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 .
Status of Application, Amendments and/or Claims
The amendment and Applicant’s arguments, filed 16 April 2026, have been entered in full. Claims 1, 3-5, 7 and 8 are withdrawn from consideration as being drawn to a non-elected invention. Claims 2, 6, 10, 12 and 13 are canceled. Claims 9 and 11 are amended. New claims 14-17 are added. Claims 9, 11, 14-17 are under examination.
Withdrawn Objections And/Or Rejections
The objections to claims 9-11, as set forth at pages 3-4 of the previous Office Action (09 February 2026), are withdrawn in view of the amendment (16 April 2026).
The rejection to claim 9 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, scope of enablement, as set forth at pages 4-7 of the previous Office Action (09 February 2026), is withdrawn in view of the amendment (16 April 2026).
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 9, 11 (and new claims 14-17) remain rejected under 35 U.S.C. 103 as being unpatentable over Janda et al. (US 2022/0081400; published March 17, 2022, priority date July 16, 2018) in view of Valli et al. (LTA1 is a safe, intranasal enterotoxin-based adjuvant that improves vaccine protection against influenza in young, old and B-cell-depleted (µMT) mice. Scientific Reports Volume 9:15128, 2019).
The basis for this rejection is set forth at pages 7-10 of the previous Office Action (09 February 2026).
APPLICANT’S ARGUMENTS: Applicant discusses the pending rejection set forth in the previous Office action. Applicant submits that there are no teachings in Janda and Valli that would suggest to a person of skill in the art that the claimed methods could produce the extremely high levels of efficacy demonstrated in the specification that are attributable to the combination of the claimed protein-hapten conjugate and the claimed adjuvants. Applicant submits that the inclusion of adjuvants dmLT and LTA1 results in notable improvements and enhanced effectiveness relative to the use of the protein-hapten conjugate alone as well as compared to the use of the protein-hapten conjugate with other adjuvants. Applicant argues that as discussed in the specification at paragraphs [0051]-[0053] and shown in FIG. 2-4, administration of the claimed protein-hapten conjugate with dmLT or LTA1 produced greater amounts of serum anti-fentanyl antibodies and antibody secreting cells in mice compared to administration of the protein-hapten conjugate alone, or the protein-hapten conjugate with the adjuvant alum (i.e. aluminum hydroxide, aluminum hydroxyphosphate sulfate).
Applicant argues that paragraph [0054] and FIG. 5 demonstrate that the claimed protein-hapten conjugate admixed with either dmLT or LTA1 produced an elevation in anti-fentanyl antibodies relative to the same administrations of the protein-hapten conjugate alone. Applicant argues that the application also includes data discussed in paragraph [0055] of the specification and shown in FIG. 6 demonstrating that the analgesic effects of fentanyl were significantly attenuated in mice vaccinated with the claimed protein-hapten conjugate and dmLT, compared to mice vaccinated with the protein-hapten conjugate alone.
Applicant maintains that there are significant unexpected benefits associated with the combination of the claimed protein-hapten conjugate and the claimed adjuvants dmLT and LTA1. Applicant argues that the Office Action cites to Valli as suggesting that dmLT and LTA1 are safe and effective adjuvants in vaccines, such as vaccines for the flu or other infectious diseases. Applicant submits that nothing in Valli suggests that the use of dmLT or LTA1 would produce an improvement in efficacy in the field of opioid vaccines. Applicant argues that opioid vaccines stimulate the production of antibodies that prevent opioids from entering the central nervous system, while flu vaccines stimulate the immune system to recognize the virus and prevent it from replicating. Applicant maintains that the difficulties understood in the art surrounding the use of opioid vaccines are the inability to obtain sufficient antibody levels to respond to the drug and prevent CNS entry. Applicant submits that the claimed methods - using the adjuvants dmLT and LTA1 - produce higher amounts of anti- fentanyl antibodies than the protein-hapten conjugate alone. Applicant argues that the use of the claimed adjuvants also produces greater amounts of anti-fentanyl antibodies than the use of other adjuvants such as alum. Applicant maintains that these results are unexpected in the field of opioid vaccines and would have been unforeseeable to those of ordinary skill in the art in view of Janda and Valli.
Applicant’s arguments have been fully considered but are not found persuasive for the following reasons:
1. As was stated in the previous Office Action, Janda et al. teach an opioid vaccine comprising the recited protein-hapten conjugate and methods of administering said vaccine to treat opioid use disorder, inhibit the effects of opioids and prevent opioid overdoses. Janda et al. teach that the vaccine can be administered intramuscularly, intranasally or sublingually. Janda et al. teach adjuvants, but not adjuvants LTA1 or dmLT.
2. Regarding Applicant’s argument that the inclusion of adjuvants dmLT and LTA1 results in notable improvements and enhanced effectiveness relative to the use of the protein-hapten conjugate alone and that the results are unexpected:
The Examiner notes that an adjuvant, by definition, is a substance that enhances, modifies, or assists the effectiveness of a primary ingredient. Adjuvants are known to be added to vaccines to boost the body’s immune response and enhance the effectiveness of the vaccine. Therefore, this result is not unexpected.
3. Regarding Applicant’s argument that the inclusion of adjuvants dmLT and LTA1 results in notable improvements and enhanced effectiveness relative to the use of the protein-hapten conjugate with other adjuvants and that the results are unexpected:
Valli et al. teach that enterotoxin-based adjuvants, such as heat-labile toxin (LT) are powerful manipulator of mucosal immunity, but past clinical trials identified unacceptable neurological toxicity when LT adjuvant was added to intranasal vaccines. Valli et al. teach the use of adjuvant LTA1, wherein the B-subunit in LT was removed. Valli et al. teach no neurological toxicity but the same efficacy. Valli et al. teach adjuvant dmLT, has exhibited success in Phase 1 and Phase 2 clinical trials. Thus, the argument that adjuvants dmLT and LTA1 worked better than adjuvants such as aluminum hydroxide and aluminum hydroxyphosphate sulfate, is not an unexpected result because Valli et al. teach that these adjuvants (i.e. enterotoxin-based adjuvants) are very powerful.
4. Regarding Applicant’s arguments that nothing in Valli suggests that the use of dmLT or LTA1 would produce an improvement in efficacy in the field of opioid vaccines, that opioid vaccines stimulate the production of antibodies that prevent opioids from entering the central nervous system, while flu vaccines stimulate the immune system to recognize the virus and prevent it from replicating and that difficulties understood in the art surrounding the use of opioid vaccines are the inability to obtain sufficient antibody levels to respond to the drug and prevent CNS entry:
The Examiner disagrees with Applicant’s assessment.
The body will stimulate antibodies when vaccinated with an opioid vaccine and will stimulate antibodies when vaccinated with a flu vaccine. In the case of an opioid vaccine, the body will produce antibodies against the opioid. In the case of the flu vaccine, the body will produce antibodies against a particular strain of influenza.
The purpose of the added adjuvant is to enhances the response/efficacy (e.g. stimulating the production of antibodies). Valli et al. teach that dmLT and LTA1 are powerful adjuvants.
Valli et al. teach that intranasal (IN) vaccination is an attractive delivery route due to the ease of administration, lack of injection-related infections, low antigen doses and the induction of robust systemic and mucosal immunity. Valli et al. teach the use of the adjuvant LTA1 as an intranasal adjuvant in vaccine development.
Contrary to the presented arguments, adjuvants dmLT and LTA1 are not just applicable to flu vaccines. Based on the teachings, it would be obvious to use LT adjuvants such as dmLT or LTA1 because they are strong adjuvants and adjuvant LTA1 can be administered intranasally.
The scientific reasoning and evidence indicates that the rejection should be maintained.
NEW REJECTION/OBJECTION
Claim Rejections-35 USC § 112(a) or 35 U.S.C. 112 (pre-AIA ), First paragraph, Scope of Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 11, 16 and 17 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
“A method of inhibiting effects of opioids in a subject or preventing effects of opioids in a subject, wherein said prevented effects are analgesic effects and lethality..”
does not reasonably provide enablement for:
“A method of preventing effects of opioids in a subject..”
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
APPLICANT’S ARGUMENTS: Applicant argues that to advance prosecution, Applicant has amended Claim 1 to remove "preventing" as it relates to opioid use disorder. Applicant has also amended Claim 1 to recite "preventing opioid overdose" in a subject. Applicant submits that the data and examples in the specification support the use of the pharmaceutical composition to prevent opioid overdose and respectfully requests that this rejection be withdrawn.
Applicant’s arguments have been fully considered and are found partly persuasive for the following reasons:
1. The Examiner believes Applicant is intending to refer to instant claim 9 and claim 11.
Claim 9 has been amended to delete the limitation “preventing”. Amended claim 9 now recites “A method of treating opioid use disorder or preventing opioid overdose in a subject..”.
The Examiner notes that the rejection to claim 9 is withdrawn in view of the new amendment to claim 9. Please see above in the section “Withdrawn Objections And/Or Rejections”.
2. The Examiner notes that instant claim 11 has been amended to recite “preventing”; “preventing effects of opioids in a subject”. New claims 16 and 17 depend from amended claim 11.
The Rice et al. reference was submitted in the previous Office Action. Rice et al. teach that opioid use can cause psychosocial distress, illicit drug use, alcohol use, HIV risk behaviors, changes in mental health symptoms (depression, anxiety and suicidality), measures of craving and changes in patients' quality of life.
The Examiner maintains that opioids can cause many different effects in subjects, included those discussed in the Rice et al. reference. The limitation “preventing” is not a relative term, it is total.
While the Examples demonstrate preventing effects of opioids in a subject, wherein said prevented effects are analgesic effects and lethality, the specification is not enabled for the full breadth of “preventing effects of opioids” in a subject. It could not be predicted that administering the recited vaccine would completely and fully stop the varied physical and mental issues caused by opioids from ever occurring in a subject.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REGINA M DEBERRY whose telephone number is (571)272-0882. The examiner can normally be reached M-F 9:00-6:30 pm (alt Fri).
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/R.M.D/Examiner, Art Unit 1647 6/16/2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647
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