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 .
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on Jul. 31, 2026. Claims 1-18 are pending and currently examined.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
(Previous Rejection – Withdrawn) Claims 1-15 were rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
This rejection is withdrawn in view of the amendment filed on Jul. 31, 2026.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(Previous Rejection – Withdrawn) Claims 1-15 were rejected under 35 U.S.C. 102 as being anticipated by Wang et al. (US 10,052,378 B2, date of patent Aug. 21, 2018).
This rejection is withdrawn in view of the amendment filed on Jul. 31, 2026. Applicant’s arguments regarding this rejection are moot.
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.
Claims 1-18 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (US 10,052,378 B2, date of patent Aug. 21, 2018), in view of Doi et al. (US 2022/0401540 A1, published on Dec. 22, 2022; PCT filed on Nov. 26, 2020), Sun et al. (Journal of Cancer 2016, Vol. 7, pp241-250), Kuo et al. (Sci Rep 10, 20085 (2020)), and Soema et al. (European Journal of Pharmaceutics and Biopharmaceutics 94 (2015) 251–263).
Base claim 1, as amended, is directed to a composition comprising CpG ODN and an aluminum adjuvant that works together with the immunomodulatory CpG ODN, wherein the CpG ODN comprises or consists of the nucleotide sequence set forth in any one of SEQ ID NOs: 2-4, wherein at least one nucleotide in the nucleotide sequence is a chemical modified nucleotide having a structure of formula (I).
Formula (I) reads on a phosphorothioate nucleotide (in which the Y is S, R may be H, and R1 may be OH). Thus, the claimed CpG ODN reads on synthetic phosphorothioate oligonucleotides (PS-oligos) comprising one of SEQ ID NOs: 2-4.
Wang teaches an invention relating to a pharmaceutical composition for inducing immune response in a subject, comprising: (a) an antigen with a concentration ranging from 1 μg/ml to 100 μg/ml; (b) CpG oligonucleotides having a sequence of 5'-tcgacgttcgtcgttcgtcgttc-3', with a concentration ranging from 25 μg/ml to 500 μg/ml, and (c) an aluminum adjuvant with a concentration ranging from 25 μg/ml to 500 μg/ml. Such pharmaceutical composition can induce or boost immune response against antigen in the subject. See Abstract. Here, the CpG ODN sequence is identical to instant SEQ ID NO: 1, but not the claimed SEQ ID NOs: 2-4.
Wang teaches that chemical modifications can be used in the invention, such as modification of CpG-ODN backbone, including but not limited to modification of backbone with phosphorothioate and thereby obtaining phosphorothioate backbone; that such backbone is a stable nucleic acid molecular sugar-phosphate backbone, in which, on the bond of at least one nucleotide, oxygen in phosphate group that is not bridged is substituted by sulphur, alternatively, on the bond of each nucleotide or every other nucleotide, oxygen in phosphate group that is not bridged is substituted by sulphur. See column 6, lines 4-14. Wang teaches that aluminum adjuvant used in the invention can be of aluminium hydroxide, aluminium phosphate and aluminium sulfate. See column 6, line 24-34.
Accordingly, Wang teaches a composition comprising a CpG ODN and an aluminum adjuvant, wherein the CpG ODN has the same sequence as the instant SEQ ID NO: 1, and wherein the CpG ODN can contain modified nucleotide, such as phosphorothioate nucleotide (in which Y in Formula (I) is S). Wang teaches that the ODN backbone can be either completely or partially phosphorothioated. However, Wang is silent on CpG ODN with any one of SEQ ID NOs: 2-4, as currently claimed.
Doi teaches an invention relating to cancer vaccine comprising a pharmaceutical composition comprising a Toll-like receptor (TLR) agonist, LAG-3 protein, a variant thereof or a derivative thereof, at least one immunogenic agent, and an immune checkpoint inhibitor are administered in combination. See Abstract. Doi teaches that TLR agonists of the invention can be the TLR9 agonist include CpG ODN such as CpG, CpG-28, CpG-685 (GNKG168), CpG-1826, CpG-7909 (PF-3512676, agatolimod, Promune (registered trademark)), ODN1585, IMO-2125, IMO-2055 (EMD1201081), ISS1018, MGN-1703, MGN-1706, AVE0675, QAX-935, SAR-21609, SD-101, and DIMS0150. See [0258].
Sun teaches a study for investigating whether C-class CpG ODN (CpG ODN-685) could facilitate tumor cell lysate to induce vigorous anti-tumor activity against tumors in mice both prophylactically and therapeutically. See Abstract. Sun teaches that the CpG 685 sequence is 5’-TCGTCGACGTCGTTCGTTCTC-3’. See page 242, right column, para 3.
Kuo teaches in developing a COVID-19 vaccine, the authors applied technology previously used for MERS-CoV to produce a prefusion-stabilized SARS-CoV-2 spike protein, S-2P. To enhance immunogenicity and mitigate the potential vaccine-induced immunopathology, CpG 1018, a Th1-biasing synthetic toll-like receptor 9 (TLR9) agonist was selected as an adjuvant candidate. S-2P in combination with CpG 1018 and aluminum hydroxide (alum) was found to be the most potent immunogen and induced high titer of neutralizing antibodies in sera of immunized mice against pseudotyped lentivirus reporter or live wild-type SARS-CoV-2. In addition, the antibodies elicited were able to cross-neutralize pseudovirus containing the spike protein of the D614G variant, indicating the potential for broad spectrum protection. A marked Th1 dominant response was noted from cytokines secreted by splenocytes of mice immunized with CpG 1018 and alum. No vaccine-related serious adverse effects were found in the dose-ranging study in rats administered single- or two-dose regimens of S-2P combined with CpG 1018 alone or CpG 1018 with alum. These data support continued development of CHO-derived S-2P formulated with CpG 1018 and alum as a candidate vaccine to prevent COVID-19 disease. See Abstract.
Soema review the development of influenza vaccines. It teaches that current seasonal trivalent influenza vaccine (TIV) formulations contain either inactivated influenza antigens or live attenuated influenza viruses, derived from two influenza A strains and one influenza B strain, and that next to TIV formulations, quadrivalent influenza vaccine (QIV) formulations have entered the market recently, which adds an additional influenza B strain. See page 253, right column, para 2. Soema teaches that various adjuvants are used in influenza vaccines, including TLR9 agonist CpG oligodeoxynucleotide (ODN). See Table 2.
Accordingly, Doi and Sun together teach a TLR9 agonist CpG ODN 685 with the sequence of 5’-TCGTCGACGTCGTTCGTTCTC-3’, identical to the instant SEQ ID NO: 3, and its application as a vaccine adjuvant; Kuo teaches that TLR9 agonist in the form of CpG ODN can be used as adjuvant to promoter immune response to SARS-CoV-2 antigens; and Soema teaches that quadrivalent influenza vaccines are developed at the time of invention and that CpG ODNs can be used as adjuvant for influenza vaccines.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the current invention to introduce the TLR9 agonist CpG ODN 685 with the sequence of 5’-TCGTCGACGTCGTTCGTTCTC-3’, disclosed in Doi and Sun, into the study of Wang and arrive at the invention as claimed. One would have been motivated to do so, e.g., to evaluate the adjuvant effect of CpG ODN 685 in the study of Wang.
Regarding claims 7 and 12, Wang teaches that the antigen of the composition can be a hepatitis B virus antigen, making it a potential hepatitis B vaccine. See column 7.
Regarding claim 15, the composition of Wang is inherently prepared by mixing the specified ingredients.
Regarding claims 16 and 18, Kuo and Soema teach that CpG ODNs can be used as adjuvants in vaccines for SARS-CoV-2 and influenza virus.
Regarding claim 17, one of skill in the art would have readily expected that claimed amount of antigens in vaccine formulation can be determined via routine experimental optimization. This is especially true when the claimed range is for an antigen that is not specified.
Double Patenting Rejection
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/forms/. The 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
(Previous Rejection – Withdrawn) Claims 1-15 were rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-8 of US Patent 10,052,378 B2 (Wang et al. (US 10,052,378 B2, date of patent Aug. 21, 2018), as applied in the art rejection above).
This rejection is withdrawn in view of the amendment filed on Jul. 31, 2026.
(New Rejection – Necessitated by Amendment) Claims 1-18 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-8 of US Patent 10,052,378 B2 in view Wang et al. (US 10,052,378 B2, date of patent Aug. 21, 2018), Doi et al. (US 2022/0401540 A1, published on Dec. 22, 2022; PCT filed on Nov. 26, 2020), Sun et al. (Journal of Cancer 2016, Vol. 7, pp241-250), Kuo et al. (Sci Rep 10, 20085 (2020)), and Soema et al. (European Journal of Pharmaceutics and Biopharmaceutics 94 (2015) 251–263), as applied in the art rejection above.
Although the conflicting claims are not identical, they are not patentably distinct from each other. Both sets of claims encompass a composition comprising a CpG ODN and an additional adjuvant agent that can be an aluminum adjuvant. The differences include: (1) the patented claims require an CpG ODN with SEQ ID NO: 1 while the instant claims require an CpG ODN with one of SEQ ID NOs: 2-4, (2) the patented claims require an hepatis C related antigen while the instant claims are either silent on antigens or specify different antigen, (3) the patented claims are silent on the modification of the CpG ODN, and (4) the patented claims require specific ranges for the components which the instant claims are either generic or require slightly different ranges.
As indicated in the 103 rejection above, the patent is now considered as prior art. Therefore, it would have been prima facie obvious for one of ordinary skill in the art to modify the CpG ODN of the patented invention based on the teachings of itself in combination of the other cited prior art references. See discussion in the 103 rejection. Such modifications would arrive at an invention that is encompassed by the instant invention.
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 extension fee 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 NIANXIANG (NICK) ZOU whose telephone number is (571)272-2850. The examiner can normally be reached on Monday - Friday, 8:30 am - 5:00 pm, EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MICHAEL ALLEN, on (571) 270-3497, can be reached. 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.
/NIANXIANG ZOU/
Primary Examiner, Art Unit 1671
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