf-1 and pdf-2 downloaded 12/17/2025 from internet at https://www.genenames.org/data/genegroup/#!/group/1409 , first published in November 2018) and at https://www.genenames.org/data/genegroup/#!/group/671, first published in November 2018, previously cited ), and in view of Yun (PG Pub No.: US 2005/0002965 A1; previously cited).
Regarding claims 1 and 26, Malone is drawn to a capsid comprising a recombinant engineered Arc polypeptide (i.e., a single, non-naturally occurring Gag-homology polypeptide) that can form a capsid (i.e., an export compartment) that may be loaded with heterologous molecules for delivery to a target of interest ([0003 ]).
In the provisional application No. 62/733,015, Malone teaches using Gag-like protein (see § [0002], [0005], [0044], [0052], [0057], [0075]). In § [0075], Malone teaches the use of non-endogenous capsid comprising protein encoded by a Retrotransposon Gag-like gene, which family comprises about 12 genes.
In Provisional application No. 62/733,015, Malone also teaches using non-endogenous capsid proteins from the Paraneoplastic Ma antigen family. Malone states in § [0074] that the Paraneoplastic Ma antigen family comprises about 14 members of neuro- and testis-specific proteins.
According to the HUGO Gene Nomenclature Committee pdf-1, the 12 genes that are in the Retrotransposon Gag like family are PEG10, RTL1/PEG11, RTL3, RTL4, RTL5, RTL6, LDOC1, RTL8A, RTL8B, RTL8C, RTL9 and RTL10.
According to the HUGO Gene Nomenclature Committee pdf-2, the Paraneoplastic Ma antigen family comprises 14 genes, which are PNMA1, PNMA2, PNMA3, MOAP1, PNMA5, PNMA6A, PNMA6B, PNMA6E, PNMA6F, ZCCHC12/PNMA7A, ZCCHC18/PNMA7B, PNMA8A, PNMA8B and PNMA8C.
Malone further teaches using Sushi-class proteins (in US Application No. 17/277,119), more specifically PEG10, RTL3, RTL6, RTL8A, RTL8B (see [0014], right column, lines 23-27). According to Applicant’s disclosure the Gag-homology protein of a Sushi-Class is like PEG10, RTL3, RTL10 or RTL1 (see instant Specification ¶ [0099]).
Malone teaches that the Arc polypeptide can self-assemble into a capsid ([0023 ]; see FIG. 3A for a depiction of a single Arc polypeptide self-assembling into a capsid). Malone teaches that the Arc capsid may comprise a therapeutic agent ([0004 ]). Malone further teaches that a second polypeptide can be linked to the Arc polypeptide through the use of a linker ([0012]).
Malone teaches that the capsid can comprise a protein selected from a wide range of protein families including Arc proteins, SCAN proteins, Sushi-Class proteins, and PNMA proteins (Gag-Homology proteins or endo-gag polypeptides) ([0102]-[0107]). Malone also teaches that the capsid can be an endo-Gag-based capsid ([0102]-[0107], [0256]-[0258]).
Malone also teaches that their delivery component may be an oncolytic virus ([0254]) wherein the viral envelope comprises a foreign or engineered protein that binds at the surface ([0255]).
Malone also teaches that in some embodiments, the delivery component (outer layer, liposome-like structure) can be a viral envelope ([0250]). Malone teaches that the viral envelope can be from an oncolytic virus, such as Herpesviridae, Poxviridae, Rhadoviridae (e.g. VSV) or Paramyxoviridae ([0254]). Malone teaches that in additional instances the viral envelope is derived from Retroviridae ([0253]).
Malone does not specifically teach a system wherein the non-naturally occurring polypeptide comprises an epitope tag for expression on the outer surface of the export compartment and wherein the export compartment comprises an epitope tag on the outer surface of the export compartment.
However, one of ordinary skill in the art would have considered the teachings of Yun as both references are analogous prior art pertaining to the study and use of therapeutic proteins.
Yun is drawn to an invention concerning the use of a recombinant adenovirus with a protein containing a VSV-G epitope derived from vesicular stomatitis virus (see Abstract). Yun teaches that a VSV-G epitope was attached to the C-terminus of an adenovirus fiber protein through the use of a glycine linker ([0017]; see FIG. 1). Yun teaches that a protein containing a VSV-G epitope has improved transduction efficiency ([0011]). Yun teaches that the protein containing a VSV-G epitope is linked to any position of the adenovirus proteins, including the adenovirus fiber, capsid, and penton base (i.e., the VSV-G epitope can be expressed on a capsid surface) ([0070]).
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to attach a VSV-G epitope tag via a glycine linker, as described by Yun, to a endo-gag polypeptide such that the polypeptide comprises a VSV-G epitope tag for expression on the outer surface of the capsid and wherein the export compartment comprises an epitope tag on the outer surface of the export compartment.
Malone also teach that oncolytic virus’s component can also be used. These oncolytic viruses contain fiber proteins that can be modified and added to the composition and design of the recombinant capsid.
A person of ordinary skill in the art would have been motivated to do so in order to improve the transduction efficiency of the self-assembled capsid. A person of ordinary skill in the art would have had a reasonable expectation of success
in attaching a VSV-G epitope tag via a glycine linker, as described by Yun, to the endo-gag polypeptide described by Malone because both references teach that their respective polypeptides can be linked to a second peptide through the use of a linker.
Thus, the claim is rejected as obvious.
Regarding claim 2, Malone teaches that the Arc polypeptide can comprise a capsid (i.e. an export compartment) assembly/forming domain ([0054]). Malone also teaches that the composition can comprise a nucleic acid molecule, a protein, or a binding fragment thereof (i.e., a carrier tag) ([0127]). Malone further teaches that a cargo (i.e., a target molecule) comprised of RNA ([0128]) can be utilized and can comprise a non-coding RNA (i.e., a cargo tag) ([0129]).
Regarding claim 3, Malone teaches that that a cargo comprised of RNA can be utilized ([0128]).
Regarding claim 8, Malone teaches that the cargo (i.e., a target molecule) can be a protein ([0127]).
Regarding claim 13, the specification teaches that the term "export compartment" refers to any particle delivery system that may be used for delivery including lipid-based systems ([0114 ]). Malone teaches that the delivery component can comprise a liposome, micelle, or micro vesicle ([023 7]). Malone further teaches that the delivery component further comprises a viral envelope protein for specifically targeting the capsid to a target cell ([0250]).
Regarding claim 15, Malone teaches that the Arc polypeptide can comprise a capsid (i.e. an export compartment) assembly/forming domain ([0054 ]). Malone also teaches that the Arc polypeptide can comprise an RNA (i.e., nucleic acid) binding domain ([0041]).
Regarding claims 16-17, Malone teaches that the Arc polypeptide can have its RNA (i.e. nucleic acid) binding domain modified (i.e., the RNA binding domain is non-native) when compared to the native nucleic acid binding site ([0041]).
Regarding claim 31, Malone teaches the use of a vector comprising DNA encoding the Arc polypeptide ([0006]).
Regarding claim 32, Malone teaches that the cargo can be delivered through the use of a multitude of drugs (i.e., a molecule that must inherently contain a pharmaceutical carrier) ([0158]).
Claims 4 and 6 are rejected under 35 U.S.C. § 103 as being unpatentable over Malone (PG Pub NO: US 20220088224 A1, provisional application No. 62/733,015, filing date of 18 September 2018; previously cited), as evidenced by the HUGO Gene Nomenclature Committee (see HGNC pdf-1 and pdf-2; 2018), in view of Yun (PG Pub No.: US 2005/0002965 A1; previously cited) as applied to claims 1-3 above, and further in view of Keryer-Bibens (Keryer-Bibens, C. et al. "Tethering of proteins to RNAs by bacteriophage proteins." Biology of the Cell 100.2 (2008): 125-138; previously cited).
Regarding claims 4 and 6, Malone in view of Yun makes obvious claims 1-3, 8, 13, 15-17, 26 and 31-32 as described above.
Malone in view of Yun lacks the structure wherein the carrier tag is LambdaN and the cargo tag is BoxB (Claim 4) and wherein the carrier tag is MS2 domain and the cargo tag is MS2 RNA (Claim 6).
However, one of ordinary skill in the art would have considered the teachings of Keryer-Bibens because both references are analogous prior art pertaining to the use of coding and non-coding RNA.
Keryer-Bibens is drawn to a study concerning the tethering of proteins to RNA (Abstract). Keryer-Bibens teaches that the LamdaN protein-B box system is well known in the art and teaches tethering a protein to a single box B element (pg. 127). Keryer-Bibens also teaches that the system is protected from RNase attack due to the asymmetrical nature of the binding between LamdaN and the box B element (pg. 131). Keryer-Bibens further teaches that the box B element binds to the LamdaN protein with a high Kct value (pg. 131). Keryer-Bibens teaches that through the use of the LambdaN-B box system genes downstream of the N protein can be transcribed (pg. 131). Keryer-Bibens teaches that the MS2 coat protein in a well-known system in the art commonly used for tethering a protein to an RNA (pg. 127). Keryer-Bibens teaches that tethering via the LambdaN-B box system or the MS2 system produced similar results (pg. 127). Keryer-Bibens further teaches that MS2 proteins are bifunctional and can act as both translational repressors of the replicase mRNA and as structural prate ins (pg.129).
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the carrier and cargo tags of Malone for the Lambda N-B Box tethering system or the MS2-MS2 RNA tethering system described by Keryer-Bibens. A person of ordinary skill in the art would have been motivated to do so in order to utilize two well-known systems in the art that allow for downstream expression of genes or the use of proteins that are bifunctional repressors of replicase mRNA and serve as structural proteins. A person of ordinary skill in the art would have had a reasonable expectation of success because Malone teaches the use of both carrier and cargo nucleic acid tags, so simply utilizing the nucleic acid molecules described in Keryer-Bibens as the carrier and cargo tags described in Malone would have resulted in the predictable outcome of success of utilizing the Lambda N-B Box tethering system or the MS2-MS2 RNA tethering system as the carrier and cargo tags. Thus, the claim is rejected as obvious.
Claim 5 is rejected under 35 U.S.C. § 103 as being unpatentable over Malone (PG Pub NO: US 20220088224 A1, provisional application No. 62/733,015, filing date of 18 September 2018; previously cited), as evidenced by the HUGO Gene Nomenclature Committee (see HGNC pdf-1 and pdf-2; 2018), and in view of Yun (PG Pub No.: US 2005/0002965 Al) as applied to claims 1-3 above, and further in view of Rozhdestvensky (Rozhdestvensky, T. et al. "Binding of L 7 Ae protein to the K-turn of archaeal snoRNAs: a shared RNA binding motif for CID and H/ACA box snoRNAs in Archaea." Nucleic acids research 31.3 (2003): 869-877; previously cited).
Regarding claim 5, Malone in view of Yun makes obvious claims 1-3, 8, 13, 15-17, 26 and 31-32 as described above.
Malone in view of Yun does not specifically teach a system wherein the carrier tag is L 7 Ae peptide and the cargo tag is CID box ( Claim 5). However, one of ordinary skill in the art would have considered the teachings of Rozhdestvensky as both references are analogous prior art pertaining to the use of specific nucleic acid molecules.
Rozhdestvensky is drawn to a study concerning the binding of the L7 Ae protein to CID Boxes in Archaea (Abstract). Rozhdestvensky teaches that the L 7 Ae-C/D Box system is well known in the art and that the RNA motif required for L7 Ae binding is a structure, designated as a K-Turn, which is present in all C/D box RNAs (pg. 869). Rozhdestvensky also teaches that the L7 Ae-C/D Box system is able to be implemented in a non-native system (such as Archaea) (pg. 869).
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the carrier and cargo tags taught by Malone with the L 7 Ae peptide and the CID box as taught by Rozhdestvensky. A person of ordinary skill in the art would have been motivated to do so in order to utilize a well-known protein-RNA tethering system. A person or ordinary skill in the art would have had a reasonable expectation of success because Rozhdestvensky teaches that the L7 Ae-CID Box system can be utilized outside of its native origins, so simply substituting the carrier and cargo tags in Malone for a system well known in the art would yield the predictable outcome of utilizing the L7 Ae peptide and the CID box as the carrier and cargo tags. Thus, the claim is rejected as obvious.
Claim 7 is rejected under 35 U.S.C. § 103 as being unpatentable over Malone (PG Pub NO: US 20220088224 A1, provisional application No. 62/733,015, filing date of 18 September 2018; previously cited), as evidenced by the HUGO Gene Nomenclature Committee (see HGNC pdf-1 and pdf-2 ; 2018), and in view of Yun (PG Pub No.: US 2005/0002965 A1; previously cited) as applied to claims 1-3 above, and further in view of Karn (Karn, J. "Tackling tat." Journal of molecular biology 293.2 ( 1999): 23 5-254; previously cited).
Regarding claim 7, Malone in view of Yun makes obvious claims 1-3, 8, 13, 15-17, 26 and 31-32 as described above.
Malone in view of Yun does not specifically teach a system wherein the carrier tag is a TAT peptide and the cargo tag is TAR RNA ( Claim 7). However, one of ordinary skill in the art would have considered the teachings of Karn as both references are analogous prior art pertaining to the study of non-coding RNA.
Karn is a study drawn to examining how the TAT peptide interacts with TAR RNA. Karn teaches that TAT is recruited into transcription machinery via a specific interaction with the TAR RNA regulatory element (pg. 235). Karn further teaches that the binding affinity between TAT and TAR RNA are mainly directed through an uracil-rich bulge on the TAR RN A and that other mutations affecting the structure of the TAR RNA did not abolish binding (pg. 237). Karn teaches that there is a strict correlation between the ability of TAR RNA to bind to the TAT peptide with the ability of sequences to support transactivation (pg. 238).
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the carrier and cargo tags taught by Malone with the TAT peptide and the TAR RNA as taught by Kam. A person of ordinary skill in the art would have been motivated to do so in order to utilize a well-known, highly specific protein-RNA tethering system that supports transactivation.
A person of ordinary skill in the art would have had a reasonable expectation of success because Malone teaches the use of both carrier and cargo nucleic acid tags, so simply utilizing the nucleic acid molecules described in Kam as the carrier and cargo tags described in Malone would have resulted in the predictable outcome of success of utilizing the TAT peptide and the TAR RNA as the carrier and cargo tags. Thus, the claim is rejected as obvious.
Claim 9 is rejected under 35 U.S.C. § 103 as being unpatentable over Malone (PG Pub NO: US 20220088224 A1, provisional application No. 62/733,015, filing date of 18 September 2018; previously cited), as evidenced by the HUGO Gene Nomenclature Committee (see HGNC pdf-1 and pdf-2; 2018), and in view of Yun (PG Pub No.: US 2005/0002965 A1; previously cited) as applied to claims 1, 2 and 8 above, and further in view of Virant (Virant, D. et al. "A peptide tag-specific nano body enables high-quality labeling for dSTORM imaging." Nature communications 9.1 (2 March 2018): 930; previously cited).
Regarding claim 9, Malone in view of Yun makes obvious claims 1-3, 8, 13, 15-17, 26 and 31-32 as described above. Malone further teaches that the invention is compatible for use with a cargo comprising a nano body ([0181 ]).
Malone in view of Yun does not specifically teach a system wherein the carrier tag is a BC2 nano body and the cargo tag is a BC2 peptide (Claim 9). However, one of ordinary skill in the art would have considered the teachings of Virant as both references are analogous prior art pertaining to the use of peptide tags.
Virant is drawn to a study concerning the use of both a BC2 nano body and a BC2 peptide for tagging of endogenous proteins (Abstract). Virant teaches that the use of a BC2-tag/bivBC2-Nb (i.e., a BC2 peptide-BC2 nanobody composition) labeling strategy results in higher quality visualization of target cells (pg. 2; Fig. 1, Fig. 1 description).
Therefore, it would have been obvious to a person of ordinary skill in the art before the filing date of the claimed invention to substitute the carrier and cargo tags taught by Malone with the BC2 nano body and BC2 peptide as taught by Virant. A person of ordinary skill in the art would have been motivated to do so in order to easily delivery a high-fidelity visualization reagents to a target cell of interest. A person of ordinary skill in the art would have had a reasonable expectation of success because Malone in teaches that the invention is compatible with both nano bodies and nucleic acids; therefore, simply substituting the BC2 nano body and BC2 peptide described by Virant for the carrier and cargo tags described by Malone would have resulted in the predictable outcome of utilizing the BC2 nanobody and BC2 peptide as the carrier and cargo tags. Thus, the claim is rejected as obvious.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Malone (PG Pub NO: US 20220088224 A1, provisional application No. 62/733,015, filing date of 18 September 2018; previously cited), as evidenced by the HUGO Gene Nomenclature Committee (see HGNC pdf-1 and pdf-2; 2018), and in view of Yun (PG Pub No.: US 2005/0002965 A1; previously cited) as applied to claims 1, 2 and 8 above, and further in view of Tanenbaum (Tanenbaum, M.E. et al. "A protein-tagging system for signal amplification in gene expression and fluorescence imaging." Cell 159.3 (2014): 635-646; previously cited).
Regarding claim 10, Malone in view of Yun makes obvious claims 1-3, 8, 13, 15-17, 26 and 31-32 as described above.
Malone in view of Yun does not specifically teach a system wherein carrier tag is a Sun tag antibody and the cargo tag is a Sun tag antibody (Claim 10). However, one of ordinary skill in the art would have considered the teachings of Tanenbaum as both references are analogous prior art pertaining to the use of non-coding RNA.
Tanenbaum is drawn to a study concerning a protein-tagging system for signal
amplification. Tanenbaum teaches that the Sun Tag system provides a versatile platform for multimerizing proteins on a target protein scaffold in order to control biological outputs (pg.635). Tanenbaum further teaches that Sun Tag can recruit multiple copies of an antibodies (i.e., SunTag antibodies) (Abstract; pg. 636-637). Tanenbaum teaches that the Sun Tag system is similar to the MS2 system (pg. 635) with the added benefit of controlling the copy number of protein-protein interactions in order to amplify the biological signals derived from the proteins (pg. 635). Tanenbaum further teaches that Sun Tag antibodies can be utilized in order to visualize
SunTag.
Therefore, it would have been obvious to a person of ordinary skill in the art before the filing date of the claimed invention to substitute the carrier and cargo tags taught by Malone in view of Yun with the Sun tag antibodies as taught by Tanenbaum. A person of ordinary skill in the art would have been motivated to do so in order to utilize a well-known system of controlling biological outputs. A person of ordinary skill in the art would have had a reasonable expectation of success because Malone teaches the use of both carrier and cargo nucleic acid tags, so simply utilizing the nucleic acid molecules that can recruit antibodies, as described in Tanenbaum, as the carrier and cargo tags described in Malone would have resulted in the predictable outcome of utilizing Sun Tag antibodies as the carrier and cargo tags. Thus, the claim is rejected as obvious.
Claim 11 is rejected under 35 U.S.C. § 103 as being unpatentable over Malone (PG Pub NO: US 20220088224 A1, provisional application No. 62/733,015, filing date of 18 September 2018; previously cited), as evidenced by the HUGO Gene Nomenclature Committee (see HGNC pdf-1 and pdf-2; 2018; previously cited), and in view of Yun (PG Pub No.: US 2005/0002965 A1; previously cited) as applied to claims 1, 2 and 8 above, and further in view of Kerscher (Kerscher, O. "SUMO junction-what's your function? New insights through SUMO-interacting motifs." EMBO reports 8.6 (2007): 550-555; previously cited).
Regarding claim 11, Malone in view of Yun makes obvious claims 1-3, 8, 13, 15-17, 26 and 31-32 as described above.
Malone in view of Yun does not specifically teach a system wherein the carrier tag is a SUMO domain and the cargo tag is a SIM peptide (Claim 11). However, one of ordinary skill in the art would have considered the teachings of Kerscher as both references are analogous prior art pertaining to the use and study of proteins.
Kerscher is drawn to a study concerning SUMO-interacting motifs. Kerscher teaches that SIM peptides interact with and bind to SUMO domains (pg. 551). Kerscher further teaches that SIM peptides interacting with SUMO domains could be used for DNA replication processes in order to enhance error-free replication and disrupt Rad51 nucleofilaments during replication (pg.552).
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the carrier and cargo tags taught by Malone with the SUMO domain and SIM peptides as taught by Kerscher. A person of ordinary skill in the art would have been motivated to do so in order to utilize a well-known binding motif in the art that is known to enhance error-free replication. A person of ordinary skill in the art would have had a reasonable expectation of success because Malone teaches the use of both carrier and cargo nucleic acid tags, so simply utilizing the nucleic acid molecules described in Kerscher as the carrier and cargo tags described in Malone would have resulted in the predictable outcome of utilizing the SUMO domain and SIM peptide as the carrier and cargo tags. Thus, the claim is rejected as obvious.
Claim 12 is rejected under 35 U.S.C. §103 as being unpatentable over Malone (PG Pub NO: US 20220088224 A1, provisional application No. 62/733,015, filing date of 18 September 2018; previously cited), as evidenced by the HUGO Gene Nomenclature Committee (see HGNC pdf-1 and pdf-2; 2018; previously cited), and in view of Yun (PG Pub No.: US 2005/0002965 A1; previously cited) as applied to claims 1, 2 and 8 above, and further in view of Eaton (Eaton, H. E. et al. "SIMPLE/LITAF expression induces the translocation of the ubiquitin ligase itch towards the Lysosomal compartments." PloS one 6.2 (2011): e16873; previously cited).
Regarding claim 12, Malone in view of Yun makes obvious claims 1-3, 8, 13, 15-17, 26 and 31-32 as described above.
Malone in view of Yun does not specifically teach a system wherein the carrier tag comprises one or more WW domains and the cargo tag is a PPXY domain (Claim 12). However, one of ordinary skill in the art would have considered the teachings of Eaton as both references are analogous prior art pertaining to the use of proteins.
Eaton is drawn to a study concerning the investigation of LIT AF expression through the interaction of two PPXY motifs with WW -domain containing proteins. Eaton teaches that the interaction between a protein that contain 4 WW domains, Nedd 4, and a protein that contains a PPXY motif, LITAF, are carried out through the ability of PPXY motifs to bind to WW domains (pg. 2 ). Eaton also teaches that Itch, a WW-domain containing protein, and LIT AF strongly interact through the same mechanism (pg. 1).
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the carrier and cargo tags taught by Malone with the 4 WW domain and the PPXY domain as taught by Eaton. A person of ordinary skill in the art would have been motivated to do so in order to utilize a well-known, very strong binding relationship between two known domains. A person of ordinary skill in the art would have had a reasonable expectation of success because Malone teaches the use of both carrier and cargo nucleic acid tags, so simply utilizing the nucleic acid molecules described in Eaton as the carrier and cargo tags described in Malone would have resulted in the predictable outcome of utilizing the 4WW domain and the PPXY domain as the carrier and cargo tags. Thus, the claim is rejected as obvious.
Claim 28 is rejected under 35 U.S.C. §103 as being unpatentable over Malone (PG Pub NO: US 20220088224 A1, provisional application No. 62/733,015, filing date of 18 September 2018; previously cited), as evidenced by the HUGO Gene Nomenclature Committee (see HGNC pdf-1 and pdf-2; 2018; previously cited), and in view of Yun (PG Pub No.: US 2005/0002965 A1; previously cited) as applied to claim 1 above, and further in view of Hung (Hung, M. E. et al. "A platform for actively loading cargo RNA to elucidate limiting steps in EV-mediated delivery." Journal of extracellular vesicles 5.1 (2016): 31027; previously cited ).
Regarding claim 28, Malone in view of Yun makes obvious claims 1-3, 8, 13, 15-17, 26 and 31-32 as described above.
Malone in view of Yun does not specifically teach a system wherein the export
compartment is a gesicle ( Claim 28). However, one of ordinary skill in the art would have considered the teachings of Hung as both references are analogous prior art pertaining to the delivery of RNA cargo to a desired target.
Hung is drawn to a study concerning loading cargo RNA in EV -mediated delivery. Hung teaches that gesicles can enrich cargo RNA loading by 40-fold (pg. 1). Hung further teaches that gesicles can be implemented in systems expressing VSVG in order to increase cargo RNA loading (pg. 1).
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the export compartment described by Malone for the gesicle described by Hung. A person of ordinary skill in the art would have been motivated to do so in order to increase cargo RNA loading. A person of ordinary skill in the art would have had a reasonable expectation of success in substituting the export compartment of Malone for the gesicle of Hung because Hung teaches that the gesicles can be implemented into the MS2 bacteriophage coat protein system (i.e., an engineered non-naturally occurring polypeptide that self-assembles into an export compartment analogous to the Arc polypeptide of Malone); therefore, one of ordinary skill in the art would have had a reasonable expectation of success in substituting the export compartment of Malone
for the gesicle of Hung. Thus, the claim is rejected as obvious.
Response to Arguments
Applicant's arguments filed 07/13/2026 have been fully considered but they are not persuasive.
Applicant states on Remarks, page 8, that “Claim 1 has been amended to recite “wherein the PEG10 is PEG10_i6 or PEG10_i2”, incorporating the allowable subject matter the Examiner acknowledged with respect to claim 24”.
Indeed, Examiner finds claim 24 to be allowable. Claim 24 is limited to an engineered non-naturally occurring polypeptide that self-assembles into an export compartment comprising these specific proteins PEG10, PEG10_i6 or PEG10_i2.
However, claim 1 is a Markush claim, allowing for alternatives to PEG10 proteins.
In response, Applicant is reminded of claim 1 language: “wherein the engineered non-naturally occurring polypeptide comprises a Gag-homology protein or a functional domain thereof, wherein the Gag-homology protein is a Sushi-Class protein selected from PEG10, RTL3, RTL10, and RTL1, or a paraneoplastic Ma antigen (PNMA) protein selected from…”.
The claim language encompasses the use of any of the proteins belonging to these classes of proteins. The claim language does not limit to a specific protein, for which motivation for selection of this specific protein would need to be established. One of ordinary skills in the art simply motivated in designing a virus-like particle, a nanoparticle for therapeutics delivery would be motivated in picking a protein with self-assembling properties, and so did Malone.
Double Patenting
A terminal Disclaimer was filed and approved on 09/15/2025.
Allowable Subject Matter
Claim 24 is allowed.
The following is a statement of reasons for the indication of allowable subject matter: Claim 24 is limited to allowable subject matter: engineered non-naturally occurring self-assembling PEG10_i6 or PEG10_i2 polypeptides as an export compartment. These proteins as included in a synthetic delivery vehicle are absent from prior art as of the effective filing date
Conclusion
Claim 24 is allowed.
Claims 1-13,15-17, 26, 28 and 31-32 are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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/A.D./Examiner, Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636
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