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 .
Claims 1 and 2 have been amended. Claims 3-7 have been added. Claims 1-7 are pending and under consideration.
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 3-7 are rejected and claims 1 and 2 remain 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.
95% homologues
Claim 1 is reliant in part on a genus of functional variants that suppress tumor growth having at least 95% homology to SEQ ID NO:3 in the method of treating cancer. When given the broadest reasonable interpretation, the requirement for 95% homology to SEQ ID NO: 3 allows for substitutions, insertions and deletions at any position within SEQID NO: 3. The specification fails to teach a minimal sequence within SEQ ID NO:3 which is required for suppression of tumor growth, such that one of skill in the art can envisage members of the genus of variants effective for the treatment of cancer. The specification fails to describe a representative number of peptides having 95% homology to SEQ ID NO: 3 sufficient to describe the claimed genus, because the specification fails to describe any other member other than SEQ ID NO:3. This rejection applies to a fused protein, complexes of p50 and expression vectors comprising nucleic acid sequence encoding the functional variant and encoding the fusion protein of the functional variants as well. One of skill in the art would reasonably conclude that applicant was not in possession of the peptides having 95% homology to SEQ ID NO:3 and activity against cancer at the time of filing.
Applicant argues that the specification provides detailed structural “definitions”, broad but definite homology ranges and concrete embodiments demonstrating possession and enablement of the full genus. Applicant argues that paragraph [00114] discloses that functional equivalent molecules may be used including peptidomimetics, stapled peptide, retro-inverso peptides or amino acid derivative peptides and in paragraph [00132]-[00135] which states that amino acid derivatives, non-natural amino acids, chemically modified side chains, peptide backbone modification, D-amino acids and peptidomimetics are all within the scope of the inventio; and further within paragraph s [00165]-[00172]) which contemplate fusion of KPC1 or p50 sequences to immunoglobulin constant domains and provide methods for producing the fusion proteins. This has been considered but not found persuasive. The claimed genus encompasses 95% variants having a defined activity of suppressing tumor growth. It is noted that “KPC1” is not part of the genus of variants of p50. These generic types of peptides, modified peptides and peptiomimetics, which are not peptides, fail to provide a representative number of peptides sufficient to describe the required genus of 95% variants having a defined activity of suppressing tumor growth. Applicant argues that paragraph [00130] explicitly defines permissible homolog of the disclosed SEQ ID NO: 3 and 4 with percent identities ranging from about 50% to about 97% or more. This has been considered but not found persuasive. Firstly, SEQ ID NO: 4 is the amino acid sequence of KPC1, not p50. A disclosure of a KPC1 sequence fails to describe the genus of variant p50 sequences encompassed by the claims. Secondly, a contemplation of variants in term of percent identities fail to provide a representative number of peptides sufficient to describe the required genus of 95% variants having a defined activity of suppressing tumor growth and fails to correlate a defined structural element with the activity of suppressing tumor growth.
Applicant concludes that the specification provides a concrete “seed” sequence, defines explicitly homology thresholds and describes broad but chemically and structurally diver set of variants and thus meets the requirements of disclosing a representative number of species or otherwise “shows a clear structure-function correlation” such that a person of ordinary skill in the art would recognize that the inventor was in possession of the broad genus of peptides a the time of filing. This is not persuasive for the reason set forth above.
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.
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.
The rejection of claims 1 and 2 under 35 U.S.C. 102(a)(1) as being anticipated by Russell et al (US 2007/0071771) as evidenced by Bolt et al (The Journal of General Virology, 2002, Vol. 83, pp. 1157-1165) is withdrawn in light of applicant’s amendment requiring that the agent which upregulates p50 is KPC1 or a KPC2 siRNA.
Claims 3, 4 and 6 are rejected and claims 1 and 2 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bancel et al (WO2013/151672). Please note: an abridged version of ‘672 is being provided with the Office action due to the jumbo size of the original document.
Bancel et al disclose a method of treating cancer in a subject comprising administering an oncology related polypeptide to a subject (claims 1-7 of ‘672). Bancel et al teach that an oncology-related polypeptide of interest includes SEQ ID NO: 7434 and 7435 (claim 16(a)).
Query Length: 434; Sequence Length: 969;
Score: 2960 (468.7 bits), 99.6% of highest possible score 2972;
Expect value: 9.234e-130;
Identities: 434 / 434 (100.0%); Positives: 434 / 434 (100.0%);
Query Identity: 100.0%; Query Coverage: 100.0%;
Subject Identity: 44.8%; Subject Coverage: 44.8%;
Alignment Length: 434;
Q: 1 MAEDDPYLGRPEQMFHLDPSLTHTIFNPEVFQPQMALPTADGPYLQILEQPKQRGFRFRY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S: 1 MAEDDPYLGRPEQMFHLDPSLTHTIFNPEVFQPQMALPTADGPYLQILEQPKQRGFRFRY 60
Q: 61 VCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHCE 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S: 61 VCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHCE 120
Q: 121 DGICTVTAGPKDMVVGFANLGILHVTKKKVFETLEARMTEACIRGYNPGLLVHPDLAYLQ 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S: 121 DGICTVTAGPKDMVVGFANLGILHVTKKKVFETLEARMTEACIRGYNPGLLVHPDLAYLQ 180
Q: 181 AEGGGDRQLGDREKELIRQAALQQTKEMDLSVVRLMFTAFLPDSTGSFTRRLEPVVSDAI 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S: 181 AEGGGDRQLGDREKELIRQAALQQTKEMDLSVVRLMFTAFLPDSTGSFTRRLEPVVSDAI 240
Q: 241 YDSKAPNASNLKIVRMDRTAGCVTGGEEIYLLCDKVQKDDIQIRFYEEEENGGVWEGFGD 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S: 241 YDSKAPNASNLKIVRMDRTAGCVTGGEEIYLLCDKVQKDDIQIRFYEEEENGGVWEGFGD 300
Q: 301 FSPTDVHRQFAIVFKTPKYKDINITKPASVFVQLRRKSDLETSEPKPFLYYPEIKDKEEV 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S: 301 FSPTDVHRQFAIVFKTPKYKDINITKPASVFVQLRRKSDLETSEPKPFLYYPEIKDKEEV 360
Q: 361 QRKRQKL-PNFSDSFGGGSGAGAGGGGMFGSGGGGGGTGSTGPGYSFPHYGFPTYGGITF 419
||||||| ||||||||||||||||||||||||||||||||||||||||||||||||||||
S: 361 QRKRQKLMPNFSDSFGGGSGAGAGGGGMFGSGGGGGGTGSTGPGYSFPHYGFPTYGGITF 420
Q: 420 HPGTTKSNAGMKHGT 434
|||||||||||||||
S: 421 HPGTTKSNAGMKHGT 435
FS PROTEIN; PS
MTY protein
PSL SEQ ID NO 7435
SEQN 7435
ALIGN
Query Length: 434; Sequence Length: 968;
Score: 2943 (504.1 bits), 99.0% of highest possible score 2972;
Expect value: 2.037e-140;
Identities: 433 / 433 (100.0%); Positives: 433 / 433 (100.0%);
Query Identity: 99.8%; Query Coverage: 99.8%;
Subject Identity: 44.7%; Subject Coverage: 44.7%;
Alignment Length: 433;
Q: 1 MAEDDPYLGRPEQMFHLDPSLTHTIFNPEVFQPQMALPTADGPYLQILEQPKQRGFRFRY 60
||||||||||||||||||||||||||||||||||||||| ||||||||||||||||||||
S: 1 MAEDDPYLGRPEQMFHLDPSLTHTIFNPEVFQPQMALPT-DGPYLQILEQPKQRGFRFRY 59
Q: 61 VCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHCE 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S: 60 VCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHCE 119
Q: 121 DGICTVTAGPKDMVVGFANLGILHVTKKKVFETLEARMTEACIRGYNPGLLVHPDLAYLQ 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S: 120 DGICTVTAGPKDMVVGFANLGILHVTKKKVFETLEARMTEACIRGYNPGLLVHPDLAYLQ 179
Q: 181 AEGGGDRQLGDREKELIRQAALQQTKEMDLSVVRLMFTAFLPDSTGSFTRRLEPVVSDAI 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S: 180 AEGGGDRQLGDREKELIRQAALQQTKEMDLSVVRLMFTAFLPDSTGSFTRRLEPVVSDAI 239
Q: 241 YDSKAPNASNLKIVRMDRTAGCVTGGEEIYLLCDKVQKDDIQIRFYEEEENGGVWEGFGD 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S: 240 YDSKAPNASNLKIVRMDRTAGCVTGGEEIYLLCDKVQKDDIQIRFYEEEENGGVWEGFGD 299
Q: 301 FSPTDVHRQFAIVFKTPKYKDINITKPASVFVQLRRKSDLETSEPKPFLYYPEIKDKEEV 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S: 300 FSPTDVHRQFAIVFKTPKYKDINITKPASVFVQLRRKSDLETSEPKPFLYYPEIKDKEEV 359
Q: 361 QRKRQKL-PNFSDSFGGGSGAGAGGGGMFGSGGGGGGTGSTGPGYSFPHYGFPTYGGITF 419
||||||| ||||||||||||||||||||||||||||||||||||||||||||||||||||
S: 360 QRKRQKLMPNFSDSFGGGSGAGAGGGGMFGSGGGGGGTGSTGPGYSFPHYGFPTYGGITF 419
Q: 420 HPGTTKSNAGMKHGT 434
|||||||||||||||
S: 420 HPGTTKSNAGMKHGT 434
SEQ ID NO: 7434 and 7435 of Bancel et al meet the limitations of a method of treating cancer comprising administering to a subject a peptide which is at least 70% homologous to SEQ ID NO: 3. Bancel et al disclose that the oncology-related polypeptides include single molecules or a multi-molecular complexes (paragraph [00060]), which meet the limitations of a complex comprising a peptide which is at least 95% homologous to the p50 sequence of SEQ ID NO:3. Bancel et al disclose the oncology-related polypeptides include fusion proteins (paragraph [000563]), wherein the fusion proteins include human serum albumin (paragraph [000564]) which meet the limitations of a fusion protein comprising a peptide which is at least 95% homologous to the p50 sequence of SEQ ID NO:3 in claims 1, 3, 4 and 6.
Bancel et al disclose that the tumor growth results from, in part, breast cancer or osteosarcoma (claim 5 of ‘672) which meets the same limitations in claim 2.
Applicant argues that the rejection is incorrect because SEQ ID NO: 7434 and SEQ ID NO: 7435 have 968 and 969 amino acids, respectively whereas the instant SEQ ID NO: 3 is only 434 amino acids and that because the prior art protein as are nearly double in size of the instant proteins, the limitation cannot be met. This has been considered but not found persuasive. Claims 1-4 and 6 are drawn to a method of treating cancer in a subject comprising administering to said subject a therapeutically effective amount of a peptide comprising functional variant of p50 that suppresses tumor growth, wherein the variant has at least about 95% homology to SEQ ID NO:3. SEQ ID NO: 7434 and 7435 comprise a functional variant of SEQ ID NO: 3 at residues 1-435 and 1-434 of SEQ ID NO: 7434 and 7435 having 95% homology to SEQ ID NO: 3. Applicant argues that there are no teachings in Bancel regarding truncating SEQ ID NO: 7434 or 7435 to 434 residues. This has been considered but not found persuasive. Given the plain language of the claim, “a peptide comprising p50 or a functional variant thereof” , wherein the variant is “at least about 95% homologous to the p50 sequence as set forth as SEQ ID NO:3” , Bancel anticipates the instant claims.
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4, 6 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Bancel et al (WO2013/151672).
Bancel teach the administration of the oncology-related polynucleotides of the invention to a subject to reduce and/or ameliorating at least one symptom of cancer in a subject need thereof (claim 2 of ‘672). Bancel et al disclose a "primary construct" or "primary mRNA construct" which is an oncology-related polynucleotide transcript which encodes one or more oncology-related polypeptides of the invention and which retains sufficient structural and/or chemical features to allow the oncology-related polypeptide of interest encoded therein to be translated (paragraph [0036]). Bancel et al disclose the oncology-related primary construct as cyclized, or concatemerized, generating a translation competent molecule to assist interactions between poly-A binding proteins and 5 '-end binding proteins which meets the limitation of an expression vector in claim 7.
Bancel et al do not specifically teach that the cyclized primary construct is administered to the subject in a method of reducing and/or ameliorating at least one symptom of cancer in said subject. Bancel et al teach that lipidoid complexes of oncology-related polynucleotides, primary constructs, or mmRNA can be administered by various means including, but not limited to, intravenous, intramuscular, or subcutaneous routes. (paragraph [000443]). Thus, one of skill in the art would reasonably conclude that the cyclized, translation competent primary construct can be administered to a subject in need thereof as a lipidoid complex to deliver the oncology-related polynucleotide of the invention in the method of claims 1 and 2 of Bancel et al. One of skill in the art would be motivated to do so because a cyclized vector will provide mRNA in vivo and has the advantage of not being susceptible to contaminating RNAses during isolations which would degrade the mRNA of SEQ ID NO: 7434 and 7435.
The rejection of claims 1 and 2 on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No.11,452,759 is withdrawn in light of applicant’s Terminal Disclaimer.
All other rejections and/or objections as set forth in the previous Office action are withdrawn.
Conclusion
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 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 KAREN A CANELLA whose telephone number is (571)272-0828. The examiner can normally be reached M-F 10-6:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643