DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Restrictions/Elections
Applicant’s election without traverse of Group II, claims 18-19, 21-23, 28-29, 32, and 35 drawn to methods of reducing an antigen specific immune response, in the reply filed on August 13, 2024 is acknowledged.
Status of the Claims
Claims 1, 3-4, 6-7, 10-11, 18-19, 21-23, 28-29, and 32-35 are currently pending. Claims 1, 3-4, 6-7, 10-11, 33-34 are withdrawn from consideration. Claims 18-19, 21-23, 28-29, 32, and 35 are the subject of this Office Action and are under consideration. This is the first Office Action on the merits of the claims.
Withdrawn Claim Rejections
In view of the Applicant’s claim amendments: the previous rejections under 35 U.S.C. 112 are hereby withdrawn.
Maintained 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.
Claims 18-19, 21-23, 28-29, 32, and 35 stand/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Vasu1 in view of Kaneko2.
Regarding claim 18-19, 21-23, 28, 32, Vasu discloses: A composition comprising biodegradable microspheres coupled to antigenic peptides (see in particular: claims 1-8; p. 5 par. 1- “what is needed is a biodegradable microsphere based tolerogenic based antigen presentation system wherein the system is used for the treatment of autoimmune conditions… where T cells specific to antigenic epitopes are involved”; and p. 19 par. 4- “with respect to MHC:antigen complexes coated onto microsomes, antigens include, but are not limited to, self-antigens (e.g., antigenic peptides, of insulin…)”), further comprising a death inducing ligand (i.e., apoptotic signaling molecule) including Fas-ligand (see claims 1-4 and 26-29; reads on instant claims 18-19 and 21); a method for inducing antigen specific tolerance, i.e., reducing an antigen-specific immune response (see abstract- “The herein presented microspheres… can induce antigen specific tolerance”; claim 32 reads on instant claim 18); and a method of treating a patient suffering from an autoimmune disease, comprising administering the composition (see claim 34; reads on instant claims 28 and 32). Regarding claim 29, Vasu discloses wherein the composition is delivered orally, nasally, intravenously, intramuscularly, parenterally, ocularly or subcutaneously (see p. 22). Regarding claim 35, Vasu discloses wherein the biodegradable carrier comprises a polymer, such as polyglycolic acid (PGA), polylactic acid (PLA), or poly (lactic-co-glycolic) acid (PLGA) (see Vasu claims 7-9 and p. 19-20).
The prior art of Vasu differs from the instantly claimed invention as follows: The prior art of Vasu does not expressly disclose coupling the antigenic peptide to the carrier microsphere via the conjugate molecule, ethylene carbodiimide (ECDI). However, Vasu discloses the microspheres may be modified with carboxyl groups and further emphasizes that one of ordinary skill in the art will recognize that cross-linking agents may be used to link various ligands, proteins, and peptides to the surface of a modified microsphere (see p. 5, claim 25, Example 25).
Kaneko teaches: ECDI is a chemical cross-linker that modifies carboxyl groups and has been used to couple antigen to antigen presenting cells (APC) to promote T cell tolerance in several experimental inflammatory or autoimmune disease models and further teaches that there is evidence that ECDI treatment interferes with the capacity of APC to deliver costimulatory signals to T cells and confers the ability to induce reversible antigen-specific CD4+ Th1 cell anergy and apoptosis, with concomitant priming of Th2 cells (see abstract, introduction, particularly at bridge between p. 190-191, and discussion; reads on instant claim 22).
In light of these teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the presently claimed invention in view of the prior art because it merely amounts to: (i) combining prior art elements according to known methods to yield predictable results; the prior art of Vasu suggests incorporating carboxyl groups and cross linking agents (e.g., ECDI, a chemical cross-linker known to modify carboxyl groups, per the teachings of Kaneko) link peptides to the microspheres of their invention, and that doing so is well within the abilities of one with ordinary skill in the art (MPEP 2143(I)(A), (G)); and (ii) use of known technique (e.g., coupling antigen to APC via ECDI to promote T cell tolerance, anergy, and apoptosis in autoimmune disease, as taught by Kaneko) to improve similar methods (e.g., coupling antigen to biodegradable microcarrier, which functions as an artificial APC molecule, as taught by Vasu) in the same way (MPEP 2143(I)(C), (D)). Additionally, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)).
Accordingly, claims 18-19, 21-23, 28-29, 32, and 35 are rejected.
Claim Rejections, Necessitated by Amendment - 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.
Copending Application No. 19/024,886 (PG PUB Np. US20250387461)
Claims 18-19, 21-23, 28-29, 32, and 35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9-11, 13-16, 20, 65, 125-128 of copending Application No. 19/024,886 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other as described below.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). The following rejection is based upon both anticipation and obviousness analyses.
Anticipation analysis: Regarding instant claims 18-19, 28, and 32, the reference application explicitly claims a method of inducing antigen-specific tolerance3 in a subject suffering from or at risk of an autoimmune disease, transplant rejection, or allergy, comprising administering a composition to said subject, wherein the composition comprises an apoptotic body surrogate and a plurality of immunodominant epitopes associated with one or more antigens suspected to cause said diseases (see reference claim 1, 9-11, 13-16, 20, 65, 125-128). Accordingly, instant claims 18-19, 28, and 32 are anticipated by the reference claims.
Obviousness analysis: Although the reference patent doesn’t expressly claim the limitations set forth in instant claims 21-23, 29, and 35, these limitations are set forth in the reference specification4. Accordingly, the present claims are directed to obvious variants5 of the claimed invention, and a skilled artisan would readily appreciate the limitations set forth in the reference patent, as the they are obvious variations described in the specification of the reference patent (see, e.g., MPEP § 804(II)(B)(1), regarding construing the claim using the reference patent disclosure).
Accordingly, the present claims are not patentably distinct relative to the reference claims.
Response to Arguments
Applicant's arguments filed 03 November 2025 have been fully considered but they are not persuasive. Applicable arguments pertaining to the rejections are addressed below.
In view of the Applicant’s claim amendments, the previous claim rejections under 35 U.S.C. 112 are rendered moot. The previous claim rejections under 35 U.S.C. 103 are maintained, as set forth above. Provisional rejections on the ground of nonstatutory double patenting over Copending Application No. 19/024,886, which was filed 16 January 2025 (after mailing of the previous action on 10 January 2025) are set forth above.
In response to Applicant’s argument that “The combination of cited art would not have motivated one of skill to arrive at the present invention with a reasonable expectation of success. Neither Kaneko nor Vasu discloses or suggest directly coupling antigen to the particle as recited in the present claims and use thereof to reduce an immune response.”: the cited prior art of Vasu and Kaneko provide support for coupling antigen to the biodegradable particle surface, as claimed. The instant claims do not require “direct” coupling of antigen to the particle surface; instant claim 18 merely requires the antigenic peptide to be coupled to the particle, whether it be indirectly or directly. Furthermore, the claims do not contain closed language (e.g., “consisting of”), nor do they include language that explicitly requires the exclusion of an MHC molecule. Accordingly, the prior art teachings of Kaneko and Vasu render obvious the claims, as they disclose coupling an antigen to a particle, and the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)). Furthermore, it is also noted that preferred embodiments do not constitute a teaching away from nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). “A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994).
In response to Applicant’s argument that “the combination of cited art did not provide a reasonable expectation that a nanoparticle comprising antigen alone, outside of the normal antigen-presenting MHC context, would be useful in inducing tolerance”: if Applicant is attempting to allege that the prior art is not enabling or inoperable Applicant is directed to MPEP § 2121(I), which notes that the prior art is presumed fully enabled for all that it discloses, and the burden is on the Applicant to rebut the presumption of operability (see, e.g., MPEP § 2121(I); MPEP § 716.07). No evidence of inoperability commensurate in scope with the requirements of MPEP § 716.07 have been placed on record at this time; critically, arguments of counsel cannot take the place of evidence in the record (see, e.g., In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965), and evidence is required to rebut the presumption of operability.
In response to Applicant’s argument that “The specification demonstrates, however, that nanoparticles with peptide coupled thereto were able to induce tolerance in in vitro (Example 16, 18) and in vivo models (Example 19). This would not have been predicted from the cited art which suggested that antigen presentation in the context of an MHC molecule was necessary to induce tolerance”: if Applicant means to allege the existence of unexpected results commensurate in scope with the requirements of MPEP § 716.02 based upon instant Examples 16, 18, and 19, this is also not persuasive because the requirements of MPEP § 716.02 have not been satisfied. Specifically, MPEP § 716.02(b) and 716.02(e) are not satisfied because Applicant fails to explain and compare the proffered data with the closest prior art. Further, MPEP § 716.02(d) is not satisfied because such proffered evidence is not commensurate in scope with the instant claims with respect to the method as instantly claimed (see, e.g., instant claims 18, 21, 23, 35; see also MPEP § 716.02(d)(I)-(II)); rather, the examples are highly limited to specific particles, antigens, and diseases, and fail to establish that the observed results persist within the full scope and ranges of compositions presently claimed (see, e.g., MPEP § 716.02(d)). Accordingly, for at least these reasons, the proffered data at Examples 16, 18, and 19 is insufficient to establish unexpected results commensurate in scope with the requirements of MPEP § 716.02. Accordingly, zero evidence of any unexpected results commensurate in scope with the requirements of MPEP § 716.02 have been placed on record at this time.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 LEA O'BRIEN whose telephone number is (703)756-4793. The examiner can normally be reached Monday - Thursday 9:00AM - 5PM PT.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory Emch can be reached on (571) 272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LEA S O'BRIEN/Examiner, Art Unit 1646
/MARK HALVORSON/Primary Examiner, Art Unit 1646
1 WO2007087341; cited in the IDS
2 Kaneko et al. “Alloantigen presentation by ethyl carbodiimide-treated dendritic cells induces T cell hyporesponsiveness, and prolongs organ graft survival”, Clin. Immunol., 108(3):190-8 (September 2003); cited in the IDS
3 Tolerance encompasses “reducing an antigen-specific immune response”, as set forth in instant claim 18 (see reference specification, e.g., at para. [0074] to [0075]).
4 See reference specification, e.g., at para. [0144] to [0149]: “In one embodiment, the antigenic peptide… selected from myelin basic protein…”, as well as those set forth in instant claim 21, rendering obvious instant claim 21; para. [0031]: “In some embodiments, said conjugate molecule is ECDI”, renders obvious instant claim 22; para. [0028]: “In some embodiments, said apoptotic signaling molecule is annexin-1, annexin-5, phosphatidyl serine, milk fat globule-EGF-factor 8 (MFG-EB8), Fas-ligand or TNF-alpha”, renders obvious instant claim 23; para. [0167]: “The composition can be administered or delivered to a subject orally, nasally, intravenously, intramuscularly, parenterally, or ocularly”, renders obvious instant claim 29; and para. [0026]: “Apoptotic body surrogates may comprise polyglycolic acid (PGA), polylactic acid (PLA), or poly (lactic-co-glycolic) acid (PLGA)”, renders obvious instant claim 35
5 Per MPEP § 804(II)(B)(1), it is permissible to rely on the Specification for obvious variants (see, e.g., MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”).
Prosecution Insights