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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 Apr. 6, 2026 has been entered.
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on Apr. 6, 2026. Claims 1-19 are pending and currently examined.
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 of this title, 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.
(Previous Rejection - Maintained) Claims 1, 2 and 5-19 are rejected under 35 U.S.C. 103 as being unpatentable over Bedu-Addo et al. (US 2015/0110823 A1, published on Apr. 23, 2015; also published as WO 2013/039989 A1 on Mar. 21, 2013) and Mailere et al. (US 2004/0170644 A1, published on Sep. 2, 2004).
These claims require four different peptides comprising SEQ ID NOs: 5, 9, 10 and 11, respectively.
SEQ ID NO: 5 (GQAEPDRAHYNIVTF) correlates to aa 43-57 of HPV16 E7 protein. SEQ ID NO: 9 (MHGDTPTLHEYMLDLQPETT) correlates to aa 1-20 of HPV16 E7. SEQ ID NO: 10 (LLMGTLGIVCPICSQKP) correlates to aa 10-26 of HPV16 E7. SEQ ID NO: 11 (ELQTTIHDIILECVYCKQQLL) correlates aa 25-45 of HPV16 E6.
Bedu-Addo teaches vaccine formulations comprising at least one peptide antigen assembly and at least one adjuvant. The disclosure also provides methods of inducing an immune response in a mammal and methods of treating a disease in a mammal utilizing the vaccine formulations. See Abstract and claims 1-7.
Specifically, Bedu-Addo teaches that the vaccine formulation may comprise as adjuvant cationic lipid such DOTAP, DOTMA, DOEPC, or combinations thereof, and that the vaccine formulation may comprise at least one HPV16 E6 and/or E7 peptide antigen selected from the group consisting of RAHYNIVTF (SEQ. ID. NO: 1), GQAEPDRAHYNIVTF (SEQ. ID. NO: 2), KSSGQAEPDRAHYNIVTF (SEQ. ID. NO: 3), YMLDLQPETT (SEQ. ID. NO: 4), KSSYMLDLQPETT (SEQ. ID. NO: 5), KSSMHGDTPTLHEYMLDLQPETT (SEQ. ID. NO: 6), KSSLLMGTLGIVCPICSQKP (SEQ. ID. NO: 7), KVPRNQDWL (SEQ. ID. NO: 8), SYVDFFVWL (SEQ. ID. NO: 9), KYICNSSCM (SEQ. ID. NO: 10), and KSSKVPRNQDWL (SEQ. ID. NO: 11). See e.g. claims 4, 18, 28 and 29. It teaches that the vaccine formulation enhances CD8+ T cell immune response. Here, SEQ ID NOs: 2, 6 and 7 of Bedu-Addo comprise SEQ ID NOs: 5 (GQAEPDRAHYNIVTF), 9 (MHGDTPTLHEYMLDLQPETT) and 10 (LLMGTLGIVCPICSQKP) of the instant application, respectively.
Accordingly, Bedu-Addo teaches a vaccine composition comprising at least one antigen peptide comprising sequences of SEQ ID NO: 5, 9 or 10 of instant invention and an adjuvant comprising cationic lipid such DOTAP, DOTMA, DOEPC. As to the HLA binding properties, Bedu-Addo teaches antigen peptides comprising the same amino acid sequences as claimed, these peptides are expected to have the same HLA-binding properties as claimed. However, Bedu-Addo is silent on an HPV16 antigen peptide comprising SEQ ID NO: 11.
Mailere teaches an invention concerning a mixture of peptides derived from the E6 and/or E7 proteins of a papillomavirus involved in cervix of uterus cancer, as well as immunogenic compositions comprising the peptides capable of stimulating the production of anti-HPV T CD4+ lymphocytes in vivo and hence useful for vaccination against HPV-associated cancers. See e.g. Abstract. Mailere teaches a series of T cell epitopes in HPV16 E6 and E7 identified in patients. See e.g. [0035] and Table II. Peptides E6:24-45 and E6:22-51 disclosed in Table II comprises the HPV16 E6 aa-25-45 (corresponding to SEQ ID NO: 11). Additionally, Mailere specifically discloses a 32-aa HPV16 E6 peptide, SEQ ID NO: 9, which comprises the claimed SEQ ID NO: 11.
It would have been prima facie obvious for one of ordinary skill in the art at the time of invention to test different combinations of peptide antigens taught in Bedu-Addo and Mailere to arrive at the invention as claimed, i.e., a combination comprising three peptides, SEQ ID NOs: 2, 6 and 7 of Bedu-Addo (comprising instant SEQ ID NOs: 5 (GQAEPDRAHYNIVTF), 9 (MHGDTPTLHEYMLDLQPETT) and 10 (LLMGTLGIVCPICSQKP) of the instant application, respectively), and peptide E6:24-45 or E6:22-51 of Mailere (comprising instant SEQ ID NO: 11). One would have been motivated to do so to combine the antigenic epitopes of the respective peptides in a potential vaccine.
Regarding claim 5, Bedu-Addo discloses at least peptides of SEQ ID NOs: 5-7 which comprise YMLDLQPETT (SEQ ID NO: 14 recited in instant claim 5).
Regarding claims 7, 12 and 17, Bedu-Addo teaches R-DOTAP. See e.g. [0025].
Regarding claim 8, Bedu-Addo teaches that peptide antigens are encapsulated in lipid micelles. See e.g. [0218-0221].
Regarding claims 9, 13, 14, 18 and 19, Bedu-Addo teaches antigen peptides that comprise the same amino acid sequences as claimed, they are expected to have the same properties in HLA-binding, CD8+ T cell induction and tumor treating effects.
(Previous Rejection - Maintained) Claims 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over Bedu-Addo et al. (US 2015/0110823 A1, published on Apr. 23, 2015; also published as WO 2013/039989 A1 on Mar. 21, 2013) and Mailere et al. (US 2004/0170644 A1, published on Sep. 2, 2004), as applied above, in view of Van der Burg et al. (US 2010/0189742 A1, published on Jul. 29, 2010).
Claims 3-4 specify that the peptide antigens are conjugated to each other, and claim 4 further specifies comprising a spacer.
Relevance of Bedu-Addo and Mailere is set forth above. However, they are silent on if the peptide antigens can be conjugated to each other with or without a spacer.
Van der Burg teaches immunogenic compositions comprising HPV antigen epitope peptides of E6 and/or E7. See Abstract. It teaches that two or more peptides and/or epitopes of the invention can be arranged as beads-on-string, whereby the peptides and/or epitopes of the invention (the beads) are linked directly together and/or are linked through linker sequences. See e.g. [0061].
It would have been prima facie obvious for one of ordinary skill in the art at the time of invention to combine the teachings of Bedu-Addo and Van der Burg. One would have been motivated to do so, e.g., to facilitate expression of the involved peptides in one fusion peptide, as taught in Van der Burg.
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 - Maintained) Claims 1-19 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-10 of US patent 11401306 alone or in view of the prior art references cited in the 103 rejections above.
Although the conflicting claims are not identical, they are not patentably distinct from each other. Both sets of claims encompass an immunogenic composition comprising HPV16 E6 and/or E7 peptides and a cationic lipid as adjuvant.
The reference claims anticipate instant claims 1, 2 and 5-19.
For instant claims 3 and 4, it would have been prima facie obvious for one of ordinary skill in the art at the time of invention to combine the teachings of Bedu-Addo, Mailere and Van der Burg to arrive at the instant claims 3-4 from the reference claims.
Response to Applicant’s Arguments
Applicant’s arguments and Declaration filed on Apr. 6, 2026 are fully considered and addressed as follows.
To the 103 rejections, Applicant argues on the following aspects:
(1) Neither Bedu-Addo nor Mailere disclose all of possible peptides that can be used in an immunogenic composition, and there was no finite set of combinations of peptides which would have been “obvious to try” with a reasonable expectation of success.
(2) The present application demonstrates that not all E6/E7 peptide fragments, even closely adjacent or minimally altered fragments, are immunologically active; and the Final OA’s inherency theory – that HLA binding breath across five supertypes is simply inherent to “immunogenic” E6/E7 peptides – cannot stand.
(3) Neither Bedu-Addo nor Mailere disclose the peptide of SEQ ID NO: 11. Mailere discloses a peptide of E6 aa 14-45 (Marlere SEQ ID NO: 9) has 11 additional amino acid compared to claimed SEQ ID NO: 11, and one of skill in the art could not have predicted the SEQ ID NO: 11 would have similar, indeed any, immunogenic properties.
(4) Bedu-Addo and Mailere rely on different approaches in studying the HPV peptides and are silent regarding to HLA class I breadth across the five supertypes.
(5) As discussed in the Declaration, third party efforts employing overlapping long peptides that cover the entire E6 and E7 protein sequences have not consistently demonstrated clinical benefit in relevant settings, underscoring that “more overlap” is not predictive of efficacy. By contrast, Applicant’s four-peptide, non-overlapping design – engineered for five-supertype HLA class I breadth and delivered with a cationic lipid – has produced strong HPV-specific T-cell responses in humans without HLA-type restriction.
Applicant’s arguments are not persuasive.
Regarding arguments (1) and (3), Bedu-Addo and Mailere teach a finite number of putatively immunogenic peptides derived from the sequences of HPV16 E6 and E7, including peptides that comprises the claimed sequences of SEQ ID NOs: 5 and 9-10. Bedu-Addo teaches including HPV peptides comprising the instant SEQ ID NOs: 5, 9 and/or 10 in immunogenic compositions that induce CD8+ - T-cell responses. Mailere teaches a finite number of HPV16 E6 and E7 peptides that contain T-cell epitopes, including two peptides comprising the instant SEQ ID NO: 11. See discussions in the art rejection above. Therefore, based on the teachings Bedu-Addo and Mailere, one of skill in the art would have known that peptides comprising the instant sequences are potential choices as they are known to contain T-cell epitopes, and do not need to test all possible peptides that could be derived from the E6 and E7 proteins.
Regarding arguments (2) and (4), Bedu-Addo and Mailere disclose peptides that comprise the same amino acid sequences as those of instantly claimed peptide sequences. If the instantly claimed peptides have the immunogenic property as claimed (note: the amended claims require the peptide bind and activate HLA class I proteins), it is reasonable to expect that the peptides comprising the same sequences would have the same binding activities (i.e., binding and activating HLA class I proteins, an activity associated with CD8+ T-cell epitopes).
Regarding argument (5), combined teachings of Bedu-Addo and Mailere reveal a panel of limited number of HPV16 E6 and E7 peptides, including peptides comprising the 4 recited sequences of the instant application, having T-cell epitopes that can be included in potential vaccine compositions, individually or in combinations. One of skill in the art would have found it obvious to test them, especially their combination effects, in routine experimental optimization and arrive at the invention as claimed.
It is noted that using the word “comprise” the claims are not limited in a composition containing only 4 of the cited peptide sequences. On the contrary, the claimed invention encompasses a combination of all the peptides disclosed in Bedu-Addo and Mailere, as long as peptides comprising the 4 recited sequences are included.
As to arguments about unpredictability, it is reasonably predictable that immunogenic properties of any peptides or combination thereof disclosed in Bedu-Addo and Mailere can be tested by routine immunological procedures.
Additionally, Applicant appears to have argued that results produced by the claimed invention are unexpected. As an initial matter, “the burden of showing unexpected results rests on he who asserts them. Thus it is not enough to show that results are obtained which differ from those obtained in the prior art: that difference must be shown to be an unexpected difference.” In re Klosak, 455 F.2d 1077, 1080 (CCPA 1972) (citation omitted). Moreover, “[i]t is well settled that unexpected results must be established by factual evidence. Mere argument or conclusory statements in the specification does not suffice.” In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984) (citation omitted). Applicant’s attention is directed to MPEP 716.02(b)-(e) for how unexpected results can be established.
To the obviousness-type double patenting rejection, Applicant argues that the claims as amended are patentably distinct for the same reasons described in the response to the 103 rejections and request the rejection be withdrawn.
Applicant’s argument is not persuasive for the same reasons described in the Examiner’s response to Applicant’s arguments above. Additionally, much of the ODP rejection is based on the anticipation analysis, not the obviousness analysis. A rebuttal based on arguments against obviousness is not germane. See MPEP 804.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIANXIANG 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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