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 . 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.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 05/11/2026 has been entered.
Priority
The instant application is a 371 of PCT/EP2020/074046 filed on 08/28/2020 and claims foreign
priority to European application no. EP19193982.6 filed on 08/28/2019. The certified copy of the foreign
priority application filed on 02/18/2022 in the instant application is acknowledged.
Status of the Claims
The claim amendments and remarks filed on 05/11/2026 is acknowledged. Claims 1, 8, 10, 14, 18, and 21 are amended. Claims 2, 4-7, and 15-16 are cancelled.
Accordingly, claims 1, 3, 8-14, and 17-21 are pending and being examined on the merits herein.
Withdrawn Objections/Rejections
The objection to the specification is withdrawn because the recited formula on page 5 and 8 shows the phosphorous groups at the +5 oxidation as previously amended in the claims.
The objection to claims 1 and 21 are withdrawn because the recited formula (I) in claim 1 has sufficient resolution and claim 21 was amended to refer to the structure recited in claim 1.
The 35 USC 112(b) rejection over claim 8 is withdrawn because it is now clear that each R3 group is OH and each X group is an oxygen atom.
The 35 USC 102 rejection over claims 1-2, 7-8, 10-14, and 19-21 over Borriello is withdrawn because the cGAMP compound disclosed in Borriello does not anticipate the recited formula (I) structure in instant claim 1.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 recites “R2 is independently from one another NH2, O, H, or a hydrogen”.
It is suggested to remove the term “hydrogen” as the prior recitation of “H” makes the “hydrogen” redundant.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1, 3, 8-14, and 17, and 19-21 are rejected under 35 U.S.C. 103 as being unpatentable over Borriello et al. (Frontiers in Immunology, 2017 in PTO-892 dated 11/17/2025) and as evidenced by Sureka et al. (Cell, 2014 in PTO-892).
Borriello teaches the use of STING ligands and their formulations for enhancement of early life immunization (see second paragraph right column page 2).
Borriello teaches that vaccines often demonstrate reduced efficacy in newborns and young infants compared to adults due to age-specific immunity (see Abstract). Borriello teaches that newborn innate immune cells exhibit distinct activation profiles in response to pattern recognition receptor (PRR) agonists and only certain PRR agonists or their combinations are able to induce an adult-like response (see left column first paragraph page 2). Borriello teaches that neonatal CD4+ T cells produce lower amounts of IFN-gamma and are skewed toward Th2, Th17, and Treg polarization (see left column first paragraph page 2). Borriello further teaches that adjuvants exhibit age-specific patterns of Th-polarization such that adjuvantation systems that boost adult immune responses do not necessarily lead to enhanced vaccine efficacy in newborns or young infants (see left column first paragraph page 2). Therefore, Borriello teaches that identification of vaccine adjuvants capable of activating neonatal and infant immune responses may inform development of adjuvanted vaccine formulations that enhance early life immunization (see left column first paragraph page 2).
Borriello teaches that dendritic cells (DCs) play a pivotal role in activating T cells and instructing the adaptive immune response (see second paragraph left column page 2). Borriello teaches these cells express a high diversity of PRRs, whose activation leads to DC migration to lymph nodes and enhancement of immune-stimulatory functions (see second paragraph left column page 2). Borriello teaches that a systems vaccinology analysis of young infants vaccinated with trivalent inactivated influenza vaccine with or without the oil-in-water adjuvant MF59 demonstrated that innate immune gene signatures (e.g., antiviral and DC genes) 1-day post-immunization correlated with vaccine efficacy, highlighting the importance of robust innate immune activation in early life immunization (see second paragraph left column page 2). Borriello teaches that agonists of the intracellular receptors TLR7/8, that recognize viral single-stranded RNAs, potently activate Th1-polarizing responses, including expression of interferons (IFNs), production of IL-12p70 and upregulation of co-stimulatory molecules in newborn DCs in vitro and enhance vaccine efficacy in newborn non-human primates in vivo (see second paragraph left column page 2). Moreover, Borriello teaches that adjuvantation with the TLR9 agonist CpG increases CG Tfh and B cell responses in newborn mice (see second paragraph left column page 2).
Borriello teaches that among intra-cellular PRRs, the stimulator of interferon genes (STING) is an amenable target for adjuvant discovery and development (see second paragraph left column page 2). Borriello teaches that it binds cyclic dinucleotides (CDNs) derived from bacteria (i.e., c-di-AMP, c-di-GMP, and 3′3′-cGAMP) or synthesized in mammalian cells by cGAMP synthase in response to double-stranded DNA in the cytoplasm (i.e., 2′3′-cGAMP) (see second paragraph left column page 2 through first paragraph right column page 2). Here, as evidenced by the instant specification on page 6 line 5, the c-di-AMP disclosed in Borriello is also to referred to as CDA and meets the recited formula (I) structure in instant claim 1. Furthermore, as evidenced by Sureka et al. (Figure S1 page S5), c-di-AMP has the following structure shown below:
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Here, c-di-AMP meets the formula (I) when each X is O, Y and Y’ are O, Z and Z’ are O, both R1 are hydrogen, both R2 is NH2, R3s are either absent due to a covalent bond between the Z or Z’ and C atom as well as OH, both R4 are hydrogen, and the purine residues are adenine.
Borriello teaches that upon activation, STING induces the TBK-1-mediated phosphorylation of IRF3, which in turn modulates the expression of type I IFNs, IFN stimulated genes, and also promotes DC maturation and type 1 (i.e., IFNγ-driven) immunity (see first paragraph right column page 2). Accordingly, Borriello teaches that STING agonists have demonstrated promising adjuvanticity in adult experimental models of parenteral and mucosal immunization as well as cancer immunotherapy (first paragraph right column page 2).
Borriello identified STING agonist 2’3’-cGAMP (cGAMP) as an adjuvant candidate for early life immunization from a screening test of PRR agonists (see Abstract and Figure 1 on page 6). Borriello teaches that cGAMP induces a comparable expression of surface maturation markers in newborn and adult bone marrow derived dendritic cells (BMDCs) (see Abstract and first paragraph left column on page 5).
Borriello utilized the trivalent recombinant hemagglutinin (rHA) influenza vaccine, Flubock, as a model antigen to investigate the role of cGAMP in adult and early life immunization (see Abstract). Borriello demonstrates that Flublok immunization formulated with both cGAMP and alum (Alhydrogel) enhanced rHA-specific IgG2a/c titers ~400 fold in newborn mice, which is an antibody subclass associated with the development of IFN gamma-driven type 1 immunity in vivo and endowed with higher effector functions, by 42 days of life (see Abstract and Figure 2 on page 7). Borriello teaches that both nenonate and adult mice were immunized by intramuscular injection to the right posterior thigh (see last paragraph left column on page 3). Borriello concludes that cGAMP when formulated with alum may represent an effective adjuvantation system to foster humoral and cellular aspects of type 1 immunity for early life immunization (see Abstract).
Even though Borriello does not demonstrate the use of CDA as an adjuvant in their study, it would have been prima facie obvious to substitute cGAMP with c-di-AMP as disclosed in Borriello to arrive at the claimed invention.
One of ordinary skill in the art would have substituted one known element (cGAMP) for another (c-di-AMP) to obtain predictable results and would have a reasonable expectation of success in doing so because Borriello provides guidance that cyclic dinucleotides including c-di-AMP and cGAMP are STING agonists that induce immune responses and further demonstrates the use of a STING agonist cGAMP in combination with alum as adjuvants for enhanced early life immunization, which suggests that a combination of alternative cyclic dinucleotide STING agonists such as c-di-AMP and alum would also result in the same enhanced adjuvant effect for early life immunization.
In regards to instant claim 3, it would have also been prima facie obvious before the effective filing date of the claimed to modify the method of Borriello for mucosal administration as suggested in Borriello to arrive at the claimed invention.
One of ordinary skill in the art would have combined prior art elements according to known methods to yield predictable results and would have a reasonable expectation of success in doing so because Borriello provides guidance that STING agonists have demonstrated promising adjuvanticity in adult experimental models of parenteral and mucosal immunization.
In regards to instant claim 21, the recited kit merely serves as a support and does not have a functional relationship to the recited formulation. Therefore, the recited kit is owed no patentable weight, and the recited formulation is rendered obvious as discussed above. MPEP 2111.05 states “"[O]nce it is determined that the limitation is directed to printed matter, [the examiner] must then determine if the matter is functionally or structurally related to the associated physical substrate, and only if the answer is ‘no’ is the printed matter owed no patentable weight." and MPEP 2111.05 I. B states “Where a product merely serves as a support for printed matter, no functional relationship exists.”
Claim(s) 3 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Borriello et al. (Frontiers in Immunology, 2017 in PTO-892 dated 11/17/2025), as applied to claim 1 above, and further in view of Madhun et al. (Vaccine, 2011 in PTO-892 dated 11/17/2025).
The teachings of Borriello are as described above and teach the method of claim 1 as discussed above.
The difference between Borriello and the claimed invention is that Borriello does not teach wherein the compound is administered as a mucosal adjuvant.
Madhun teaches intranasal c-di-GMP-adjuvanted plant-derived H5 influenza vaccine that induces multifunctional Th1 CD4+ cells and strong mucosal and systemic antibody responses in mice (see Abstract). Madhun demonstrates in Fig. 2 on page 4975 that intranasal administration of c-di-GMP-adjuvanted vaccine enhanced immune response whereas intramuscular administration did not. Madhun teaches that the intranasal vaccine also elicited a balanced Th1/Th2 profile (see Abstract), and further teaches that a needle-free intranasal influenza vaccine is an attractive approach, which is easy to administer, likely to have high public compliance, and optimal for mass vaccination (see right column page 4973).
It would have been prima facie obvious before the effective filing date of the claimed invention to modify the method of Borriello by administering their vaccine formulation intranasally as disclosed in Madhun to arrive at the claimed invention.
One of ordinary skill in art would have been motivated to make this modification because Madhun demonstrates that a similar c-di-GMP adjuvanted influenza vaccine that was administered via intranasal had several advantages including enhanced immune response and balanced Th1/Th2 profiles, and provides further guidance that a needle-free intranasal influenza vaccine is an attractive approach, which is easy to administer, likely to have high public compliance, and optimal for mass vaccination.
One of ordinary skill in the art would have a reasonable expectation of success because both Borriello and Madhun teach the use of cyclic dinucleotide adjuvanted influenza vaccines.
Response to Arguments
Applicant’s arguments filed on 05/11/2026 have been fully considered but were not persuasive.
Applicant states that while Borriello discloses that both cGAMP and CDA are distinct agonists, the prior art provides no reason that CDA would be a superior adjuvant in the unique and challenging context of neonatal immunization. Applicant states that the neonatal immune system is unpredictable and that results from adult models often fail. Furthermore, Applicant states that Borriello teaches the combination of cGAMP and Alum would allow to achieve vaccination, whereas the instant invention recognizes that CDA alone is sufficient to work as an adjuvant. Applicant points to FIG. 1b and 1c in which CDA achieves unexpected superior results compared to the gold standard adjuvant R848 in promoting a significantly higher frequency and superior quality for neonatal vaccination. Applicant states that this surprising effect is also demonstrated in FIG. 3 and therefore these unexpected results is non-obvious over the prior art such as Borriello, which teaches the combination of cGAMP and alum to increase titers in newborn mice.
First, in regards to Applicant’s statement that the neonatal immune system is unpredictable and that results from adult models often fail, MPEP 2143.02 I states that “Conclusive proof of efficacy is not required to show a reasonable expectation of success … "To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’" … "This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness." … reasoning that "the expectation of success need only be reasonable, not absolute".
Here, even though adult vaccination models may not be predictable for neonatal vaccinations, Borriello does demonstrate that Flublok immunization formulated with a combination of a cyclic dinucleotide STING agonist (cGAMP) and alum (Alhydrogel) enhanced rHA-specific IgG2a/c titers ~400 fold in newborn mice. Furthermore, Borriello discloses that cyclic dinucleotides including c-di-AMP (CDA) and cGAMP are all STING agonists that induce immune responses. Therefore, while Borriello does not demonstrate the use of CDA for neonatal vaccination, an ordinary skilled artisan would have a reasonable expectation of success for using CDA in combination with alum for enhanced neonatal immunization. It is also noted that the instant claims recite administering “one or more adjuvants, wherein at least one of the one or more adjuvants is a compound according to formula (I)” as well as the transitional phrase “comprising”, which can include any additional, unrecited elements (see MPEP 2111.03 I). Therefore, although Applicant argues the use of CDA alone for neonatal immunization, the applied Borriello reference is still within scope of the claims because Borriello discloses a combination of cGAMP and alum for neonatal immunization, and the claims allow for one or more adjuvants to be administered.
Second, in regards to Applicant’s showing of unexpected results, MPEP 716.02(e) provides guidance that the showing of unexpected results must be compared to the closest prior art.
Here, the closest prior art is Borriello, which demonstrates that Flublok immunization formulated with a combination of a cyclic dinucleotide STING agonist (cGAMP) and alum (Alhydrogel) enhanced rHA-specific IgG2a/c titers ~400 fold in newborn mice.
While Applicant has demonstrated that CDA alone as an adjuvant increased antibody titer significantly more than an R848 adjuvant as demonstrated in FIG. 3 for neonate mice, Applicant has not compared their CDA adjuvant results to the closest prior art (Borriello), which demonstrates the use of a combination of cGAMP and alum as adjuvants for neonatal immunization. Therefore, a comparison that is representative to the Borriello composition such as a comparison to a combination of CDA and alum is necessary in order to determine if Applicant has demonstrated an unexpected result to rebut a prima facie case of obviousness over Borriello.
Furthermore, it is noted that instant claim 1 recites administering “one or more adjuvants, wherein at least one of the one or more adjuvants is a compound according to formula (I)” as well as the transitional phrase “comprising”, which can include any additional, unrecited elements (see MPEP 2111.03 I). Therefore, a combination of a cyclic dinucleotide and other adjuvants such as the alum demonstrated in Borriello is within scope of the instant claims. Additionally, it is noted that if Applicant were to amend the claims such that CDA is the sole adjuvant administered, then these amendments would be consistent with Applicant’s arguments and may overcome the instant rejections of record provided that Applicant also demonstrates a sufficient showing of unexpected results over the closest prior art (Borriello) as discussed above.
Lastly, MPEP 716.02 (d) provides guidance that the showing of unexpected results must be commensurate in scope with the claimed invention.
Here, the recited formula (I) in instant claim 1 allows for several cyclic dinucleotide structures such as CDA, c-di-IMP, c-IAMP, etc. that can be administered. However, Applicant has only provided evidence of using CDA alone as an adjuvant for enhanced neonatal vaccination and has not demonstrated or provided a sufficient explanation that other cyclic dinucleotides that meet the structure of formula (I) will also have the alleged showing of unexpected results.
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.
Claims 1, 3, 8-14, and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,881,726 (‘726) in view of Borriello et al. (Frontiers in Immunology, 2017 in PTO-892 dated 11/17/2025).
Claim 1 of ‘726 recites an immunogenic composition comprising a) a hepatitis C virus (HCV) E1 polypeptide, an HCV E2 polypeptide, or an HCV E1/E2 heterodimer; and b) a cyclic dinucleotide (CDN). Claim 5 of ‘726 recites that the CDN is c-diGMP, c-diAMP, c-dilMP, c-dXMP, c-GpAp, c-Gplp, c-GpXp, c-Aplp, c-ApXp, or c-lpXp. Claims 11-12 of ‘762 recites a method of inducing an immune response to HCV in an individual, the method comprising administering an effective amount of the recited immunogenic composition, and further recites that the administering is via intramuscular or intranasal administration.
The difference between the claims of ‘726 and the claimed invention is that the claims of ‘726 do not recite administering to an individual that is an unborn child, a neonate, or an infant.
The teachings of Borriello are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have further included the alum disclosed in Borriello into the composition of ‘726 and further administer this composition to a neonate as disclosed in Borriello to arrive at the claimed invention.
One of ordinary skill in the art would have combined prior art elements according to known methods to yield predictable results and would have a reasonable expectation of success in doing so because Borriello provides guidance that cyclic dinucleotides including c-di-AMP and cGAMP are STING agonists that induce immune responses and further demonstrates the use of a STING agonist cGAMP in combination with alum as adjuvants for enhanced early life immunization, which suggests that a combination of alternative cyclic dinucleotide STING agonists such as c-di-AMP and alum would also result in the same enhanced adjuvant effect for early life immunization.
In regards to instant claim 21, the recited kit merely serves as a support and does not have a functional relationship to the recited formulation. Therefore, the recited kit is owed no patentable weight, and the recited formulation is rendered obvious as discussed above. MPEP 2111.05 recites “"[O]nce it is determined that the limitation is directed to printed matter, [the examiner] must then determine if the matter is functionally or structurally related to the associated physical substrate, and only if the answer is ‘no’ is the printed matter owed no patentable weight." And MPEP 2111.05 I. B recites “Where a product merely serves as a support for printed matter, no functional relationship exists.”
Claims 1, 3, 8-14, and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,576,968 (‘968) in view of Borriello et al. (Frontiers in Immunology, 2017 in PTO-892 dated 11/17/2025).
Claim 1 of ‘968 recites a method of inducing an immune response to an antigen in an individual, the method comprising administering to the individual: a) one or more nucleic acids comprising nucleotide sequences encoding a hepatitis C virus (HCV) E1 polypeptide, an HCV E2 polypeptide, or an HCV E1/E2 heterodimer; and b) a cyclic dinucleotide (CDN). Claim 5 of ‘968 recites that the CDN is c-diGMP, c-diAMP, c-dilMP, c-dXMP, c-GpAp, c-Gplp, c-GpXp, c-Aplp, c-ApXp, or c-lpXp. Claims 12 of ‘968 recites that the administering is via intramuscular or intranasal administration.
The difference between the claims of ‘968 and the claimed invention is that the claims of ‘968 do not recite administering to an individual that is an unborn child, a neonate, or an infant.
The teachings of Borriello are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have further included the alum disclosed in Borriello into the method of ‘968 and further administer to a neonate as disclosed in Borriello to arrive at the claimed invention.
One of ordinary skill in the art would have combined prior art elements according to known methods to yield predictable results and would have a reasonable expectation of success in doing so because Borriello provides guidance that cyclic dinucleotides including c-di-AMP and cGAMP are STING agonists that induce immune responses and further demonstrates the use of a STING agonist cGAMP in combination with alum as adjuvants for enhanced early life immunization, which suggests that a combination of alternative cyclic dinucleotide STING agonists such as c-di-AMP and alum would also result in the same enhanced adjuvant effect for early life immunization.
In regards to instant claim 21, the recited kit merely serves as a support and does not have a functional relationship to the recited formulation. Therefore, the recited kit is owed no patentable weight, and the recited formulation is rendered obvious as discussed above. MPEP 2111.05 recites “"[O]nce it is determined that the limitation is directed to printed matter, [the examiner] must then determine if the matter is functionally or structurally related to the associated physical substrate, and only if the answer is ‘no’ is the printed matter owed no patentable weight." And MPEP 2111.05 I. B recites “Where a product merely serves as a support for printed matter, no functional relationship exists.”
Claims 1, 3, 8-14, and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 12,042,536 (‘536) in view of Borriello et al. (Frontiers in Immunology, 2017 in PTO-892 dated 11/17/2025).
Claim 1 of ‘536 recites an immunogenic composition comprising a) a cyclic dinucleotide (CDN); and b) a hepatitis C virus (HCV) E1/E2 heterodimer; and c) a heterologous polypeptide comprising a T-cell epitope present in an HCV protein other than E1 and E2. Claim 5 of ‘536 recites that the CDN is c-diGMP, c-diAMP, c-dilMP, c-dXMP, c-GpAp, c-Gplp, c-GpXp, c-Aplp, c-ApXp, or c-lpXp. Claims 11-12 of ‘536 recites a method of inducing an immune response to HCV in an individual, the method comprising administering an effective amount of the recited immunogenic composition, and further recites that the administering is via intramuscular or intranasal administration.
The difference between the claims of ‘536 and the claimed invention is that the claims of ‘536 do not recite administering to an individual that is an unborn child, a neonate, or an infant.
The teachings of Borriello are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have further included the alum disclosed in Borriello into the composition of ‘536 and further administer this composition to a neonate as disclosed in Borriello to arrive at the claimed invention.
One of ordinary skill in the art would have combined prior art elements according to known methods to yield predictable results and would have a reasonable expectation of success in doing so because Borriello provides guidance that cyclic dinucleotides including c-di-AMP and cGAMP are STING agonists that induce immune responses and further demonstrates the use of a STING agonist cGAMP in combination with alum as adjuvants for enhanced early life immunization, which suggests that a combination of alternative cyclic dinucleotide STING agonists such as c-di-AMP and alum would also result in the same enhanced adjuvant effect for early life immunization.
In regards to instant claim 21, the recited kit merely serves as a support and does not have a functional relationship to the recited formulation. Therefore, the recited kit is owed no patentable weight, and the recited formulation is rendered obvious as discussed above. MPEP 2111.05 recites “"[O]nce it is determined that the limitation is directed to printed matter, [the examiner] must then determine if the matter is functionally or structurally related to the associated physical substrate, and only if the answer is ‘no’ is the printed matter owed no patentable weight." And MPEP 2111.05 I. B recites “Where a product merely serves as a support for printed matter, no functional relationship exists.”
Claims 1, 3, 8-14, and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 9,597,391 (‘391) in view of Borriello et al. (Frontiers in Immunology, 2017 in PTO-892 dated 11/17/2025).
Claim 1 of ‘391 recites a method of enhancing an immune response in a subject in need thereof for eliciting a balanced Th1/Th2 response, comprising the step of administering, as an adjuvant with one or more different antigens, to the subject at least one compound according to the recited formula (I). Claim 4 of ‘391 recites that the compound according to formula (I) is a cyclic bis(3′-5′)diadenylic acid. Claims 8 and 10 of ‘381 recite that the adjuvant is administered by either intranasal or intramuscular administration.
The difference between the claims of ‘391 and the claimed invention is that the claims of ‘391 do not recite administering to an individual that is an unborn child, a neonate, or an infant.
The teachings of Borriello are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have further included the alum disclosed in Borriello into the method of ‘391 and further administer to a neonate as disclosed in Borriello to arrive at the claimed invention.
One of ordinary skill in the art would have combined prior art elements according to known methods to yield predictable results and would have a reasonable expectation of success in doing so because Borriello provides guidance that cyclic dinucleotides including c-di-AMP and cGAMP are STING agonists that induce immune responses and further demonstrates the use of a STING agonist cGAMP in combination with alum as adjuvants for enhanced early life immunization, which suggests that a combination of alternative cyclic dinucleotide STING agonists such as c-di-AMP and alum would also result in the same enhanced adjuvant effect for early life immunization.
In regards to instant claim 21, the recited kit merely serves as a support and does not have a functional relationship to the recited formulation. Therefore, the recited kit is owed no patentable weight, and the recited formulation is rendered obvious as discussed above. MPEP 2111.05 recites “"[O]nce it is determined that the limitation is directed to printed matter, [the examiner] must then determine if the matter is functionally or structurally related to the associated physical substrate, and only if the answer is ‘no’ is the printed matter owed no patentable weight." And MPEP 2111.05 I. B recites “Where a product merely serves as a support for printed matter, no functional relationship exists.”
Claims 1, 3, 8-14, and 17-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of copending Application No. 19/168,627 (‘627) in view of Borriello et al. (Frontiers in Immunology, 2017 in PTO-892 dated 11/17/2025).
The claims of ‘627 recite a method for improving the immune response of a subject in need thereof with underperforming immune systems due to immune-deficiency caused by age, chronic condition or due to medical or therapeutic interventions, characterized by low or poor responsiveness or non-responsiveness to vaccine antigens or under-performing immune response to pathogens, comprising administering to the subject a cyclic dinucleotide (CDN) (claim 1). The claims of ‘627 recite the CDN is administered in combination with a biological response modifier such as hepatitis B nucleocapsid antigen (HBcAg) (claims 3-4). The claims of ‘627 recite that the CDN can be CDA, c-di-GMP, and others (claim 7). The claims of ‘627 recite that the CDN is administered by intranasal or others (claim 8). The claims of ‘627 recite that the administration is performed for or as part of prophylactic or therapeutic vaccination (claim 19) and to immunize an individual with a reduced capacity of response to RNA viruses and variants thereof (claim 17).
The difference between the claims of ‘627 and the claimed invention is that the claims of ‘627 do not recite administering to an individual that is an unborn child, a neonate, or an infant.
The teachings of Borriello are as described above.
It would have been prima facie obvious before the effective filing date of the claimed invention to have further included the alum disclosed in Borriello into the method of ‘627 and further administer to a neonate as disclosed in Borriello to arrive at the claimed invention.
One of ordinary skill in the art would have combined prior art elements according to known methods to yield predictable results and would have a reasonable expectation of success in doing so because Borriello provides guidance that cyclic dinucleotides including c-di-AMP and cGAMP are STING agonists that induce immune responses and further demonstrates the use of a STING agonist cGAMP in combination with alum as adjuvants for enhanced early life immunization, which suggests that a combination of alternative cyclic dinucleotide STING agonists such as c-di-AMP and alum would also result in the same enhanced adjuvant effect for early life immunization.
In regards to instant claims 19-20, it would have also been prima facie obvious before the effective filing date of the claimed invention to modified the mode of administration recited in the combination of the claims of ‘627 and Borriello as described above to an intramuscular administration as disclosed in Borriello to arrive at the claimed invention.
One of ordinary skill in the art would have combined prior art elements according to known methods to yield predictable results and would have a reasonable expectation of success in doing so because Borriello provides guidance that a similar CDN adjuvanted vaccine composition is suitable for intramuscular administration.
In regards to instant claim 21, the recited kit merely serves as a support and does not have a functional relationship to the recited formulation. Therefore, the recited kit is owed no patentable weight, and the recited formulation is rendered obvious as discussed above. MPEP 2111.05 recites “"[O]nce it is determined that the limitation is directed to printed matter, [the examiner] must then determine if the matter is functionally or structurally related to the associated physical substrate, and only if the answer is ‘no’ is the printed matter owed no patentable weight." And MPEP 2111.05 I. B recites “Where a product merely serves as a support for printed matter, no functional relationship exists.”
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant’s arguments filed on 05/11/2026 have been fully considered but were not persuasive.
Applicant states in regards to the nonstatutory double patenting rejections that the application of CDA to specific neonatal populations leads to surprisingly unexpected results. Applicant further states that the cGAMP of Borriello alone did not raise any immune response in newborn mice. Therefore, Applicant states that the skilled person would not consider that the family of CDN would represent suitable adjuvants in neonatal immunization. Applicant states in contrast, the discovery of CDA specifically provides this unexpected potent and protective immune response that is not taught or suggest in the prior art and constitutes a non-obvious improvement.
Applicant’s arguments described above were not found persuasive because the amended nonstatutory double patenting rejections relies on further including the alum of Borriello with a recited CDN such as the CDA of the reference applications and not necessarily using the recited CDN alone as the adjuvant. Here, Borriello provides guidance that cyclic dinucleotides including c-di-AMP and cGAMP are STING agonists that induce immune responses and further demonstrates the use of a STING agonist cGAMP in combination with alum as adjuvants for enhanced early life immunization, which suggests that a combination of alternative cyclic dinucleotide STING agonists such as c-di-AMP and alum would also result in the same enhanced adjuvant effect for early life immunization.
Furthermore, in regards to Applicant’s arguments of a showing of unexpected results, these arguments are analogous with the arguments made regarding the rejections under 35 USC 103 and are also not persuasive for the same reasons as discussed in detail above.
Conclusion
No claim is found allowable.
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/D.H.C./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
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