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 .
Election/Restrictions
Applicant’s election without traverse of Group I, directed to a vaccine preparation, and Species group A, directed to the antigen being a foreign antigen from a microorganism, in the reply filed on 06/09/2026 is acknowledged.
Claims 21, 23, 25, 27, 28, 30, 41 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group of invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/09/2026.
Claims 14 and 37 is/are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/09/2026.
Claims status
Amendments filed 06/09/2026 are entered. Claims 1, 2, 4, 5, 8, 14, 16, 18, 20, 21, 23, 25, 27, 28, 30, 41-44 are pending.
Claims 14, 21, 23, 25, 27, 28, 30, 37, and 41 are withdrawn.
Claims 1, 2, 4, 5, 8, 16, 18, 20, 42-44 are under examination.
Priority
This application is a 371 application, filed 02/05/2024, of PCT application PCT/US2022/040243, filed 08/12/2022, which claims priority benefits from Provisional No. 63233190, filed 08/13/2021. The effective filing date of this application is 08/13/2021, the filing date of Provisional No. 63233190.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 02/05/2024, 02/272024, and 12/04/2024 is/are being considered by the examiner.
Claim Objections
Applicant is advised that should claim 20 be found allowable, claim 44 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 1 is 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.
In claim 1, due to sentence structure, it is unclear whether the limitation “that has been genetically modified for an improved therapeutic outcome” modifies only the endogenous antigen or if it also modifies the foreign antigen.
Additionally, the term “improved” in claim 1 is a relative term which renders the claim indefinite. The term “improved” 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. It is unclear what the baseline or comparison counterpart is for the claimed therapeutic outcome improvement. Is the comparison between a vaccine where an antigen that has been genetically modified, resulting in an improved therapeutic outcome, and the same antigen that has not been genetically modified for improved therapeutic outcome?
The claim will be interpreted to mean that only the endogenous antigen option has been genetically modified, resulting in an improved therapeutic outcome compared to the therapeutic outcome of endogenous antigens that have not been genetically modified for improved therapeutic outcome.
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 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.
Claim(s) 1, 2, 5, 8, 16, 20, 42, and 44 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kwon (Kwon et al, WO 2020/037303 Al, published 2020) in view of Dyall (Dyall et al, Lentivirus-transduced human monocyte-derived dendritic cells efficiently stimulate antigen-specific cytotoxic T lymphocytes, published 2001).
Regarding claim 1, Kwon teaches extracellular blebs from antigen presenting cell, e.g. dendritic cells (p. 79, para. 00203), that display a foreign antigen (i.e. SIINFEKL or AAV) (p. 79, para. 00204) on the surface of the bleb (p. 79, para. 00208) and encapsulated within the bleb (e,g, Figure 27 and p. 14, para. 0038), wherein the extracellular blebs are produced from an antigen presenting cell by treating the antigen presenting cell with a blebbing agent (e.g. N-ethylmaleimide (NEM)) (p. 14, para. 0038 and p. 80, para. 00208). Kwon teaches these extracellular blebs displaying the antigens could be used in a vaccine preparation to provide protective immunity against the antigen displayed by the extracellular blebs (p. 85, para. 00219 – p. 86, para. 00220). In summary, Kwon teaches a method of making the claimed product by stimulating the antigen presenting cell with the target antigen to generate the antigen presenting cell displaying the antigen.
Kwon does not explicitly teach the blebs has been genetically engineered, using a viral vector, to express the antigen.
However, Dyall teaches a method of genetically engineering a dendritic cell (DC), which is an antigen presenting cell, to stably express a desired antigen molecule, from a pathogen or tumor, by transduction of the antigen expression vector via a lentivirus; and further provides a motivation for doing so over the method of antigen stimulation of the cell taught by Kwon (Abstract). Specifically, this approach enables high and sustained antigen expression levels, and the transduced DCs were at least as efficient at antigen presentation to T cells as antigen-presenting DCs made from being pulsed with the same antigen peptide (Abstract).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to use the method of making stably expressed antigen presenting DCs taught by Dyall to make the extracellular blebs taught by Kwon, due to the advantages of high and stable antigen expression.
One skilled in the art, before the effective filing date of the instant application, would be motivated to create a more homogenous antigen display on the extracellular blebs to create a homogenous vaccine formulation that can yield more predictable results batch by batch.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success of generating extracellular blebs that comprise of these antigens even more efficiently for the reasons provided above, and that these antigens further act as an immunogen in a vaccine because the antigens displayed by the transduced DCs are shown to have at least the same ability to stimulate T cells as the pulsed-peptide DCs.
Claims 2, 5, 8, 16, 20, 42, and 44 depend on claim 1. The teachings of the references regarding claim 1 are incorporated in its entirety for the dependent claims and discussed further below, as is relevant for each claim.
Regarding claim 2, Kwon (p. 79, para. 00203) and Dyall (Abstract) further teach the antigen presenting cell is a dendritic cell.
Regarding claim 20 and 44, Kwon teaches that the bone marrow-derived dendritic cells (BMDC) express CD11c, which is a specific marker of BMDCs (p. 81, para. 00208) and Dyall teaches their mature monocyte-derived DC exhibit CD80 expression (Figure 2).
Regarding claim 5, Dyall teaches the antigen presenting cell is a human primary cell, i.e. primary human monocyte-derived dendritic cell from human peripheral blood (p. 115, col. 2, section: Generation of dendritic cells).
Regarding claim 8, Dyall teaches the foreign antigen is from a pathogenic influenza virus (Abstract and p. 116, section: Peptide synthesis).
Regarding claims 16 and 42, Dyall teaches the viral vector is a lentivirus (p. 115, col. 1, section: Lentiviral vector construction and production).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to use a human monocyte-derived dendritic cell from human peripheral blood since they are natural antigen presenting cells for humans and producers of extracellular vesicles carrying an antigen, providing reasonable expectation of success that these cells will achieve the required claimed functions, bleb and present an antigen on the bleb to humans, since it already has all the required cellular machinery. One would be motivated to choose cells from end target, i.e. humans, to minimize any species-specific differences that could interfere with antigen presentation and immune response.
It would have been obvious and motivated to one skilled in the art, before the effective filing date of the instant application, to choose a human pathogen that there is a high need to protect against, and one skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success that these human derived antigen presenting cells can present a wide variety of foreign antigens.
It would further be obvious to genetically engineer the cell to stably present the antigen to homogenously produce antigen-presenting extracellular vesicles, and to do so using a common vector for incorporating genetic material into cells, such as a lentivirus. One skilled in the art, before the effective filing date of the instant application, would be motivated to produce homogenously presented antigens to make more efficient vaccines and to do the genetic engineering using a commonly used and effective cell engineering vector. One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success in the lentivirus-mediated genetic engineering as Dyall teaches this same method successfully for human primary cells.
Claim(s) 4 and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kwon (published 2020) in view of Dyall (published 2001), as applied to claim 1 above, and further in view of Paglia (Paglia et al, Immortalized Dendritic Cell Line Fully Competent in Antigen Presentation Initiates Primary T Cell Responses In Vivo, published 1993).
Claim 4 and 18 depends on claim 1. The teachings of the references regarding claim 1 are incorporated in its entirety for the dependent claims and discussed further below, as is relevant for each claim.
Regarding claim 4, Kwon in view of Dyall do not teach immortalizing the antigen presenting cell. Regarding claim 18, Kwon in view of Dyall do not teach the vaccine further comprises an adjuvant.
However, Paglia further teaches immortalized dendritic cells retain most of their morphological, immunophenotypic, and functional attributes, at least enough so as to retain their antigen presentation abilities when pulsed with antigens (Abstract). Paglia further teaches the DC biology can be challenging due to the naturally small numbers of primary cells form tissue, and therefore, the generation of stable cells lines representative of DCs or immortalized DC cells are motivated (p. 1894, col. 1, para. 1-2).
Furthermore, Paglia teaches that antigen-presenting DCs, but not other APCs, can prime T cells without additional adjuvants (p. 1898, col. 1, para. 1) but that purified or recombinant protein antigens typically need an adjuvant (p. 1898, col. 2, para. 3).
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, that an immortalized antigen presenting cell would help enable consistent and more convenient generation of homogenous extracellular blebs than having to start from primary cells each time. Secondly, it would have been obvious to one skilled in the art, before the effective filing date of the instant application, that adding an adjuvant could be beneficial to the antigen-displaying extracellular bleb, as it could act more like a purified or recombinant protein antigen than the full antigen-presenting DC.
One skilled in the art, before the effective filing date of the instant application, would be motivated to take advantage of the convenience and benefits that immortalized cells have over primary cells in producing antigen-presenting extracellular blebs. Secondly, one would be motivated to add the adjuvant for the advantage of supporting the degree of immune response induction against the target antigen.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success that the extracellular blebs will display the desired antigens, as expected from primary or stably-transduced dendritic cells, since these immortalized dendritic cells can also retain their antigen presentation abilities. Secondly, one would have reasonable expectation of success with adding an adjuvant, since this concept is well established in the vaccine preparations.
Claim(s) 43 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kwon (published 2020) in view of Dyall (published 2001), as applied to claim 1 above, and further in view of Mir (Mir et al, Extracellular Vesicles as Delivery Vehicles of Specific Cellular Cargo, published 2020).
Claim 43 depends on claim 1. The teachings of the references regarding claim 1 are incorporated in its entirety for the dependent claims and discussed further below, as is relevant for each claim.
Regarding claim 43, as previously presented, Kwon in view of Dyall teach the claimed vaccine preparation comprising of an influenza antigen, wherein Dyall teaches that the antigen presenting cell can be used to display foreign antigens from pathogens of interest.
Kwon and Dyell do explicitly teach the foreign antigen is SARS-CoV-2.
However, Mir teaches that SARS-CoV-2 is the pathogen causing coronavirus disease 2019 (COVID-19) (p. 7, section: 3.5. Foreign Molecules). Mir teaches that extracellular vesicles (EVs), which are the name of the naturally-occurring counterparts to extracellular blebs, are cargo delivery vehicles (Abstract), and in particular when delivering foreign antigens, can trigger an immune response (p. 7, section: 3.5. Foreign Molecules). Mir further teaches that there was no known connection between SARS-CoV-2 and the EV release pathway published at the time, i.e. it was not known if any component of SARS-CoV-2 gets released in EV’s.
It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to develop a vaccine against the COVID-19 pandemic using a SARS-CoV-2 antigen, and to use the EVs as an antigen delivery method, as taught previously by Kwon in view of Dyall for influenza. More specifically when using EV’s, because it was unknown at the time if antigen pulsed-antigen presenting cells’ EVs would display and encapsulate SARS-CoV-2 antigens, it would have been obvious to one skilled in the art, before the effective filing date of the instant application, to genetically engineer the antigen presenting cells to present the antigen.
One skilled in the art, before the effective filing date of the instant application, would be motivated to ensure the EVs present the SARS-CoV-2 antigen, by transducing the cell to present the antigen in light of the uncertainty at the time whether a SARS-CoV-2 antigen-pulsed APC would produce EVs presenting the SARS-CoV-2 antigen.
One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success that a SARS-CoV-2 antigen could be substituted with the influenza antigen in the preparation taught by Kwon in view of Dyall to yield a vaccine preparation for SARS-CoV-2 because of the versatility and likelihood of success of the lentiviral transduction, with some optimization and correct antigen choice.
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.
Claim(s) 1 2, 5, 8, 16, 20, 42, and 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8-10, 18-21, 26 of U.S. Patent No. US 12296023 B2 (hereafter Patent ‘023) in view of Kwon (Kwon et al, WO 2020/037303 Al, published 2020) and Dyall (Dyall et al, Lentivirus-transduced human monocyte-derived dendritic cells efficiently stimulate antigen-specific cytotoxic T lymphocytes, published 2001).
Patent ‘023 is the patent claims that resulted from reference Kwon. The claims of Patent ‘023 are directed to a vaccine comprising induced extracellular blebs for the prevention of an infection in a subject by an infectious agent, wherein the extracellular blebs are generated by a blebbing agent. The teachings, motivations, and reasonable expectation of success from combining this base extracellular bleb from Patent ‘023 and Kwon with the other references to arrive at the claimed invention is presented in the 35 USC 103 rejections above and incorporated here.
Claim(s) 4 and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8-10, 18-21, 26 of U.S. Patent No. US 12296023 B2 (hereafter Patent ‘023) in view of Kwon (published 2020) and Dyall (published 2001), as applied to claim 1 above, and further in view of Paglia (Paglia et al, Immortalized Dendritic Cell Line Fully Competent in Antigen Presentation Initiates Primary T Cell Responses In Vivo, published 1993).
Claims 4 and 18 depend on claim 1. The teachings of the references regarding claim 1 are incorporated in its entirety for the dependent claims and discussed further below, as is relevant for each claim.
The teachings, motivations, and reasonable expectation of success from combining this base extracellular bleb from Patent ‘023 and Kwon with the other references to arrive at the claimed invention is presented in the 35 USC 103 rejections above and incorporated here.
Claim(s) 43 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8-10, 18-21, 26 of U.S. Patent No. US 12296023 B2 (hereafter Patent ‘023) in view of Kwon (published 2020) and Dyall (published 2001), as applied to claim 1 above, and further in view of Mir (Mir et al, Extracellular Vesicles as Delivery Vehicles of Specific Cellular Cargo, published 2020).
Claim 43 depends on claim 1. The teachings of the references regarding claim 1 are incorporated in its entirety for the dependent claims and discussed further below, as is relevant for each claim.
The teachings, motivations, and reasonable expectation of success from combining this base extracellular bleb from Patent ‘023 and Kwon with the other references to arrive at the claimed invention is presented in the 35 USC 103 rejections above and incorporated here.
Conclusion
No claims are allowed.
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/BONIRATH CHHAY/Examiner, Art Unit 1645 July 24, 2026
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 July 30, 2026
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