DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed 1/14/26 in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/15/25 has been entered.
Claims 1, 6, 25, 27, 33, 38, 64, 72, 90-91 have been amended.
Claims 1, 6-7, 9, 12, 23, 25, 27, 33, 38, 64, 72, 76-78, 80, and 90-91 are pending.
Claims 12 and 77-78 and 80 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention. Claims 27, 33, and 90-91 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to non-elected species.
Claims 1, 6-7, 9, 23, 25, 38, 64, 72, and 76 are being acted upon.
The prior art rejections over US 2019/0202892 are withdrawn in view of Applicant’s statement invoking common ownership under the 102(b)(2) exception.
The previous grounds of rejection are withdrawn in view of Applicant’s claim amendments, and the following are new grounds of rejection. Any arguments relevant to the new grounds of rejection will be addressed below.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 6-7, 9, 23, 25, 38, 64, 72, and 76 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is directed to a method of inducing “an immune response against Mycobacterium tuberculosis” comprising administering a combination of: (i) an EV comprising IL-12; and (ii) a Mycobacterium tuberculosis antigen. The claim further recites that “the induction of the immune response of the EV” is increased at least about 2-fold. It is not clear whether the recitation of “the immune response of the EV” is intending to modify “an immune response against M. tuberculosis” from the preamble. It is noted that the EV comprises IL-12, and is not required to comprise the M. tuberculosis antigen (the antigen could be in the exosome, but it could also be separate from the exosome). Therefore, the immune response of “the EV” is not necessarily specific to the M. tuberculosis antigen. In other words, there is insufficient antecedent basis for “the immune response of the EV” in the claim, since the preamble recites “an immune response against M. tuberculosis”. This renders the claim indefinite. The claim is further indefinite in the recitation that “the immune response” is against one or more epitopes of M. tuberculosis, is a CD4 or CD8 T cell response, or both CD4 and CD8 T cell response, or a combination thereof. It is unclear if the limitation regarding the type of immune response is intended to apply to the preamble, or to the immune response of the EV that is increased by at least 2 fold. This leads to ambiguity in the claim scope. For example, do the claims require that “the immune response of the EV” that is increased by at least 2 fold, also be an immune response against one or more epitopes of M. Tuberculosis, a CD4 T cell response, a CD8 T cell response, or both CD4/CD8 T cell response? Would the claim encompass other types of immune responses induced more than two fold by the IL-12 EV, and the further limitations defining the type of immune response would apply to the preamble? For example, would a method wherein the IL-12 EV induces at least two fold increase in a dendritic cell immune response, and wherein the method also induces an 1.5 fold increase in a CD4 T cell response to M. tuberculosis be within the scope of the claims or not.
Claim 1 is indefinite in the recitation of “about”. The term “about” in claim 1 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, and the specification does not provide a standard for ascertaining the requisite degree. The specification in paragraph 62 states that the term about is used to mean approximately, roughly, or around, and gives exemplary embodiments, wherein about can be, e.g. 10 percent up or down. However, this is not a limiting definition, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 6-7, 9, 23, and 76 is/are rejected under 35 U.S.C. 103 as being unpatentable over JP 2017-101012 (as evidenced by an attached translation), in view of Zhang, 2010 and Cheng, 2013 (all of record), as evidenced by Dooley 2021.
The ‘012 publication teaches exosome formulations for treating Mycobacteria tuberculosis infection or for treating a tumor comprising an M. tuberculosis antigen (see claims and disclosure). The ‘012 publication teaches that the antigen can be ESAT-6 from Mycobacterium tuberculosis, which inherently would have at least 3 amino acids from SEQ ID NO: 370. The ‘012 publication teaches that the exosomes induce a T cell immune response against the ESAT-6 antigen (see page 4 of the translation and Fig. 4, in particular). Regarding the limitation that the EV comprises a PTGRN scaffold moiety, this is an inherent/latent property of exomes as evidenced by Dooley, 2021 (see pages 1729-1730, PTGFRN is a scaffold protein abundant in exosome from a variety of cell types).
The reference differs from the claimed invention in that it does not explicitly teach that the exosomes comprises IL-12.
Zhang teaches tumor derived exosomes comprising IL-12, wherein the IL-12 is anchored to the exosome surface by GPI. Zhang teach that the exosomes also comprise an antigen, and that the IL-12 exosomes induce antigen specific T cell responses (see page 139, in particular). Zhang teaches that the IL-12 exosomes increases antigen specific T cell responses at least two fold compared to IL-12 alone (i.e. without an EV, see Fig. 7, in particular). Zhang teaches that exosomes contain antigens that trigger antigen specific T cells responses (see page 133-134). Zhang explains that IL-12 is a critical cytokine that plays an essential role in induction of T cell response driving induction of CTL (i.e. CD8) T cells and driving differentiation of TH1 cells (i.e. CD4 T cells), see page 133 and 139, in particular. Zhang teaches that IL-12 can be administered systemically, but it has a very short half-life and causes side effects, and recent research has focused on the use as an adjuvant for vaccination (See page 133 and 139, in particular). Zhang teaches that anchoring IL-12 to exosomes is a good way to enhance the immunogenicity of exosome based immunotherapy (See page 134, in particular). Zhang also teaches that the IL-12 exosomes increase IFN-gamma production of T cells to higher levels than conventional exosomes or IL-12 alone (i.e. without an EV, see Fig. 6, in particular).
Cheng teaches that exosomes carrying M. tuberculosis antigens can induce antigen specific CD4 and CD8 T cell responses and that induction of Th1 responses and IFN-gamma is important for controlling M. Tuberculosis infection.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to include IL-12 as taught by Zhang, in the exosomes of the ‘012 publication. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because Zhang teaches that the IL-12 in exosomes increase antigen specific T cells responses. Thus, the ordinary artisan would expect that including IL-12 in the exosomes of the ‘012 publication would function to increase the antigen specific T cell response to the antigens in the exosomes (i.e. ESAT-6). Additionally, as induction of TH1 immunity and IFN-gamma production was known as a therapeutic for tuberculosis, as taught by Cheng, the ordinary artisan would also be motivated to include IL-12 in the exosome of the ‘012 publication to enhance treatment outcomes by inducing essential IFN-gamma, and administration via exosomes as opposed to systemic administration would be selected to avoid the problems due to systemic delivery IL-12 taught by Zhang. Furthermore, the ordinary artisan would expect to induce both CD4 and CD8 antigen specific T cell response, since Cheng teaches that exosomes carrying M. Tuberculosis antigens inducing antigen specific CD4 and CD8 T cells.
Claims 1, 6-7, 9, 23, and 76 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rossowska, Feb. 2019, in view of JP 2017-101012 (as evidenced by an attached translation, of record), as evidenced by Dooley 2021.
Rossowska teach a method of inducing an anti-tumor response comprising administering to a subject exosomes comprising IL-12 (See pages 7-9, in particular). Regarding the limitation that the EV comprises a PTGRN scaffold moiety, this is an inherent/latent property of exomes as evidenced by Dooley, 2021 (see pages 1729-1730, PTGFRN is a scaffold protein abundant in exosome from a variety of cell types).
Regarding the limitation that the induction of an immune response of the EV is increased by at least about 2 fold compared to IL-12 without an EV, this is a latent property of including IL-12 in an EV. In other words, the IL-12 EV of Rossowska is identical to that of the instant claims, and functional properties thereof in inducing an immune response would be inherent.
The reference differs from the claimed invention in that it does not explicitly teach administering a Mycobacterium tuberculosis antigen..
The ‘012 publication teaches including an M. tuberculosis antigen, such as ESAT-6, in exosomes and that it acts as a danger signal that enhances anti-tumor immune response. Said ESAT-6 from Mycobacterium tuberculosis, inherently would have at least 3 amino acids from SEQ ID NO: 370. The ‘012 publication teaches that ESAT-6 is highly antigenic and the exosomes induce a T cell immune response against the ESAT-6 antigen which enhances the anti-tumor effect (see page 4 of the translation and Fig. 4, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to include ESAT-6 antigen as taught by the ‘012 publication, in the exosomes of the Rossowska. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because the ‘012 publication teaches that doing so induces antigenic responses to the tuberculosis antigens that act as a danger signal to enhance anti-tumor immune response (i.e. the subjects are “in need of” induction of an immune response against said M. tuberculosis because it increase the anti-tumor immune response) .
Claim 25, 38, 72 is/are rejected under 35 U.S.C. 103 as being unpatentable over JP 2017-101012, in view of Zhang, 2010 and Cheng, as applied to claim 1, above, and further in view of US2019/0060483 (all of record).
The combined teaches of the ‘012 publication, Zhang and Cheng are descried above.
They do not teach that IL-12 is linked to PTGFRN scaffold.
The ‘483 publication teaches surface engineered exosomes comprising a fusion protein between a therapeutic peptide ligand and a protein such as PTGFRN ( see pages 8-9, in particular). The ‘483 publication teaches that the exosomes are advantageous since the proteins are more highly enriched on the cell surface with more controlled biological activity as compared to using a GPI anchor (see page 9, in particular). The ‘483 publication teaches attaching proteins by a linker (see paragraph 30 and 104, in particular). The ‘483 publication also teaches said scaffold protein having SEQ ID NO: 33, which is identical to SEQ ID NO: 33 of the instant application (see page 13, in particular).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the invention was made to apply the teachings of the ‘483 publication regarding the use of PTGFRN as a scaffold moiety, in place of the GPI anchor in the exosomes made obvious by the ‘012 publication and Zhang. One of ordinary skill in the art at the time the invention was made would have been motivated to substitute the GPI anchor with the PTGFRN scaffold moiety, since the ‘483 publication teaches that it allows for more highly enriched cell surface expression with more controlled biological activity as compared to using a GPI anchor.
Claims 1, 6-7, 9, 23, 25, 38, 72, and 76 is/are rejected under 35 U.S.C. 103 as being unpatentable over JP 2017-101012 (as evidenced by an attached translation), in view of Zhang, 2010, Cheng, 2013, and Dooley, April 1, 2019 (all of record).
The ‘012 publication teaches exosome formulations for treating Mycobacteria tuberculosis infection or for treating a tumor comprising an M. tuberculosis antigen (see claims and disclosure). The ‘012 publication teaches that the antigen can be ESAT-6 from Mycobacterium tuberculosis, which inherently would have at least 3 amino acids from SEQ ID NO: 370. The ‘012 publication teaches that the exosomes induce a T cell immune response against the ESAT-6 antigen (see page 4 of the translation and Fig. 4, in particular). Regarding the limitation that the EV comprises a PTGRN scaffold moiety, this is an inherent/latent property of exomes as evidenced by Dooley, 2021 (see pages 1729-1730, PTGFRN is a scaffold protein abundant in exosome from a variety of cell types).
The reference differs from the claimed invention in that it does not explicitly teach that the exosomes comprises IL-12.
Zhang teaches tumor derived exosomes comprising IL-12, wherein the IL-12 is anchored to the exosome surface by GPI. Zhang teach that the exosomes also comprise an antigen, and that the IL-12 exosomes induce antigen specific T cell responses (see page 139, in particular). Zhang teaches that the IL-12 exosomes increases antigen specific T cell responses at least two fold compared to IL-12 alone (i.e. without an EV, see Fig. 7, in particular). Zhang teaches that exosomes contain antigens that trigger antigen specific T cells responses (see page 133-134). Zhang explains that IL-12 is a critical cytokine that plays an essential role in induction of T cell response driving induction of CTL (i.e. CD8) T cells and driving differentiation of TH1 cells (i.e. CD4 T cells), see page 133 and 139, in particular. Zhang teaches that IL-12 can be administered systemically, but it has a very short half-life and causes side effects, and recent research has focused on the use as an adjuvant for vaccination (See page 133 and 139, in particular). Zhang teaches that anchoring IL-12 to exosomes is a good way to enhance the immunogenicity of exosome based immunotherapy (See page 134, in particular). Zhang also teaches that the IL-12 exosomes increase IFN-gamma production of T cells to higher levels than conventional exosomes or IL-12 alone (i.e. without an EV, see Fig. 6, in particular).
Dooley teaches that PTGFRN can be used to display IL-12 in exosomes by linking (via a linker) IL-12 to PTGFRN scaffold protein (see Fig. 8A). Dooley teaches that said IL-12 exosomes induce durable IFN-gamma responses in vivo, inducing more than a two-fold increase in IFN-gamma immune response as compared to IL-12 not in exosomes (see Fig. 9 C). Dooley teach that the use of PTGFRN in surface display of therapeutic proteins is advantageous since it results in a high density surface display of bioactive molecules that enables production of potent exosomes.
Cheng teaches that exosomes carrying M. tuberculosis antigens can induce antigen specific CD4 and CD8 T cell responses and that induction of Th1 responses and IFN-gamma is important for controlling M. Tuberculosis infection.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to include IL-12 as taught by Zhang and Dooley, in the exosomes of the ‘012 publication. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because Zhang and Dooley teach that the IL-12 in exosomes increase antigen specific T cells responses and induces durable IFN-gamma responses in vivo. Thus, the ordinary artisan would expect that including IL-12 in the exosomes of the ‘012 publication would function to increase the antigen specific T cell response to the antigens in the exosomes (i.e. ESAT-6). Additionally, as induction of TH1 immunity and IFN-gamma production was known as a therapeutic for tuberculosis, as taught by Cheng, the ordinary artisan would also be motivated to include IL-12 in the exosome of the ‘012 publication to enhance treatment outcomes by inducing essential IFN-gamma, and administration via exosomes as opposed to systemic administration would be selected to avoid the problems due to systemic delivery IL-12 taught by Zhang. Furthermore, the ordinary artisan would expect to induce both CD4 and CD8 antigen specific T cell response, since Cheng teaches that exosomes carrying M. Tuberculosis antigens inducing antigen specific CD4 and CD8 T cells. Regarding claim 38, it would be obvious to use a human PTGFRN for compatibility with humans, and having a sequence of SEQ ID NO: 33 or having 80% identity to SEQ ID NO: 1 would be latent property thereof.
Claim 64 is/are rejected under 35 U.S.C. 103 as being unpatentable over JP 2017-101012, in view of Zhang, 2010 (of record) and Cheng, as applied to claim 1, OR over JP 2017-101012, Zhang, 2010, Cheng, 2013, and Dooley, above, and further in view of US2019/0060483, Arima, March 2019, and Woodworth, 2006 (all of record).
The combined teaches of the ‘012 publication, Zhang, Cheng, (and Dooley) are descried above.
They do not teach that the IL-12 is linked to the PTGFRN scaffold o and the M. tuberculosis antigen is linked to the scaffold on the luminal surface of the exosome.
The ‘483 publication teaches surface engineered exosomes comprising a fusion protein between a therapeutic peptide ligand and a protein such as PTGFRN (i.e. a scaffold moiety X, see pages 8-9, in particular). The ‘483 publication teaches that the exosomes are advantageous since the proteins are more highly enriched on the cell surface with more controlled biological activity as compared to using a GPI anchor (see page 9, in particular). The ‘483 publication teaches attaching proteins by a linker (see paragraph 30 and 104, in particular). The ‘483 publication also teaches said scaffold protein having SEQ ID NO: 33, which is identical to SEQ ID NO: 33 of the instant application (see page 13, in particular). The ‘483 publication also teaches that PTGFRN can be used to simultaneously express two different heterologous proteins by fusion to the N- and C terminus resulting in the proteins being displayed on the exosome surface and lumen, respectively (see pages 10-11, and paragraph 233, in particular).
Arima teach methods of loading antigen proteins into exosomes, wherein the antigens can be linked to another protein (i.e. a scaffold moiety) that allows for localization of the antigen to the inner surface or outer surface of the exosome. Arima teach that loading using the inner surface is advantageous since it protects the antigen from degradation allowing more efficient transfer to antigen presenting cells and is effective for immunotherapy and enhances induction of CD8 T cell responses (see pages 2313-2314, in particular).
Woodworth teaches that CD8 T cells are required for optimum host defense against M. tuberculosis infection.
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the invention was made to apply the teachings of the ‘483 publication regarding the use of PTGFRN as a scaffold moiety, to the exosomes made obvious by the ‘012 publication and Zhang (or the ‘012 publication, Zhang, and Dooley). One of ordinary skill in the art at the time the invention was made would have been motivated to substitute the GPI anchor with the PTGFRN scaffold moiety, since the ‘483 publication teaches that it allows for more highly enriched cell surface expression with more controlled biological activity as compared to using a GPI anchor.
Furthermore, the ordinary artisan would be motivated to linked the ESAT6 antigen to the inner surface as taught by Arima. The ordinary artisan would be motivated to do so since Arima teach that it protects antigen from degradation allowing more efficient transfer to antigen presenting cells, is effective for immunotherapy and enhances induction of CD8 T cell responses, which are required for host defense against M. tuberculosis infection, as taught by Woodworth. Furthermore, one could conveniently use the scaffold moiety of the ‘483 publication for both surface display of IL-12 and internal linkage of the antigen as a matter of convivence by expression as a single fusion protein, since the ‘483 publication teaches that PTGFRN can be used to simultaneously express two different heterologous proteins by fusion to the N- and C terminus resulting in the proteins being displayed on the exosome surface and lumen, respectively.
Applicant’s arguments filed 12/15/25 have been fully considered, but they are not persuasive.
Applicant argues that Figs 3-5 of the instant application show induction of CD4 and CD8 T cell responses. Applicant argues that Zhang in Fig. 6 does not show a two fold improvement using IL-12 in exosomes, as recited in the present claims.
Figure 6 examined the ability of the IL-12 exosomes, or IL-12 alone to stimulate IFN-gamma production by T cells in vitro. However, in Figure 7, Zhang also examines the effect of the exosomes on antigen specific T cell response, wherein the IL-12 exosomes increase antigen specific T cells more than 2 times as compared to IL-12 not in exosomes. This would be within the scope of the present claims which recite induction of an immune response of the EVs by at least about 2 fold compared to IL-12 without an EV.
To the extent that Applicant argues that the results in the specification demonstrates unexpected results, it is noted that evidence of unexpected results must be commensurate in scope with the claims. None of the data in Figs. 3-5 involve administration a mycobacteria tuberculous antigen, as recited in the present claims (thus these results would not be commensurate in scope with the instant claims). Furthermore, the examples do not even specify what the IL-12 exosomes are (do the exosomes even comprise PTGRRN?). For example, if the exosomes in the examples comprise surface IL-12 linked to PTGFRN, this would not be commensurate in scope with the instant claims which encompass IL-12 not linked to PTGFRN, or linked to the interior surface of the exosome.
Furthermore, enhanced immune responses is an art recognized expected benefit of IL-12 administration in exosomes as compared to recombinant IL-12. For example, Zhang teaches that IL-12 exosomes increase antigen specific T cell responses at least 2 fold compared to IL-12 not in an exosome (Fig. 7). See also Dooley, 2019 (of record), which teaches that IL-12 in an exosome is superior to soluble IL-12 in inducing IFN-gamma production.
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 6-7, 9, 23, 25, 38, 64, 72, and 76 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 10,723,782, or over claims 1-18 of US 12,030,924, or over claims 1-20 of US 12,331,100, in view of Ha, 2006, JP 2017-101012, Zhang, 2010, Cheng, 2011, Arima, March 2019, and Woodworth, 2006.
The patents claim a composition comprising an extracellular vesicle comprising a fusion comprising PTGFRN fused to IL-12 that functions in immunomodulation. The patents claim that the vesicle is an exosome.
As taught by Ha, IL-12 can be co-administered with M. tuberculosis antigens, such as ESAT-6, to induce an immune response against M. tuberculosis. Zhang also teaches that exosomes comprising IL-12 can increase antigen specific immune response. Therefore, it would be obvious to administer the immunomodulating IL-12 exosomes claimed in the patents, in combination with a M. tuberculosis antigen to increase antigen specific immune response, as taught by Ha and Zhang (having PTGRN is an inherent property of exosomes for the reasons set forth above). Furthermore, it would be obvious to include a tuberculosis antigen in the exosomes as taught by the ‘012 publication, Zhang, and Cheng for the same reason set forth above. Furthermore, linking an antigen to the luminal membrane and the use of PTGRN would also be obvious based on the teachings of the ‘483 publication, Arima, and Woodworth for the same reasons set forth above.
Claims 1, 6-7, 9, 23, 25, 38, 64, 72, and 76 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19/220,569, or claims 1-4, 7, 14-15, 18-20, 23-2427-28, 32, 34, 37, 41 of Application No. 17/763,973, or claims 1, 8, 10,13-16, 18, 20, 41, 46 of Applicant No. 18/042,068, in view of JP 2017-101012, Cheng 2013, US2019/0060483, Arima, March 2019, and Woodworth, 2006.
The applications all claim methods of treating cancer comprising administering a composition comprising an extracellular vesicle comprising a fusion comprising PTGFRN (i.e. scaffold) fused to IL-12. The patents claim that the vesicle is an exosome.
Although the applications do not claim administering an antigen of M. tuberculosis, it would be obvious to do so based on the teachings of the ‘012 publication. The ‘012 publication teaches including M. tuberculosis antigens in cancer treating exosomes, and that doing so is advantageous since it provides an external danger signal that induces a response against the M. tuberculosis antigens that serves to enhance the anti-tumor immune response (i.e. the patients are “in need of” induction of an immune response against said M. tuberculosis because it increase the anti-tumor immune response). Furthermore, linking an antigen to the luminal membrane would also be obvious based on the teachings of the ‘483 publication, Arima, and Woodworth for the same reasons set forth above.
These are provisional nonstatutory double patenting rejections.
Applicant argues that present application was restricted into two groups, products and methods, and that therefor the pending claims are patentably distinct from the claims in the conflicting patents.
While the restriction would prohibit double patenting under 35 U.S.C. 121 on any application filed as a DIV in response to the restriction, the conflicting patents were not filed as a DIV of the current application and the 121 prohibition does not apply.
No claim is allowed.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644