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 .
Response to Amendment
The Amendment filed 11/11/2025 in which claims 1, 2, 4, 7, 9, 10, 12-18 were amended, new claim 21 was added, and claims 19, 20 were canceled, has been entered.
Claims 1-18, 21 are under examination on the merits.
Priority
Applicant’s claim for domestic benefit of prior-filed provisional application No. 63/208,889 filed on 06/09/2021 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
It is noted that Applicant’s Remarks submitted on 11/11/2025 in reference to the Priority have been fully considered and found persuasive. Thus, domestic benefit of prior-filed provisional application No. 63/208,889 filed on 06/09/2021 is herein acknowledged.
Drawings
(Previous objection, withdrawn) Applicant’s amendments to the Drawings submitted on 11/11/2025 have overcome the objection previously set forth in the Non-Final Office Action mailed 08/11/2025.
Specification
(Previous objection, withdrawn) Applicant’s amendments to the Specification submitted on 11/11/2025 have overcome the objection previously set forth in the Non-Final Office Action mailed 08/11/2025.
Nucleotide and/or Amino Acid Sequence Disclosures
(Previous objection, withdrawn) Applicant’s amendments to the Specification concerning nucleotide and/or amino acid sequence disclosures submitted on 11/11/2025 have overcome the objection previously set forth in the Non-Final Office Action mailed 08/11/2025.
Claim Objections
(Previous objections, withdrawn as to claims 12-15). Applicant’s amendments to claims 12-15 have overcome previous objections to claims 12-15.
(New objections, necessitated by amendment as to claim 14). Claim 14 is objected to because of the following informalities:
On claim 14, the recitation of “the plurality of disparate APs has a sequence identity…” should read “the plurality of disparate APs have a sequence identity…”.
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.
(Previous rejection, maintained as to claims 1-18, expanded as to claim 21) Claims 1-18, 21 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.
See claims 1-18, 21 as submitted on 11/11/2025.
Regarding the previous rejection of claim 1 for reciting “a plurality of fusion proteins” in line 5, the Examiner acknowledges the amendment to the claim submitted on 11/11/2025. Amended claim 1 is no longer indefinite based on the indicated recitation.
Regarding the previous rejection of claim 1 for reciting “a plurality of fusion proteins are capable of self-assembling into an enveloped nanoparticle (ENP) secreted from a cell in which the fusion proteins are expressed, thereby generating a population of ENPs.” It is noted that there were no amendments to the indicated recitation. As such the indicated recitation remains unclear. As previously indicated, it is not clear whether the claim encompasses ENPs assembled each by a single fusion protein or a plurality of fusion proteins or both. While a cell might be able to constitutively express a fusion protein, that sole fact does not indicate whether each of the expressed fusion proteins self-assembles into a single ENP, or whether a plurality of fusion proteins is required to form a single ENP. The meets and bounds of the instant claims are not clear. Therefore, the rejection is maintained for reasons of record. The dependent claims do not provide additional clarity and therefore are also indefinite.
Regarding the previous rejection of claims 3, 9, and 10 for reciting “comprises or is derived from”. The Examiner acknowledges the amendment to the claims 9 and 10 submitted on 11/11/2025. Amended claims 9 and 10 are no longer indefinite based on the indicated recitation. With respect to claim 3, it is noted that no amendments were submitted to claim 3. Claim 3 still recites “comprises or is derived from”. Accordingly, the rejection of claim 3 is herein maintained. As previously indicated, it is not clear what the term “derived from” encompasses. For example, it is not clear if the term encompasses sequences comprising fragments of known ERD proteins, or sequences which share a degree of homology with known ERD proteins, or other. It should be noted that although the claims are interpreted in light of the Specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The meets and bounds of instant claim 3 are not clear. Therefore, the rejection of claim 3 as submitted on 11/11/2025 is maintained for reasons of record.
Regarding the previous individual rejections of claims 2, 14, 16, 17 under 35 U.S.C. 112 (pre-AIA ), second paragraph, the Examiner acknowledges the amendment to the claims submitted on 11/11/2025. The previous individual rejections of claims 2, 14, 16, 17 are herein withdrawn. However, these claims remain rejected as they are dependent on rejected claim 1.
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.
(Previous rejection, withdrawn as to claim 7, maintained and modified as necessitated by amendment as to claims 4 and 14, expanded as to claim 21) Claims 4, 14 and 21 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.
See claims 4, 14 and 21 as submitted on 11/11/2025.
Applicant’s amendment to claim 7 has overcome the previous rejection to claim 7.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See, e.g., Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010); University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) at 1406; Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ("[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).").
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The issue is whether the skilled artisan would understand inventor to have invented, and been in possession of, the invention as claimed.
The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568,43 USPQ2d l398, 1406 (Fed. Cir. 1997). The Court stated that a written description of an invention requires a precise definition, one that defines the structural features of the chemical genus that distinguishes it from other chemical structures. A definition by function does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is. Further, the Court held that to adequately describe a claimed genus, an applicant must describe a representative number of species of the claimed genus, and that one of skill in the art should be able to “visualize or recognize the identity of the members of the genus.”
Amended claim 4 requires an amino acid sequence having at least 70% sequence identity to an amino acid sequence selected from the group consisting of instant SEQ ID NOs: 1-3 and 12-20 and having the ability to recruit proteins via the ESCRT pathway. Amended claim 14 requires a plurality of disparate antigenic polypeptides (APs) with sequences having at least 70% sequence identity with one another and having the ability of surface display and the ability to retain antigenic properties. New claim 21 requires an (ESCRT)-recruiting domain (ERD) comprising an amino acid sequence having at least 70% sequence identity to an amino acid sequence of SEQ ID NOs: 4-11 and 23 and having ability to recruit ESCRT proteins to the cytoplasmic tail of the fusion protein.
However, the Specification has failed to sufficiently describe the structural features that must be retained by members of the claimed genera as to establish a structure-function relationship with respect to their respective functions of recruitment of proteins via the ESCRT pathway, as required by claim 4; the ability of surface display and the ability to retain antigenic properties as required by claim 14, and the ability to recruit ESCRT proteins to the cytoplasmic tail of the fusion protein as required by claim 21.
As to the genus of claim 4, for example SEQ ID NO: 1, e.g., is 52 amino acids long. The instant claims encompass any sequence having at least 70% sequence identity to SEQ ID NO: 1. An amino acid sequence sharing only 70% identity relative to SEQ ID NO: 1 could have anywhere from 1 to 15 substitutions, deletions, or additions in any combination along any length of SEQ ID NO: 1, which corresponds to a massive genus (2015 = 3.28 x 1019) comprising trillions upon trillions of sequences, with respect to SEQ ID NO: 1 alone. Furthermore, since claim 4 recites “at least 70% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-3 and 12-20”, the actual number of sequences encompassed by the genus is actually much greater.
As to the genus of claim 21, a similarly massive genus is encompassed by this claim. For example, SEQ ID NO: 4, e.g., is 54 amino acids long, the instant claim encompasses any sequence having at least 70% sequence identity to SEQ ID NO: 4. An amino acid sequence sharing only 70% identity relative to SEQ ID NO: 4 could have anywhere from 1 to 15 substitutions, deletions, or additions in any combination along any length of SEQ ID NO: 1, which corresponds to a massive genus (2015 = 3.28 x 1019) comprising trillions upon trillions of sequences, with respect to SEQ ID NO: 4 alone. Furthermore, since claim 21 recites “at least 70% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 4-11 and 23”, the actual number of sequences encompassed by the genus is actually much greater.
However, while for example, claim 4 is drawn to a genus that comprises innumerable sequences, the Specification has only adequately described and reduced to practice nine sequences to various degrees of success (¶ [0226], Table 2, FIG. 16). This is not representative of the extremely large genus of sequences claimed, especially since some of the sequences tested (S-Syntenin-12-60 and S-Hrs), failed to exhibit recruitment of proteins via the ESCRT pathway resulting in failure of ENP assembly (¶ [0226]).
At best, the Specification contemplates the use of BLAST to identify functional homologs based on sequence homology. However, this is not sufficient to describe members of the claimed genus because such methods access online databases that are continually being updated as sequencing technology improves. As a result, they are not a static source of information. Thus, one of skill in the art would readily appreciate that relying on a non-patent source that is continuously subject to change as a means to identify members of the claimed genus does not sufficiently meet the written description requirement.
Moreover, Friedberg (“Automated protein function prediction--the genomic challenge”. Brief Bioinform. 2006;7(3):225-242.) teaches that homology-based transfer is not reliable for functional annotation even with high alignment percentages (page 227, second column). Friedberg also teaches that identification of functionally significant sub-regions is critical to functional annotation, and that often addition, deletion, or re-shuffling of domains can lead to errors in annotation (page 227, second column; page 228, first paragraph). Furthermore, Friedberg teaches that sequence-based tools are just not sensitive enough to identify functional protein similarity as databases get larger, and diversity of sequences gets larger (page 228, first full paragraph).
Thorton (“Structural genomics takes off.” Trends Biochem Sci. 2001;26(2):88-89.) teaches that the same protein structure is often seen in apparently different homologous families with different functions. Thorton further describes examples of little correlation between specific binding function and overall protein structure (page 992, right column, at lines 2-10). Thus, when taken with the teachings of Friedberg and Thorton, one of skill in the art would readily appreciate that sequence homology alone cannot serve as the basis to describe members of the genus that have the recited function.
In the absence of a representative number of examples, the Specification must at least describe the structural features that are required for the claimed functions, in this case recruitment of proteins via the ESCRT pathway as required by claim 4, the ability of surface display and the ability to retain antigenic properties as required by claim 14, and the ability to recruit ESCRT proteins to the cytoplasmic tail of the fusion protein as required by claim 21. However, as discussed above, the Specification fails to describe any substantive structural limitations as to establish a structure-function relationship with respect to the claimed functions.
Accordingly, the claims as currently written are not adequately described and one of skill in the art would readily appreciate that Applicant was not in possession of the claimed genus at the time of filing.
Claim Rejections - 35 USC § 102
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 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.
(Previous rejection, maintained and modified as to claims 1-4, 8-10 and 16) Claims 1-4, 8-10 and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Votteler J et al. (prior art of record).
See claims 1-4, 8-10 and 16 as submitted on 11/11/2025.
Regarding claim 1, it is noted that the amendment was made to overcome the previous rejections under 35 U.S.C. 112(b), second paragraph set forth in the Non-Final Office Action mailed on 08/11/2025. No new limitations were introduced in the amendment filed on 11/11/2025. Accordingly, the rejection under 35 U.S.C. 103 set forth in the previous Non-Final Office Action mailed on 08/11/2025 still applies to amended claim 1. As previously explained, Votteler et al. disclose a polynucleotide encoding a fusion protein, wherein the fusion protein comprises the following elements:
a membrane binding element, (Abstract, page 1, Figs. 1A-C)
a self-assembly element, (Abstract, page 1, Figs. 1A-C)
a recruitment of the Endosomal Sorting Complexes Required for Transport (ESCRT) machinery element (an ESCRT-recruiting domain ERD, as recited in claim 1) and (Abstract, page 1, Figs. 1A-C)
an antigenic polypeptide (for example, a fragment of an HIV-1 Gag protein) (Abstract, page 1, Figs. 1A-C, Extended data Fig. 8).
Accordingly, the fusion protein of Votteler et al. is capable of self-assembling into an enveloped nanoparticle (ENP), wherein the fusion protein is secreted from a cell in which the fusion protein is expressed (Abstract, page 1, Figs. 1A-C).
Regarding amended claim 2, the new recitation of “wherein the ERD recruits one or more ESCRT proteins to the cytoplasmic tail of the fusion protein, thereby inducing the self-assembly and budding of ENPs” does not impart any additional structural features to the composition comprising a polynucleotide encoding a fusion protein as recited in claim 1, therefore this recitation is considered to flow from the features already present in the composition comprising a polynucleotide encoding a fusion protein as recited in claim 1. Therefore, any polynucleotide encoding a fusion protein in the prior art having the all of the structural limitations recited in claim 1 would be capable of displaying ERD recruitment of one or more ESCRT proteins to the cytoplasmic tail of the fusion protein, thereby inducing the self-assembly and budding of ENPs.
Further it is noted that the recitation indicated above is inherent to the polynucleotide of Votteler et al. because as indicated above such polynucleotide comprises a membrane binding element, a self-assembly element, and an ESCRT element which has the ability to recruit ESCRT machinery to the cytoplasmic tail of the fusion protein to catalyze the final membrane fission step required for release from the cell (page 2).
Regarding claim 3, it is noted that no amendments were introduced to claim 3 in the amendment filed on 11/11/2025. As previously explained, Votteler et al. disclose a recruitment of the Endosomal Sorting Complexes Required for Transport (ESCRT) element (an ESCRT-recruiting domain ERD comprising an HIV-1 p6 (page 2).
Regarding amended claim 4, it is noted that the amended claim recites SEQ ID NOs: 1-3 and 12-20. As previously explained, Votteler et al. disclose a sequence termed EPN-01 comprising an HIV-1 p6 amino acid sequence (Supplementary Table 2) which shares 100% identity to instant SEQ ID NO: 1. See alignment below (Qy is instant SEQ ID NO: 1, and Db is Votteler et al.’s EPN-01).
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Regarding claims 8-10, it is noted that the amendments to claims 9 and 10 were made to overcome the previous rejections under 35 U.S.C. 112(b), second paragraph set forth in the Non-Final Office Action mailed on 08/11/2025. No new limitations were introduced in the amendment filed on 11/11/2025 to claims 9 and 10. Accordingly, the rejection under 35 U.S.C. 103 set forth in the previous Non-Final Office Action mailed on 08/11/2025 still applies to amended to claims 8-10. As previously explained, Votteler et al. disclose an antigenic polypeptide, wherein the antigenic peptide is displayed on the surface of the ENP. The antigenic protein in Votteler et al.’s disclosure is for example a fragment of an HIV-1 Gag protein (a pathogen) causing acquired immunodeficiency syndrome (AIDS) (Abstract, page 1, Figs. 1A-C, Extended data Fig. 8).
Regarding claim 16, it is noted that the amendment was made to overcome the previous rejections under 35 U.S.C. 112(b), second paragraph set forth in the Non-Final Office Action mailed on 08/11/2025. No new limitations were introduced in the amendment filed on 11/11/2025. Accordingly, the rejection under 35 U.S.C. 103 set forth in the previous Non-Final Office Action mailed on 08/11/2025 still applies to amended claim 16. As previously explained, Votteler et al. disclose the polynucleotide of claim 1 comprising a vector, wherein the vector is for example a cytomegalovirus (CMV) vector (Supplementary Table 3).
Accordingly, claim 1-4, 8-10 and 16 were anticipated by the disclosure of Votteler et al. before the effective filing date, especially in the absence of evidence to the contrary.
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.
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.
(Previous rejection, maintained and modified as to claims 5-7) Claims 5-7 are rejected under 35 U.S.C. 103 as being unpatentable over Votteler J et al., as applied to claims 1-4, 8-10 and 16 above, in view of Miettinen et al. (prior art of record).
See claims 5-7 as submitted on 11/11/20025.
Regarding claim 5, it is noted that no amendments were introduced to claim 5 in the amendment filed on 11/11/2025. As previously explained, Votteler et al. teach the nucleic acid composition of claim 1, as explained above. Votteler et al. do not teach a fusion protein comprising an endocytosis-preventing motif (EPM) capable of preventing endocytosis of the fusion protein.
However, Miettinen et al. teach an endocytosis-preventing motif (EPM) comprising a region of the Fc receptor, which when expressed in cells it associates with the cell cytoskeleton and functions to prevent endocytosis and localization to coated pits. Miettinen et al. further teach such association blocks internalization of proteins comprising such EPM (Abstract, pages 3, 12, 13).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have incorporated the endocytosis-preventing motif (EPM) comprising an isoform of the Fc receptor as taught by Miettinen et al. into the nucleic acid composition of Votteler et al. for the benefit of preventing fusion proteins from localizing to coated pits and undergoing endocytosis, thereby blocking internalization. See MPEP 2144.07. 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)
One of ordinary skill in the art would have had reasonable expectation of success in incorporating the EPM of Miettinen et al. to the nucleic acid of Votteler et al. given that the methods of cloning and formulating fusion proteins with multiple motifs are well known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Regarding claim 6, it is noted that no amendments were introduced to claim 6 in the amendment filed on 11/11/2025. As previously explained, as indicated above, the EPM of Miettinen et al. associates with the cytoskeleton of the cell thereby preventing localization to coated pits and endocytosis.
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Regarding claim 7, the amended claim recites “wherein the EPM comprises the amino acid sequence of SEQ ID NO: 21”. As previously explained, Miettinen et al. teach a region of the Fc receptor comprising the EPM which shares 100% identity with instant SEQ ID NO: 21 (Fig. 1). See alignment below (Qy is instant SEQ ID NO: 21, and Db is Miettinen et al.’s Fc receptor B2/B1-R).
Accordingly, claims 5-7 were prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
(Previous rejection, maintained and modified as necessitated by amendments as to claims 12-15) Claims 12-15 are rejected under 35 U.S.C. 103 as being unpatentable over Votteler J et al., as applied to claims 1-4, 8-10 and 16 above, in view of King et al. (prior art of record).
See claims 12-15 as submitted on 11/11/2025.
Regarding claim 12, it is noted that the amendment was made to overcome the previous objection set forth in the Non-Final Office Action mailed on 08/11/2025. No new limitations were introduced in the amendment filed on 11/11/2025. Accordingly, the rejection under 35 U.S.C. 103 set forth in the previous Non-Final Office Action mailed on 08/11/2025 still applies to amended claim 12. As previously explained, Votteler et al. teach the amino acid composition of claim 1. Votteler et al. further teach that the enveloped nanoparticles (ENP) comprise additional proteins which may be expressed on the surface of the ENPs, such as a fragment of the HIV-1 Gag protein (Myristate) or a fragment of a VP40 protein from Ebola virus (Abstract, pages 3, 12, 13, Extended data Fig. 8).
Votteler et al. do not teach 2 or more polynucleotides each encoding a different fusion protein comprising different antigens or cargo proteins and displaying a plurality of disparate antigen or cargo proteins.
However, King et al. teach a nanostructure-based vaccine composition, wherein polynucleotides self-assemble into nanostructures or nanoparticles that display multimeric antigens capable of harnessing the advantages of subunit vaccines which rely only on antigens while increasing the potency and breadth of the vaccine-induced immune response through multivalent display of antigens (Abstract, column 2). The nanostructures taught by King et al. comprise antigen proteins, wherein the nanostructures and the antigen proteins are genetically fused such that they are both present in a single polypeptide and such that the antigen proteins can be displayed on the exterior of the nanostructure (column 43). King et al. further teach multiple polynucleotides encoding mixed nanostructures which display two or more antigens on the same nanostructure (columns 9, 10, 44). In a similar embodiment King et al. teach a composition comprising multiple polynucleotides encoding nanostructures wherein each nanostructure displays a unique antigen and together they create a mixed population of nanostructures (columns 9, 10, 44).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have incorporated the teachings of King et al. about multiple polynucleotides encoding mixed nanostructures into the nucleic acid composition of Votteler et al. for the benefit of formulating a composition capable of harnessing the advantages of subunit vaccines while increasing the potency and breadth of the vaccine-induced immune response through multivalent display of antigens as taught by King et al.
One of ordinary skill in the art would have had reasonable expectation of success in incorporating the teachings of King et al. to the nucleic acid composition of Votteler et al. given that the methods of cloning and formulating multiple distinct fusion proteins encoding a variety of antigen proteins are well known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Regarding claim 13, it is noted that the amendment was made to overcome the previous objections set forth in the Non-Final Office Action mailed on 08/11/2025. No new limitations were introduced in the amendment filed on 11/11/2025. Accordingly, the rejection under 35 U.S.C. 103 set forth in the previous Non-Final Office Action mailed on 08/11/2025 still applies to amended claim 13. As previously explained, King et al. teach multiple polynucleotides encoding mixed nanostructures which display two or more antigens on the same nanostructure (columns 9, 10, 44) and in a similar embodiment King et al. teach a composition comprising multiple polynucleotides encoding nanostructures wherein each nanostructure displays a unique antigen and together they create a mixed population of nanostructures (columns 9, 10, 44).
Regarding claim 14, it is noted that the amendment was made to overcome the previous objections set forth in the Non-Final Office Action mailed on 08/11/2025. No new limitations were introduced in the amendment filed on 11/11/2025. Accordingly, the rejection under 35 U.S.C. 103 set forth in the previous Non-Final Office Action mailed on 08/11/2025 still applies to amended claim 14. As previously explained, King et al. teach a nanostructure comprising two antigen proteins from the same pathogen, for example, two influenza HA proteins from different strains which bear only a couple of differential amino acid residues and therefore share over 70% sequence identity to one another. Similar embodiments are taught by King et al. involving HIV-1 gp140 proteins and Dengue virus E proteins (column 10).
Regarding claim 15, it is noted that the amendment was made to overcome the previous objections set forth in the Non-Final Office Action mailed on 08/11/2025. No new limitations were introduced in the amendment filed on 11/11/2025. Accordingly, the rejection under 35 U.S.C. 103 set forth in the previous Non-Final Office Action mailed on 08/11/2025 still applies to amended claim 15. As previously explained, King et al. teach antigen proteins from different infectious agents, for example, influenza HA proteins from different strains, HIV-1 gp140 proteins, and Dengue virus E proteins (column 10).
Accordingly, claims 12-15 were prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
(Previous rejection, maintained and modified as necessitated by amendments as to claims 11, 17 and 18) Claims 11, 17 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Votteler J et al., as applied to claims 1-4, 8-10 and 16 above, in view of Moore et al. (prior art of record).
See claims 11, 17 and 18 as submitted on 11/11/2025.
Regarding claim 17, it is noted that the amendment was made to overcome the previous rejections under 35 U.S.C. 112(b), second paragraph set forth in the Non-Final Office Action mailed on 08/11/2025. No new limitations were introduced in the amendment filed on 11/11/2025. Accordingly, the rejection under 35 U.S.C. 103 set forth in the previous Non-Final Office Action mailed on 08/11/2025 still applies to amended claim 17. As previously explained, Votteler et al. teach the amino acid composition of claim 1. Votteler et al. further teach vectors comprising the polynucleotide of claim 1 (Supplementary Table 3). Votteler et al. do not teach wherein the nucleic acid composition of claim 1 comprises mRNA.
However, Moore et al. teach compositions comprising mRNAs having chemical and/or structural modifications, including RNA elements and/or modified nucleotides, which can be translated efficiently in cells given that, unlike DNA which is subject to leaky scanning potentially resulting in the bypass of the desired initiation codon that begins the open reading frame, an mRNA molecule allows for promoting translation of only one open reading frame encoding a desired translation product (Abstract, pages 1, 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have incorporated the teachings of Moore et al. about the efficient translation of mRNAs into the nucleic acid composition of Votteler et al. for the benefit of formulating a composition comprising mRNA, wherein the mRNA molecule promotes translation of only one open reading frame encoding a desired translation product as taught by Moore et al.
One of ordinary skill in the art would have had reasonable expectation of success in incorporating the teachings of Moore et al. about the efficient translation of mRNAs to the nucleic acid composition of Votteler et al. given that the methods of formulating mRNAs for delivery into a cell are well known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Regarding claim 18, no new limitations were introduced in the amendment filed on 11/11/2025. Moore et al. further teach the mRNA is formulated in a lipid nanoparticle (LNP) comprising one or more of an ionizable cationic lipid, a non-cationic lipid, a sterol, and a PEG-modified lipid (page 131).
Regarding claim 11, no new limitations were introduced in the amendment filed on 11/11/2025. Votteler J et al. disclose the composition of claim 9, Moore et al. further teach the APs comprising antigenic peptides comprising tumor-associated antigens (pages 118, 207).
Accordingly, claims 11, 17 and 18 were prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
(New rejection, necessitated by the addition of new claim 21) Claims 21 is rejected under 35 U.S.C. 103 as being unpatentable over Votteler J et al., as applied to claims 1-4, 8-10 and 16 above, in view of US patent 10501733 B2 to King et al. filed on 02/28/2019 (See PTO-892: Notice of References Cited.)
Regarding claim 21, Votteler et al. teach the amino acid composition of claim 1. Votteler et al. further teach a recruitment of the Endosomal Sorting Complexes Required for Transport (ESCRT) machinery element (an ESCRT-recruiting domain ERD, as recited in claims 1 and 21) to allow proper ESCRT recruitment (Abstract, pages 1, 2; Figs. 1A-C).
Votteler et al. do not teach and amino acid sequence for said ERD.
However, King et al. teach multimeric assemblies, including multiple oligomeric structures wherein each oligomeric structure comprises multiple proteins and an ESCRT-recruiting motif (Abstract, column 2). King et al. further teach amino acid sequences for said ESCRT-recruiting motif. One such sequence shares 100% identity to instant SEQ ID NO: 23. See alignment below (Qy is instant SEQ ID NO: 23, and Db is King et al.’s SEQ ID NO: 171).
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It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have incorporated the sequence for an ESCRT-recruiting motif taught by King et al. for the benefit of ensuring proper ESCRT-recruiting by a known and tested sequence into the nucleic acid composition of Votteler et al. See MPEP 2144.07. 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).
One of ordinary skill in the art would have had reasonable expectation of success in incorporating the ESCRT-recruiting motif sequence of King et al. to the nucleic acid composition of Votteler et al. given that the methods of cloning and formulating multiple distinct fusion proteins encoding a variety of antigen proteins are well known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Accordingly, the limitations of claim 21 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 11/11/2025 have been fully considered but they are not persuasive.
Applicant contends on page 14 of the Remarks submitted on 11/11/2025:
“Regarding the ERD of claim 4, the Applicant respectfully notes that the application as filed provides description and data supporting ERDs having at least 70% sequence identity with the human CEP55 EABR. In fact, EABR sequences from species having a sequence identity of less than 70% with human CEP55 EABR were used successfully for generation of enveloped nanoparticles. For example, chicEABRmut1 and chicEABRmut2 have a sequence identity of less than 70% with human EABRmmi (CEP55180-213), and yet "[a]ll constructs (e.g., fusion protein constructs) generated S-EABR NPs, and the two constructs based on the chicken EABR domain, chicEABRmut1 and chicEABRmut2, improved S-EABR NP production compared to the human EABRmin1 construct (FIG. 2)" (emphasis added, paragraph [0225]).”
In response:
The instant rejection is in view of instant claim language. Although the claims are interpreted in light of the Specification, limitations from the Specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The instant claims do not mention nor require any limitation in regards to chicEABRmut1 and chicEABRmut2 nor species having a sequence identity of less than 70% with human CEP55 EABR. As explained previously and above, the Specification has failed to sufficiently describe the structural features that must be retained by members of the claimed genera as to establish a structure-function relationship with respect to recruitment of proteins via the ESCRT pathway, as required by claim 4 Accordingly, the information provided in reference to the chicEABRmut1 and chicEABRmut2 constructs are of no relevance to overcome the rejections of record.
Applicant contends on page 15 of the Remarks submitted on 11/11/2025:
“Votteler fails to teach or suggest a fusion protein comprising an antigenic polypeptide. The Office Action cites Figs. 1A-C of Votteler, but this provides that "EPN release requires three functional elements" and does not mention an antigenic polypeptide (or VSV glycoprotein). The Office Action also cites the Votteler Abstract, but this provides that "EPNs that incorporate the vesicular stomatitis viral glycoprotein can fuse with target cells and deliver their contents" - accordingly VSV glycoprotein (VSV-G) is a component that can be incorporated into an EPN to enable fusion with target cells. Rather than being a component of a fusion protein, Votteler discloses that the VSV glycoprotein is encoded by a separate plasmid and co-transfected with a plasmid encoding the fusion protein with the three aforementioned elements (See, e.g., Extended Data Figure 7a, reproduced below; See also "EPN-01 delivery assay" under the Methods section). Accordingly, Votteler fails to teach (or suggest) a fusion protein comprising an antigenic polypeptide and an ERD.
In response:
Applicant’s explanation regarding the co-expression of a VSV-G construct is acknowledged. However, Votteler et al. already teach fusion of viral proteins with antigenic properties to the construct of claim 1. For example, Extended Data Fig. 8 shows a variety of functional elements and fusion protein architectures. Among the fusion proteins of Votteler et al. are those comprising for example, a fragment of an HIV-1 Gag protein or a fragment of an Ebola virus VP40 protein, both of which are heterologous to the host and thus retain immunogenic properties. Accordingly, Votteler et al. provide clear teachings that additional proteins can be incorporated to the construct of claim 1. To reiterate, the instant rejection is in view of instant claim language. Although the claims are interpreted in light of the Specification, limitations from the Specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Claim 1 merely requires an antigenic polypeptide. As such, absent evidence to the contrary, the disclosure of Votteler et al. meets the limitations of the claim.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARLENE V BUCKMASTER whose telephone number is (703)756-5371. The examiner can normally be reached M-F 8-5.
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/MARLENE V BUCKMASTER/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672