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 Sep. 26, 2025. Claims 10-21 are pending and currently examined.
Sequence Analysis
Alignment between SEQ ID NO: 20 and a simple direct fusion construct of HPV52 E6 and E7 antigens (52E6E7) is shown below:
Score
Expect
Method
Identities
Positives
Gaps
Frame
446 bits(1147)
1e-165()
Compositional matrix adjust.
225/251(90%)
229/251(91%)
15/251(5%)
SEQ20 19 FEDPATSGRTLHELCEVLEESVHEIRLQCVQCKKELQRREVYK---TDLRIVYRDNNPYG 75
FEDPAT RTLHELCEVLEESVHEIRLQCVQCKKELQRREVYK TDLRIVYRDNNPYG
52E6E7 2 FEDPATRPRTLHELCEVLEESVHEIRLQCVQCKKELQRREVYKFLFTDLRIVYRDNNPYG 61
Query 76 VCIMCLRFLSKISEYRHYQYSLYGKTLEERVRKPLSEITIRCIICQTPL-----ERHVNA 130
VCIMCLRFLSKISEYRHYQYSLYGKTLEERV++PLSEITIRCIICQTPL ERHVNA
Sbjct 62 VCIMCLRFLSKISEYRHYQYSLYGKTLEERVKRPLSEITIRCIICQTPLCPEEKERHVNA 121
Query 131 NKRFHNIMGRWTGRCSECWRPRPVTQVRGRKRRSRGDKATIKDYILDLQPETTDLHGYGQ 190
NKRFHNIMGRWTGRCSECWRPRPVTQV RGDKATIKDYILDLQPETTDLH Y Q
Sbjct 122 NKRFHNIMGRWTGRCSECWRPRPVTQV-------RGDKATIKDYILDLQPETTDLHCYEQ 174
Query 191 LGDSSDEEDTDGVDRPDGQAEQATSNYYIVTYCHSCDSTLRLCIHSTATDLRTLQQMLLG 250
LGDSSDEED DGVDRPDGQAEQAT NYYIVT C+SC+STLRLCIHSTATDLRTLQQMLLG
Sbjct 175 LGDSSDEEDIDGVDRPDGQAEQATDNYYIVTDCYSCNSTLRLCIHSTATDLRTLQQMLLG 234
Query 251 TLQVVCPGCAR 261
TLQVVCPGCAR
Sbjct 235 TLQVVCPGCAR 245
SEQ ID NO: 20 presents a fusion protein containing four parts: 1) a 18-aa IgE leader peptide sequence (MDWTWILFLVAAATRVHS), 2) a mutated HPV52 E6 sequence (underlined), 3) an endoproteolytic cleavage site (RGRKRRS), and 4) a mutated HPV52 E7 sequence (Italic).
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
(Previous Rejection – Withdrawn) Claims 10-20 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention. This rejection has the following grounds.
This rejection is withdrawn in view of the amendment filed on Sep. 26, 2025.
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 10 and 18 were rejected under 35 U.S.C. 102 as being anticipated by Yan et al. (Vaccine. 2009 January 14; 27(3): 431–440).
This rejection is withdrawn in view of the amendment filed on Sep. 26, 2025.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
(Previous Rejection – Withdrawn) Claims 10-15 and 18-21 were rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Cassetti et al. (US 2007/0275003 A1, published on Nov. 29, 2007) in view of GenBank: ABQ44353.1 (E6 protein [human papillomavirus 52]. Dated May 21, 2007) and GenBank: AEI61551.1 (E7 Protein [human papillomavirus 52]. Dated Jun. 27, 2011).
This rejection is withdrawn in view of the amendment filed on Sep. 26, 2025.
(Previous Rejection – Maintained) Claims 16-17 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Cassetti et al. (US 2007/0275003 A1, published on Nov. 29, 2007) in view of GenBank: ABQ44353.1 (E6 protein [human papillomavirus 52]. Dated May 21, 2007) and GenBank: AEI61551.1 (E7 Protein [human papillomavirus 52]. Dated Jun. 27, 2011), and further in view of Yan et al. (Vaccine. 2009 January 14; 27(3): 431–440). This rejection is extended to claims 10-15 and 18-21 as necessitated by amendment.
The base claim 10, as amended, is directed to a composition comprising at least one HPV52 E6-E7 fusion antigen; wherein the HPV52 E6-E7 fusion antigen is selected from the group consisting of SEQ ID NO:20, a peptide comprising a sequence that is at least 95% identical to SEQ ID NO:20, a peptide comprising a fragment of at least 244 amino acids of SEQ ID NO:20, and a peptide comprising a sequence that is at least 95% identical to a fragment of at least 244 amino acids of SEQ ID NO:20.
Claims 16-17 further specify that the HPV52 E6-E7 fusion antigen is at least 98% or at least 99% identical to SEQ ID NO: 20.
Relevance of Cassetti, GenBank: ABQ44353.1 and GenBank: AEI61551.1 is set forth in the withdrawn 103 rejection above in the previous Office action. Briefly, it would have been prima facie obvious to one of ordinary skill in the art at the time of invention to construct an HPV52 E6-E7 fusion antigen by linking the HPV52 E6 and E7 proteins in one fusion antigen based on teachings of Cassetti, GenBank: ABQ44353.1 and GenBank: AEI61551.1. As indicated above, a simple direct fusion construct of HPV52 E6 and E7, about 90% identical to SEQ ID NO: 20, would lack the IgE leader sequence, the endoproteolytic cleavage site, and the mutations abolishing the oncogenic sites.
Relevance of Yan is set forth in the withdrawn 102 rejection above in the previous Office action. Specifically, it teaches a HPV16 E6-E7 fusion antigen (ConE6E7) comprising the same IgE leader sequence (underlined), the same endoproteolytic cleavage site (underlined), and mutations abolishing the oncogenic sites of the HPV16 E6 and E7 proteins. Alignment between the claimed SEQ ID NO: 20 and ConE6E7 of Yan (GenBank accession number: FJ229356) is shown below:
Score Expect Method Identities Positives Gaps
343 bits(879)1e-124 Compositional matrix adjust. 168/264(64%) 204/264(77%) 5/264(1%)
SEQ20 1 MDWTWILFLVAAATRVHSFEDPATSGRTLHELCEVLEESVHEIRLQCVQCKKELQRREVY 60
MDWTWILFLVAAATRVHSF+DP SGR L +LC L+ ++H+I L+CV CK++L RREVY
ConE6E7 1 MDWTWILFLVAAATRVHSFQDPQESGRKLPQLCTELQTTIHDIILECVYCKQQLLRREVY 60
Query 61 KTDLRIVYRDNNPYGVCIMCLRFLSKISEYRHYQYSLYGKTLEERVRKPLSEITIRCIIC 120
DL IVYRD NPY VC CL+F SKISEYRHY YSLYG TLE++ KPL ++ IRCI C
Sbjct 61 DRDLCIVYRDGNPYAVCDKCLKFYSKISEYRHYCYSLYGTTLEQQYNKPLCDLLIRCINC 120
Query 121 QTPLERHVNANKRFHNIMGRWTGRCSECWRP---RPVTQVRGRKRRSRGDKATIKDYILD 177
Q PL+RH++ +RFHNI GRWTGRC C R R TQ+RGRKRRS GD T+ +Y+LD
Sbjct 121 QKPLQRHLDKKQRFHNIRGRWTGRCMSCCRSSRTRRETQLRGRKRRSHGDTPTLHEYMLD 180
Query 178 LQPETTDLHGYGQLGDSSDEEDTDGVDRPDGQAEQATSNYYIVTYCHSCDSTLRLCIHST 237
LQPETTDL+GYGQL DSS+EED +D P GQAE ++Y IVT+C CDSTLRLC+ ST
Sbjct 181 LQPETTDLYGYGQLNDSSEEEDE--IDGPAGQAEPDRAHYNIVTFCCKCDSTLRLCVQST 238
Query 238 ATDLRTLQQMLLGTLQVVCPGCAR 261
D+RTL+ +L+GTL +VCP C++
Sbjct 239 HVDIRTLEDLLMGTLGIVCPICSQ 262
The alignment shows that the ConE6E7 fusion antigen has the same design as that of SEQ ID NO: 20, i.e., the IgE leader – mutated E6 – the endoproteolytic cleavage site – mutated E7, indicating that the E6E7 fusion antigen design used the claimed invention has been used and proven successful at the time of invention.
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 Cassetti, GenBank: ABQ44353.1, GenBank: AEI61551.1 and Yan to arrive at the invention as claimed. One would have been motivated to do so to construct an HPV52 E6E7 fusion antigen based on the design blueprint of ConE6E7 taught in Yan which has been used and proven successful at the time of invention. The resulting fusion antigen would comprise amino acid sequence that is at least 98% or 99% identical to SEQ ID NO: 20.
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 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 10-21 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 2, 4-10, 12, and 16-22 of US 10232030 B2.
Although the conflicting claims are not identical, they are not patentably distinct from each other. The patented claims are related to a fusion HPV52 E6E7 protein comprising at least a fragment of SEQ ID NO:20. The patented claims are directed to a composition that comprises a nucleic acid sequence encoding at least a fragment of SEQ ID NO: 20. Since a peptide sequence is obvious over a nucleic acid sequence encoding it, the instant claims which are directed to an HPV52 E6E7 fusion antigen involving SEQ ID NO: 20 is obvious over that nucleic acid encoding SEQ ID NO: 20 recited in claims 2, 4-10, 12, and 16-22 of US 10232030 B2.
Therefore, claims 10-21 are obvious over claims 2, 4-10, 12, and 16-22 of US 10232030 B2.
(Previous Rejection – Maintained) Claims 10-21 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-20 of US 10905755 B2.
Although the conflicting claims are not identical, they are not patentably distinct from each other. The patented claims are directed to composition comprising a fusion HPV52 E6E7 protein comprising at least a fragment of SEQ ID NO:20. The patented claims are directed to a composition that comprises a nucleic acid sequence encoding at least a fragment of SEQ ID NO: 20.
Since a peptide sequence is obvious over a nucleic acid sequence encoding it, the instant claims which are directed to an HPV52 E6E7 fusion antigen involving SEQ ID NO: 20 is obvious over that nucleic acid encoding SEQ ID NO: 20 recited in claims 1-20 of US 10905755 B2.
Therefore, claims 10-21 are obvious over claims 1-20 of US 10905755 B2.
Response to Applicant’s Arguments
Applicant’s arguments filed on Sep. 26, 2025 have been fully considered. Arguments regarding withdrawn rejections are moot. Applicant’s arguments relevant to the current rejections are addressed as follows.
To the 103 rejection of claims 16 and 17 (now extended to claims 1-15 and 18-21) over Cassetti, GenBank: ABQ44353.1, GenBank: AEI61551.1 and Yan, Applicant argues that Cassetti, GenBank: ABQ44353.1 and GenBank: AEI61551.1 do not teach or disclose HPV52 E6-E7 fusion antigens as claimed, that Yan does not remedy the deficiencies, and that Cassetti, GenBank: ABQ44353.1, GenBank: AEI61551.1 and Yan do not provide a skilled artisan with any predictability or expectation of success in arriving at the HPV52 E6-E7 fusion antigen of the present invention.
Applicant’s arguments are not persuasive. As indicated in the rejection body above, it would have been prima facie obvious to one of ordinary skill in the art at the time of invention to construct an HPV52 E6-E7 fusion antigen by linking the HPV52 E6 and E7 proteins in one fusion antigen based on teachings of Cassetti, GenBank: ABQ44353.1 and GenBank: AEI61551.1. A simple direct fusion construct of HPV52 E6 and E7, about 90% identical to SEQ ID NO: 20, would lack the IgE leader sequence, the endoproteolytic cleavage site, and the mutations abolishing the oncogenic sites. These deficiencies are remedied by Yan, which teaches a HPV16 E6-E7 fusion antigen (ConE6E7) comprising the same IgE leader sequence (underlined), the same endoproteolytic cleavage site (underlined), and mutations abolishing the oncogenic sites of the HPV16 E6 and E7 proteins. One of ordinary skill in the art would have found it obvious to combine the teachings of Cassetti, GenBank: ABQ44353.1, GenBank: AEI61551.1 and Yan to arrive at the invention as claimed. One would have been motivated to do so to construct an HPV52 E6E7 fusion antigen based on the design blueprint of ConE6E7, taught in Yan, which has been used and proven successful at the time of invention. The resulting fusion antigen would comprise amino acid sequence that is at least 98% or 99% identical to SEQ ID NO: 20.
As to applicant’s argument about predictability and expectation of success to arrive at the invention as claimed, both Cassetti and Yan teach the construction of HPV E6-E7 fusion proteins, with Yan teaching an E6-E7 fusion protein for a different HPV type with the same layout of sequence regions as claimed SEQ ID NO: 20 (i.e. the IgE leader – mutated E6 – the endoproteolytic cleavage site – mutated E7). A skilled artisan would have readily predicted the successful construction of a HPV52 E6-E7 fusion antigen as claimed, with the availability of HPV52 E6 and E7 sequences.
To the obviousness double patenting rejections, Applicant requests that the rejections be held in abeyance until the claims are allowed. The rejections are, thus, maintained.
Conclusion
No claims are allowed.
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, JANET ANDRES on (571) 272-0867, 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