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 .
Claim Status
Applicants' response and amendments to the claims, filed 12/22/2025, are acknowledged and entered. No claims were cancelled or newly added.
Claims 1-6, 8-11, 15-18, 22-26, and 29 are pending.
Election/Restrictions
Claims 5-6 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/02/2025.
Information Disclosure Statement
Applicant’s Information Disclosure Statements filed 12/22/2025 has been received and entered into the present application. As reflected by the attached, completed copy of form PTO-1449, the Examiner has considered the cited references to the extent that they comply with the provisions of 37 C.F.R. §1.97, §1.98 and MPEP §609.
Claim Rejections - 35 USC § 112(a) - Written Description
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Claim 3 remains 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.
The claims recite methods of treating an opioid use disorder comprising the administration of a composition comprising an opioid antigen and a TLR7/8 agonist (Claim 1). Claim 3 recites that the TLR7/8 agonist is “an imidazoquinoline compound”.
An “imidazoquinoline” broadly encompasses any chemical compound containing the moiety
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, which can be substituted with any variable chemical moieties at any positions whatsoever.
In contrast, the only imidazoquinoline compounds described by Applicants are compounds of Formula (I),
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wherein R1 is selected from chemical groups containing a phospholipid, lipid, lipidation and/or PEG and R2 is selected from H, alkyl, alkylamino, alkoxy, cycloalkyl, alkylamino groups that are unbranched or branched and optionally terminally substituted with a hydroxyl, amino, thio, hydrazino, hydrazido, azido, acetylenyl, carbonyl, or maleimido group (Specification at p.12-13). Applicants disclose one species of the disclosed genus of imidazoquinoline compounds, the compound of Formula (II) recited in claim 4:
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.
Vas-Cath Inc. V. Mahurkar, 19 USPQ2d 1111, states that Applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention, for purposes of the written description inquiry, is whatever is now claimed (see page 1117). The court in Eli Lilly held that an adequate written description of a claimed genus requires more than a generic statement of an invention's boundaries. Regents of the University of California v. Eli Lilly & Co., 119 F3d at 1568. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 94 USPQ2d 1161 (Fed. Cir. 2010) states that “…a generic claim may define the boundaries of a vast genus of chemical compounds…the question may still remain whether the specification, including the original claim language, demonstrates that the applicant invented species sufficient to support a claim to a genus”. See page 1171. A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or structural features common to the members of the genus, which features constitute a substantial portion of the genus, so that one of skill in the art can “visualize or recognize” the members of the genus (Emphasis added). Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997).
Here, Applicants fail on all counts to describe the claimed “an imidazoquinoline compound” as recited in claim 3 that are purported to be agonists of TLR7/8. Applicants merely disclose and describe a single species of each claimed genus. A person of ordinary skill in the art would not be able to predict the operability of any given “imidazoquinoline compound” to agonize TLR7/8, let alone act as an adjuvant for an opioid antigen as presently claimed.
As the courts have repeatedly stated, the 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.” Rochester, 358 F.3d at 920 (quoting Reiffin v. Microsoft Corp., 214 F.3d 1342, 1345 [54 USPQ2d 1915] (Fed. Cir. 2000)).
Here, Applicants desire patent protection for methods that comprise administering any TLR 7/8 agonist “imidazoquinoline compound” as opioid antigen adjuvants. To support such broad protection and right to exclude, Applicants describe the claimed genus only by providing a partial structure having numerous broadly defined variable substituents attached thereto and a single species of the genus. However, the disclosure of this partial structure and species merely provides a generic statement of an invention's boundaries but fails to demonstrate that the applicant invented species sufficient to support claims to the genus “an imidazoquinoline compound” that is an agonist of both TLR7 and TLR8.
At best, Applicant’s Specification directs one to make imidazoquinoline compounds that fall within the extremely large scope of Applicant’s claims and then figure out, through trial-and-error testing, which of these compounds are capable of agonizing TLR7/8 and also capable as acting as vaccine adjuvants. This activity would require “excessive trial and error experimentation” (FF 14). See In re ʼ318 Patent Infringement Litigation, 583 F.3d 1317, 1327 (Fed. Cir. 2009) (“[A]t the end of the day, the specification, even read in light of the knowledge of those skilled in the art, does no more than state a hypothesis and propose testing to determine the accuracy of that hypothesis. That is not sufficient.”).
Accordingly, the specification does not provide adequate written description of the claimed genus “an imidazoquinoline compound”, which is a generic genus of compounds purported to be TLR7/8 agonists and to act as vaccine adjuvants. One of skill in the art would not recognize from the disclosure that the applicant was in possession of the genus. The specification does not clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed (see Vas-Cath at page 1116).
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112 is severable from its enablement provision (see page 1115).
Response to Arguments
Applicants traverse arguing that as of the effective filing date of the application numerous imidazoquinoline compounds “of Formula I” were known in the art to be TLR7/8 agonists. Citing Smith et al., Applicants argue Smith et al. discloses three imidazoquinoline compounds “(e.g., imidazoquinoline compounds of Formula I)” that demonstrate TLR7/8 agonist activity. Applicants further argue that extensive structure-activity relationship studies have established clear relationships between structural modifications of imidazoquinoline compounds “(e.g., imidazoquinoline compounds of Formula I)” and their biological activity.
The Examiner does not disagree that imidazoquinoline compounds of Formula I were known in the art to have TLR7/8 agonist activity. The claims, however, do not recite imidazoquinoline compounds of Formula I but rather are generic to any “imidazoquinoline compound”. Applicant’s citation to a relatively small number of known imidazoquinoline compounds having TLR7/8 agonist activity does not establish any and all compounds having an imidazoquinoline core, regardless of other chemical substitutions thereon, would be reasonably expected to also have TLR7/8 agonist activity.
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 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.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1-4, 8-9, 11, 15-18, 22-26, and 29 are rejected under 35 U.S.C. 103(a) as being unpatentable over WO 2020/018596 A1 (Published January 23, 2020; Filed July 16, 2019)1 in view of VASILAKOS ET AL. (Expert Rev. Vaccines, 2013, 12(7), p.809-819) and DOWLING (Immunohorizons, July 3, 2018, 2(6), p.185-197).
The claims are drawn to composition and methods comprising opioid antigen and a toll-like receptor 7 and 8 (TLR7/8) agonist. Claims 1 and 23 are representative and are reproduced below.
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WO ‘596 teaches methods of treating or preventing opioid use disorder, methods of treating opioid overdose, and methods of generating and/or isolating antibodies selective for opioids (Abstract). The method comprises, inter alia, treating opioid use disorder and/or preventing opioid use disorder and/or treating an opioid overdose in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound of fentanyl haptens of Formula (D1), (D2), (D3), (D4) or (D5) [claimed “opioid antigen”], wherein the opioid is fentanyl ([0172]). Compositions are described that are intended to be administered to a subject for the purpose of generating antibodies and/or treating or preventing opioid use disorder comprising the compound of Formula (A1) or (A2) and an adjuvant ([0157]-[0158]). Suitable adjuvants are disclosed to include, inter alia, aluminum salts and toll like receptor agonists ([0087]). In some aspects, a combination of a toll-like receptor agonist and an aluminum salt is disclosed ([0087]; [0164]). Aluminum salts include potassium aluminum sulfate, i.e., “alum”, as recited in claims 11 and 25 ([0088]; [0164]). The toll-like receptor agonist is a toll-like receptor 2 agonist, toll-like receptor 3 agonist, toll-like receptor 4 agonist, toll-like receptor 5 agonist, toll-like receptor 7 agonist, toll-like receptor 8 agonist, toll-like receptor 9 agonist ([0090]; [0164]). Embodiment P1 describes a fentanyl hapten of formula 1:
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([0179]). Embodiment 38 describes a vaccine comprising the compound of, inter alia, Embodiment P1, and a pharmaceutically acceptable adjuvant ([0225]). Embodiment 39 describes the vaccine of Embodiment 38, wherein the adjuvant is an aluminum salt, and Embodiment 40 describes the vaccine of Embodiment 39, wherein the aluminum salt is, inter alia, potassium aluminum sulfate [alum] ([0226])-[0227]). Embodiments 41 and 42 describe the vaccine of Embodiments 38-40 wherein the adjuvant comprises a toll-like receptor agonist that is a toll-like receptor 2 agonist, toll-like receptor 3 agonist, toll-like receptor 4 agonist, toll-like receptor 5 agonist, toll-like receptor 7 agonist, toll-like receptor 8 agonist, toll-like receptor 9 agonist, or a combination of two or more thereof ([0228]-[0229]).
WO ‘596 thus teaches compositions and methods for treating an opioid use disorder in a subject comprising administering a composition comprising an opioid antigen and adjuvants such as toll-like receptor agonists and alum. WO ‘596 differs from the instant claims in so far as it does not expressly disclose a TLR7/8 agonist, e.g., a compound of Formula II [resiquimod], as the TLR agonist adjuvant.
VASILAKOS ET AL. teach that small molecule TLR7/8 agonist have demonstrated potential as vaccine adjuvants, since they directly activate APCs and can enhance both humoral and cellular immune responses (Abstract). They teach the vast majority of vaccine studies performed thus far have been performed with synthetic small molecule imidazoquinolines, such as imiquimod and resiquimod [claimed imidazoquinoline compound of Formula II as recited in claim 4] (Abstract). Regarding alum as a vaccine adjuvant as taught in WO ‘596 and recited in claims 11 and 25, they teach that alum is the most widely used adjuvant in the world today (paragraph bridging p.809-810). They teach that they are purposefully adding defined TLR agonists to vaccine formulations with the intent of improving the effectiveness of vaccines and that the approval of the TLR4 agonist, monophosphoryl lipid A, as a vaccine adjuvant lends credibility to using TLR agonists as vaccine adjuvants (paragraph bridging p.810-811). Regarding combining TLR agonist as vaccine adjuvants, they teach that numerous studies have demonstrated that combinations of TLR agonists, e.g., TLR4 and TLR7/8 (resiquimod) agonists, can be combined to improve DC maturation and B- and T-cell activation (p.814, left column).
DOWLING teaches small molecule TLR7/8 agonists have demonstrated great potential as vaccine adjuvants and the most promising innovations in formulation and use of delivery systems for TLR7/8 agonists include 1) lipidation approaches, 2) encapsulating nanoparticles, 3) adsorption to alum adjuvants, 4) conjugation to polymers or protein Ags, and 5) additive/synergistic admixture combinations with other adjuvants such as TLR4 adjuvants (Figure 2). Regarding incorporating the TLR7/8 agonist into a liposome as recited in claim 8, they teach the TLR7 agonist imiquimod has been encapsulated in an anionic liposome with the TLR4 agonist GLA for use as an adjuvant in a vaccine for malaria (Table II). Regarding combining TLR7/8 agonist with other adjuvants such as a TLR4 agonist as encompassed by claims 9 and 24, they teach that perhaps the most studies combination formulation strategy involves simple coadministration of TLR7/8 adjuvants with TLR4 agonists, simply admixes or in liposomal and emulsion formulations (p.192, left column; Table V).
It would have been obvious before the effective filing date of the claimed invention to administer a composition comprising an opioid antigen, e.g., a fentanyl hapten, and a TLR7/8 adjuvant to treat opioid use disorder in a subject as expressly suggested by the combined teachings of the cited prior art. On exemplary rationale for the Examiner’s finding of obviousness is the combining of prior art elements according to known methods to yield predictable results. In this regard, the prior art teaches each element claimed: 1) the administration of compositions comprising opioid antigens such as fentanyl haptens and vaccine adjuvants such as alum and/or TLR agonists (WO ‘596) and 2) the administration of TLR7/8 agonists as vaccine adjuvants (Vasilakos et al. and Dowling). The only difference between the claims and the teachings of WO ‘596 is the use of a TLR7/8 agonist as the adjuvant. A person of ordinary skill in the art could have combined the opioid antigens taught in WO ‘596 with the known TLR7/8 agonist vaccine adjuvant of Formula II (resiquimod) as taught in both Vasilakos et al. and Dowling by the known methods taught in WO ‘596, Vasilakos et al., and Dowling, with the expectation that the TLR7/8 agonist would predictably function as a vaccine adjuvant for the opioid antigens taught in WO ‘596. In this regard, WO ‘596 expressly teaches that any TLR agonist or combination of TLR agonists can be used as adjuvants in the compositions and methods taught therein. Accordingly, formulating a composition comprising an opioid antigen and a TLR7/8 agonist as an adjuvant and administering such a composition to a subject in need of treating an opioid use disorder as encompassed by claims 1-4, 15-18, 23, 26, and 29 would have been prima facie obvious over the combined teachings of WO ‘596, Vasilakos et al., and Dowling.
Claim 8 requires the TLR7/8 agonist is incorporated into a liposome and claims 9 and 24 require the further administration of a TLR4 agonist, which are suggested by the teachings of Dowling who teach perhaps the most studies combination formulation strategy involves simple coadministration of TLR7/8 adjuvants with TLR4 agonists, simply admixes or in liposomal and emulsion formulations (p.192, left column; Table V). Vasilakos et al. also teach that numerous studies have demonstrated that combinations of TLR agonists, e.g., TLR4 and TLR7/8 (resiquimod) agonists, can be combined to improve DC maturation and B- and T-cell activation (p.814, left column). Accordingly, coadministering a TLR7/8 agonist and a TLR4 agonist as vaccine adjuvants in the methods of WO ‘596 would have been prima facie obvious in view of the combined teachings of WO ‘596, Vasilakos et al., and Dowling.
Claims 11 and 25 require the composition further comprises alum, which is expressly suggested by the teachings of WO ‘596, which teaches a combination of a toll-like receptor agonist and an aluminum salt ([0087]; [0164]), wherein the aluminum salts include potassium aluminum sulfate, i.e., “alum”, ([0088]; [0164]), and Vasilakos et al. who teach alum is the most widely used adjuvant in the world today (paragraph bridging p.809-810). Accordingly, administering both a TLR7/8 agonist and alum as vaccine adjuvants in the methods of WO ‘596 would have been prima facie obvious in view of the combined teachings of WO ‘596, Vasilakos et al., and Dowling.
For the above reasons, claims 1-4, 8-9, 11, 15-18, 22-26, and 29 are properly rejected as being prima facie obvious over WO ‘596 in view of Vasilakos et al. and Dowling.
Response to Arguments
Applicants traverse arguing that the pending claims are non-obvious because the combination of references would not have led the skilled person to expect that a TLR7/8 agonist could be used in a method of treating an opioid use disorder. Specifically, Applicants appear to be asserting that the cited references do not provide any guidance that would have led one of ordinary skill in the art to expect that a TLR7/8 agonist would be “superior” to other agonists when treating opioid use disorder.2 For example, Applicants argue that none of Vasilakos or Dowling provide a skilled person with a reason to expect that a TLR7/8 would have superior properties to other agonists when treating an opioid use disorder.3 Applicants argue that they surprisingly found that TLR7/8 agonist induce a better immune response in youth as compared to numerous other agonists, citing the instant application at [0115] (Example 1).
In response, the Examiner first submits that the combined teachings of the cited prior art need not disclose or suggest that a TLR7/8 agonist would necessarily be “superior” to other agonists when treating opioid use disorder. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., superiority of TLR7/8 agonists relative to other agonists) are not recited in the rejected claim(s). 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). All that is required to be taught or reasonably suggested by the combined teachings of the cited prior art is administering an effective amount of a composition comprising an opioid antigen and a TLR7/8 agonist to a subject in need of treating an opioid use disorder (Claim 1).
Turning now to Applicant’s argument of unexpected results, i.e., that TLR7/8 agonists induce a better immune response in youth as compared to numerous other agonists, Example 1 of the disclosure only establishes that immune responses in youth with OUD may be distinct from their control healthy counterparts. In vivo working examples in mice (Example 2) and rats (Example 3) are limited to administration of fentanyl antigens and a single TLR7/8 agonist (compound of Formula IV). Accordingly, even if it could be argued that Applicants have demonstrated unexpected results, such results are not commensurate in scope with the present claims, which encompass administering any “opioid antigen” and any TLR7/8 agonist. There is no factual evidence of record that the results demonstrated by Applicants for administration of fentanyl antigens and the TLR7/8 agonist of Formula IV would predictably extend to administration of other opioid antigens and/or other TLR7/8 agonists.
Allowable Subject Matter
Claim 10 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claims 1-4, 8-9, 11, 15-18, 22-26, and 29 are rejected.
Claim 10 is objected to.
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.
Applicant is requested to specifically point out the support for any amendments made to the disclosure in response to this Office action, including the claims (M.P.E.P. §§ 714.02 and 2163.06). In doing so, applicant is requested to refer to pages and line (or paragraph) numbers (if available) in the as-filed specification, not the published application. Due to the procedure outlined in M.P.E.P. § 2163.06 for interpreting claims, other art may be applicable under 35 U.S.C. § 102 or 35 U.S.C. § 103(a) once the aforementioned issue(s) is/are addressed.
Applicant is reminded that MPEP §2001.06(b) clearly states that “[t]he individuals covered by 37 C.F.R. 1.56 have a duty to bring to the attention of the examiner, or other Office official involved with the examination of a particular application, information within their knowledge as to other copending United States applications which are "material to patentability" of the application in question." See Armour & Co. v. Swift & Co., 466 F.2d 767, 779, 175 USPQ 70, 79 (7th Cir. 1972). MPEP §2001.06(b) clearly indicates that “if a particular inventor has different applications pending in which similar subject matter but patentably indistinct claims are present that fact must be disclosed to the examiner of each of the involved applications.” See Dayco Prod. Inc. v. Total Containment, Inc., 329 F.3d 1358, 1365-69, 66 USPQ2d 1801, 1806-08 (Fed. Cir. 2003).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES D ANDERSON whose telephone number is (571)272-9038. The examiner can normally be reached on Monday-Friday, 7:30 am - 4:00 pm PST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Lundgren can be reached on 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/James D. Anderson/Primary Examiner, Art Unit 1629
UNITED STATES PATENT AND TRADEMARK OFFICE
500 Dulany Street
Alexandria, VA 22314-5774
Tel. No.: (571) 272-9038
1 WO ‘596 qualifies as prior art under 35 U.S.C. 102(a)(2) being effectively filed (July 16, 2019) before the filing date of the claimed invention (October 17, 2019).
2 Arguments at paragraph bridging p.7-8.
3 Arguments at p.8, 1st full paragraph.