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 .
Withdrawn Objections/Rejections
The objection to claim 42 is withdrawn. The amendment to the claims correct the typographical error.
The rejection of claims 43-49, on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,369,669, is withdrawn. A terminal disclaimer was filed to overcome this rejection.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 43-49, as amended or previously presented, is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Tangy (US 9,005,925; pub date:4/14/2015; effectively filed 6/20/2003).
Regarding claim 43, Tangy discloses a Schwarz strain of the measles virus (i.e. a replication competent recombinant virus of the family Paramyxoviridae comprising (i) the nucleotide sequence encoding the full length antigenomic (+)RNA strand of the measles virus Schwarz strain (from position 83 to position 15976 of SEQ ID NO: 82); (ii) a T7 promoter sequence comprising a GGG motif at its 3' end, operably linked to the nucleotide sequence of (i); (iii) a hammerhead ribozyme sequence (from position 29 to position 82 of SEQ ID NO: 82) located adjacent to the GGG motif at one end and adjacent to the nucleotide sequence of (i) at the other end) comprising an expression vector (claim 1). SEQ ID NO:82 has 100% sequence identity with SEQ ID NO:2 of claim 43. As such, Tangy discloses the limitations of claim 43.
Regarding instant claim 44, this claim further specifies the limitations of the fragment of (b), which Tangy does not expressly disclose. However, the fragment of (b) is an alternative embodiment with (a) and (c) and the instant claim 44 does not specify that the claim is limited specifically to the fragment of claim (b). As such, the disclosure of the limitations of (a) by Tangy, as discussed above, meets the limitations of claim 44.
Regarding instant claim 45, SEQ ID NO:82 as disclosed by Tangy has 100% identity with the TRP2 sequence of SEQ ID NO:2. Since SEQ ID NO:2 is the human sequence, inherently the disclosure of SEQ ID NO:82 by Tangy must also be the human sequence because it is identical to SEQ ID NO:2.
Regarding instant claims 46 and 47, Tangy’s disclosures of a measles virus Schwarz strain encompasses the limitations of Morbillivirus (claim 46) and measles virus (claim 47) as claimed.
Regarding claims 48 and 49, Tangy discloses that the measle virus may further comprises a heterologous cDNA sequence encoding an immunogenic amino acid sequence (col 7, starting line 6).
As such, the prior art of Tangy anticipates the claims because it discloses all of the limitations of the claims.
Response to Arguments
Applicant's arguments filed 10/14/2025 have been fully considered but they are not persuasive.
Applicant traverses this rejection and submits that Tangy discloses a Schwartz strain measle virus SEQ ID NO:82 but is completely silent with respect to a virus encoding TRP2 or a variant thereof.
In response, Applicant is not giving the claims their broadest reasonable interpretation. Claims 43 and dependent recite, “a fragment of the tumor antigen TRP2 comprising at least one antigen epitope of TRP2”. The breadth of “a fragment” means that any two or more nucleic acids in common with the sequence encoding with at least one antigen epitope of TRP2. SEQ ID NO:82 of Tangy has at least two nucleic acids in common at least one antigen epitope of TRP2. As such, the great breadth of the claimed fragment is disclosed by Tangy.
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.
Claim(s) 43-49, as amended or previously presented, is/are rejected under 35 U.S.C. 103 as being unpatentable over Tangy (US 9,005,925; pub date:4/14/2015; effectively filed 6/20/2003), as applied to claims 43-49 above, and further in view of Wang (Wang et al. The Journal of Experimental Medicine • Volume 184 December 1996 2207–2216).
Claims 43-49 are taught by Tangy as discussed above. Tangy does not teach the limitations of (b) a fragment of TRP2 comprising at least one antigenic epitope of TRP2, as recites in claim 43. Tangy also does not teach wherein the epitope of TRP2 comprises a sequence from 7 to 15 contiguous amino acids. However, Wang teaches Here we report that TRP-2 was identified as a second tumor antigen recognized by a HLA-A31–restricted CTL clone derived from the TIL586 cell line. The peptide LLPGGRPYR epitope was subsequently identified from the coding region of TRP-2 based on studies of the recognition of truncated TRP-2 cDNAs and the HLA-A31 binding motif. This epitope peptide was capable of sensitizing target cells for lysis by a CTL clone (abstract). Figure 4 on page 2211 discloses the nucleic acid sequence for the epitope.
As such, it would have been obvious to an artisan of ordinary skill before the effective filing date to use the sequence encoding the LLPGGRPYR epitope of TRP2 taught by Wang into the measle virus of Tangy using viral recombinant methods well established in the prior art to predictably arrive at embodiments of (b) in claims 43-49. An artisan would have a reasonable expectation of success because molecular biology method for integrating the epitope sequence of Wang into the measle virus of Tangy were well established in the prior art. Further, the artisan would be motivated to use the epitope sequence of Wang in the measle virus of Tangy because this epitope peptide was capable of sensitizing target cells for lysis by a CTL clone, as taught by Wang. As such, the instant claims are rendered obvious by Tangy in view of Wang.
Response to Arguments
Applicant's arguments filed 10/14/2025 have been fully considered but they are not persuasive.
Applicant traverses this rejection on the grounds that Tangy does not teach the TRP sequence as discussed above. Applicant further submits that Wang does not supplement the deficiencies of Tangy.
In response, Applicant is not giving the claims their broadest reasonable interpretation as discussed above. Further, Tangy does teach the virus as claimed above. Further, Tangy discloses that the measle virus may further comprises a heterologous cDNA sequence encoding an immunogenic amino acid sequence (col 7, starting line 6) as discussed above and also teaches that vector can be used to deliver such immunogenic amino acid sequences. Wang does teach a specific sequence encoding an antigenic epitope of TRP2 which is a species of immunogenic amino acid sequence as Tangy states can be used in their viral vector. Wang also provides motivation to add it to the virus of Tangy (i.e.- this epitope peptide was capable of sensitizing target cells for lysis by a CTL clone). Thus contrary to Applicant’s assertion, Tangy in view of Wang provide sufficient teaching, suggest, and motivation to combine in a predictable manner.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 43-49 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
When determining if a recited genus has adequate written description for a genus:
(1) the broadest reasonable interpretation of the genus is determined;
(2) the disclosure is examined to determine if the specification has provided a representative number of species to describe the complete structure of the genus;
(3) the disclosure is examined to determine whether a representative number of species have been sufficiently described by other relevant characteristics, specified features and functional attributes that would distinguish different members of the claimed genus; and
(4) the state of the art is examined to the determine if it supports/supplement the genus description in the specification in a manner that would demonstrate the application was in possession of the claimed genus at the time of effectively filing.
Claim 43 and thus dependents recite the genus, “a variant of (a) or (b), wherein the variant is 90% identical to the sequence of TRP2 depicted in SEQ ID NO:2”.
Breath of the Genus: The breadth of the claimed “variant” or a variant of a fragment of the TRP2 having 90% identity with the sequence of SEQ ID NO:2 encompasses any contiguous or non-contiguous sequence comprising 90% of its sequence in common with SEQ ID NO: and 10% of its sequence different from SEQ ID NO:2. The different can be in the form of deletion, addition, substitution or a combination thereof. Thus the breadth of the claimed variant is very broad comprising a large number of divergent sequences in structure and potentially function as well.
Specification Description: The only place in the specification that provides an explicit disclosure of the claimed genus is newly added claim 43.
The specification also generically describes the following (citation from Pre-Grant Publication):
[0023] Preferably, the recombinant virus of the family Paramyxoviridae comprises an expressible polynucleotide encoding a variant of a tumor antigen and/or of a fragment of a tumor antigen. As used herein, the term “variant” of a tumor antigen relates to an antigen being non-identical to said tumor antigen having the activity of modulating the immune response. Thus, as used herein, the term polypeptide “variant” relates to any chemical molecule comprising at least one polypeptide or fusion polypeptide as specified elsewhere herein, having the indicated activity, but differing in primary structure from said polypeptide or fusion polypeptide. Thus, the polypeptide variant, preferably, is a mutein having the indicated activity. Preferably, the polypeptide variant comprises a peptide having an amino acid sequence corresponding to an amino acid sequence of 5 to 200, more preferably 6 to 100, even more preferably 7 to 50, or, most preferably, 8 to 30 consecutive amino acids comprised in a polypeptide as specified above. Moreover, also encompassed are further polypeptide variants of the aforementioned polypeptides. Such polypeptide variants have at least essentially the same biological activity as the specific polypeptides. Moreover, it is to be understood that a polypeptide variant as referred to in accordance with the present invention shall have an amino acid sequence which differs due to at least one amino acid substitution, deletion and/or addition, wherein the amino acid sequence of the variant is still, preferably, at least 50%, 60%, 70%, 80%, 85%, 90%, 92%, 95%, 97%, 98%, or 99% identical with the amino acid sequence of the specific polypeptide. The degree of identity between two amino acid sequences can be determined by algorithms well known in the art. Preferably, the degree of identity is to be determined by comparing two optimally aligned sequences over a comparison window, where the fragment of amino acid sequence in the comparison window may comprise additions or deletions (e.g., gaps or overhangs) as compared to the sequence it is compared to for optimal alignment. The percentage is calculated by determining, preferably over the whole length of the polypeptide, the number of positions at which the identical amino acid residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the window of comparison and multiplying the result by 100 to yield the percentage of sequence identity. Optimal alignment of sequences for comparison may be conducted by the local homology algorithm of Smith and Waterman (1981), by the homology alignment algorithm of Needleman and Wunsch (1970), by the search for similarity method of Pearson and Lipman (1988), by computerized implementations of these algorithms (GAP, BESTFIT, BLAST, PASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group (GCG), 575 Science Dr., Madison, Wis.), or by visual inspection. Given that two sequences have been identified for comparison, GAP and BESTFIT are preferably employed to determine their optimal alignment and, thus, the degree of identity. Preferably, the default values of 5.00 for gap weight and 0.30 for gap weight length are used. Polypeptide variants referred to herein may be allelic variants or any other species specific homologs, paralogs, or orthologs; moreover, the polypeptide variants referred to herein include fragments of the specific polypeptides or the aforementioned types of polypeptide variants as long as these fragments and/or variants have the biological activity as referred to above. Further included are variants which differ due to posttranslational modifications such as phosphorylation, glycosylation, ubiquitinylation, sumoylation, or myristylation, by including non-natural amino acids, and/or by being peptidomimetics. Preferably, the variant of the tumor antigen or fragment of a tumor antigen comprises, preferably consists of, at least one of a variant of (i) a HPV E6 polypeptide, preferably of an E6 polypeptide of a high-risk HPV, e.g. of a HPV16 E6 (Genbank Acc No: NP_041325.1 GI:9627104), (ii) a HPV E7 polypeptide, preferably of an E7 polypeptide of a high-risk HPV, e.g. of a HPV16 E7 (Genbank Acc No: NP_041326.1 GI:9627105); (iii) TRP2, preferably human TRP2 (preferably. encoded by Genbank Acc No: NM 001922.4 GI:1015809739), (iv) cancer/testis antigen 1B (CTAG1B, also referred to as NY-ESO, preferably encoded by Genbank Acc No: NM 001327.2 GI:215272337), or (v) an arbitrary combination of any of (i) to (iv).
However, the specification does not provide any species examples of such a variant and only provide the full length of SEQ ID NO:2. As such the specification fails to any description of a representative number of species of variant and thus does not describe the complete structure of the claimed variants.
State of the Art: A search of SEQ ID NO:2 also failed to provide any examples of sequence variants with 90% identity with SEQ ID NO:2. The closest sequences found were Acession No. DQ902581.1 which is a homo sapien TRP2 isoform variant comprising 99% identity with SEQ ID NO:2, having a deletion between aa 364 and 365 (Khong and Rosenberg. J Immunol 2002 168(2):951-956). However, a great deal more changes are encompassed by 90% to the SEQ ID NO:2 sequence that the prior art does not describe. Further, any changes made, even a little as one amino acid can lead to a structurally different amino acid sequence with a different function. As such, art teaches making variants of an amino acid sequence is unpredictable.
The claimed genus “variant” lack written description because the specification fails to provide adequate description of a representative number of species to disclose the complete structure of the genus by other relevant characteristics, specified features and functional attributes that would distinguish different members. The art at the time of effective filing also description of any sequences fitting the description of such claimed variant to supplement the shortcoming of the disclosure. As such, an artisan of ordinary skill would come to the conclusion that the application was in possession of the claimed genus at the time of effectively filing.
Response to Arguments
Applicant's arguments filed 10/14/2025 have been fully considered but they are not persuasive.
Applicant submits that amending claim 43 to recites “at least” 90% identical to the sequence of TRP2 depicted in SEQ ID NO:2. A person of ordinary skill in the art, who would have had access to predictive tools for designing hTRP3 variants that have hTRP2 biological activity would not have required more specific guidance to conclude that the inventors had possession of the claimed invention.
In response, Applicant is not considered the great breadth of the claimed sequences and the unpredictability of altering a sequence and retaining its structural properties. The breadth of the claimed polynucleotide encoding at least one of (a), (b), and (c), broadly encompasses any two or more nucleic acids in common with TRP2 epitope up to any sequence encoding TRP2 and sequences with 100% identity to TRP2. This is an enormous number of species that are structurally and functionally diverse in nature. Examiner agrees that the art provides computational tools to predict alterations and fragments of TRP2 as candidates for variants of TRP2. However, the art teaches, even with such tools, altering amino acid sequence structures can alter secondary and tertiary structure in a manner that has unknown consequence on the end product function. As such, absent a description in the specification and prior art of sequence variants and fragments that are know to retain the functional properties by a representative number of species to describe the complete structure of the genus, one of skill cannot envision the species of the genus of TRP2 variants and fragments that retain the function described in the specification and art. As such, one of skill would not conclude Applicant was in possession of such a large and diverse gene of TRP2 fragments and variants as Applicant asserts.
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCIA STEPHENS NOBLE whose telephone number is (571)272-5545. The examiner can normally be reached M-F 9-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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MARCIA S. NOBLE
Primary Examiner
Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632