DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This office action is in response to an amendment filed 3/16/2026.
Claims 1, 2, 6, 7, 10, 15, 18, 20, 25, 27-29, 32, 33, 36, 37 and 39-42 are pending. Claims 25, 27, 28, 36 and 37 are withdrawn as directed to non-elected subject matter. Therefore, claims 1, 2, 6, 7, 10, 15, 18, 20, 29, 32, 33 and 39-42 are under examination. The election was made without traverse.
The instant application is a 371 filing of PCT//US2020/056890 filed 11/22/2020 which claims priority to provisional application U.S. 62/924,567 filed 10/22/2019.
Information Disclosure Statement
An information disclosure statement filed 3/16/2026 has been identified and the documents considered. The corresponding signed and initialed PTO Form 1449 has been mailed with this action.
Response to Amendments
Applicant's amendment is sufficient to overcome the objection to the claims. As well, the claims under 35 USC 101 have been overcome. It is noted that the amendment has inserted that the sequence is the sequence of SEQ ID NO:2 in place of the 3’ UTR previously recited as SEQ ID NO:3. This is either a mistype or an amendment without correct markings. The claims will be examined and the interpretation as to the claim meaning indicated in each rejection. The purpose of this is for compact prosecution.
Claim Rejections - 35 USC § 112, first paragraph
The following is a quotation of the first paragraph of 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 1, 6, 7, 1015, 18, 20, 29, 32, 33, 39 and 41 are rejected under 35 U.S.C. 112, 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(s), at the time the application was filed, had possession of the claimed invention. This rejection is necessitated by the recitation that the 3’ UTR comprises the sequence of SEQ ID NO:2.
Claim 1 has been amended to recite that the 3’UTR comprises the sequence of SEQ ID NO:2. The previous recitation was SEQ ID NO:3. However, the disclosure does not teach a 3’ UTR that has the sequence of SEQ ID NO:2. The MPEP teaches, “New or amended claims which introduce elements or limitations which are not supported by the as-filed disclosure violate the written description requirement. See, e.g., In re Lukach, 442 F.2d 967, 169 USPQ 795 (CCPA 1971) (subgenus range was not supported by generic disclosure and specific example within the subgenus range); In re Smith, 458 F.2d 1389, 1395, 173 USPQ 679, 683 (CCPA 1972) (a subgenus is not necessarily described by a genus encompassing it and a species upon which it reads). (see e.g. MPEP 2105). Because the disclosure does not teach a 3’ UTR comprising the sequence of SEQ ID NO:2, one cannot conclude that applicant was in possession of the claimed sequence.
Claim Rejections - 35 USC § 103
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.
Claims 1, 2, 6, 7, 10, 15, 18, 29, 32, 33, 39 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al (WO 2019104152) in view of Monahan et al (US 20160206750). This rejection is based upon an understanding that the 3’ UTR is as provided for in the disclosure SEQ ID NO:3. It is newly presented but based in similar references as previously set forth. But, due to the incorporation of claim 3 into the base claims provided in relation to the new limitations. The Zhou reference above is not the same as previously provided.
Zhou et al teach a construct encoding OTC (see abstract) with a polyA tail that is between 50-150 (¶ 0119) wherein the upper limit meets and exceeds the limitations of the instant claims.
[0363] Unique poly-A tail lengths provide certain advantages to the polynucleotides of the present invention. Generally, the length of a poly-A tail, when present, is greater than 30 nucleotides in length. In another embodiment, the poly-A tail is greater than 35 nucleotides in length (e.g., at least or greater than about 35, 40, 45, 50, 55, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1,000, 1,100, 1,200, 1,300, 1,400, 1,500, 1,600, 1,700, 1,800, 1,900, 2,000, 2,500, and 3,000 nucleotides).
The construct further comprise a 5’ UTR and a 3’ UTR wherein the 5’ UTR as recited (SEQ ID NO:2) is taught by Zhou (¶0015-0017). The comparison with Zhou is shown below.
RESULT 1 (SEQ ID NO:2 rnpm)
PCT-US18-62226-196
(NOTE: this sequence has 45 duplicates in the database searched.
See complete list at the end of this report)
Sequence 196, PC/TUS1862226
GENERAL INFORMATION
APPLICANT: MODERNATX, INC.
TITLE OF INVENTION: POLYNUCLEOTIDES ENCODING ORNITHINE TRANSCARBAMYLASE
TITLE OF INVENTION: FOR THE TREATMENT OF UREA CYCLE DISORDERS
FILE REFERENCE: 45817-0021WO1
CURRENT APPLICATION NUMBER: PCT/US18,62226
CURRENT FILING DATE: 2018-11-21
PRIOR APPLICATION NUMBER: PCT/US2018/062226
PRIOR FILING DATE: 2018-11-21
PRIOR APPLICATION NUMBER: 62/765,354
PRIOR FILING DATE: 2018-08-20
PRIOR APPLICATION NUMBER: 62/590,157
PRIOR FILING DATE: 2017-11-22
NUMBER OF SEQ ID NOS: 226
SEQ ID NO 196
LENGTH: 47
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
NAME/KEY: source
OTHER INFORMATION: /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
Query Match 100.0%; Score 47; Length 47;
Best Local Similarity 100.0%;
Matches 47; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAGAGCCACC 47
|||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAGAGCCACC 47.
Monahan teaches the same functional construct and provides both the recited sequence of OTC found in SEQ ID NO:1 (also found in claim 7, 100% related as shown below with SEQ ID NO:111) and the 3’ UTR found in SEQ ID NO:3 (100% related to SEQ ID NO:114).
RESULT 1
US-14-908-351-114
(NOTE: this sequence has 4 duplicates in the database searched.
See complete list at the end of this report)
Sequence 114, US/14908351
Patent No. 9867885
GENERAL INFORMATION
APPLICANT: PhaseRx, Inc.
TITLE OF INVENTION: BLOCK COPOLYMERS
FILE REFERENCE: 3800.PCT1
CURRENT APPLICATION NUMBER: US/14/908,351
CURRENT FILING DATE: 2016-01-28
NUMBER OF SEQ ID NOS: 122
SEQ ID NO 114
LENGTH: 1221
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: mRNA encoding human ornithine transcarbamylase, codon-optimized
for human expression
Query Match 100.0%; Score 1065; Length 1221;
Best Local Similarity 100.0%;
Matches 1065; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AUGCUGUUUAACCUGAGGAUUCUGCUGAACAACGCUGCUUUUCGGAACGGCCACAACUUU 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 48 AUGCUGUUUAACCUGAGGAUUCUGCUGAACAACGCUGCUUUUCGGAACGGCCACAACUUU 107
Qy 61 AUGGUGCGGAACUUUCGGUGCGGACAGCCACUGCAGAACAAAGUGCAGCUGAAGGGGAGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 108 AUGGUGCGGAACUUUCGGUGCGGACAGCCACUGCAGAACAAAGUGCAGCUGAAGGGGAGG 167
Qy 121 GACCUGCUGACCCUGAAAAAUUUCACAGGAGAGGAAAUCAAGUACAUGCUGUGGCUGUCU 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 168 GACCUGCUGACCCUGAAAAAUUUCACAGGAGAGGAAAUCAAGUACAUGCUGUGGCUGUCU 227
Qy 181 GCCGAUCUGAAGUUCCGGAUCAAGCAGAAGGGCGAAUAUCUGCCACUGCUGCAGGGCAAA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 228 GCCGAUCUGAAGUUCCGGAUCAAGCAGAAGGGCGAAUAUCUGCCACUGCUGCAGGGCAAA 287
Qy 241 AGUCUGGGGAUGAUCUUCGAAAAGAGGAGUACUCGGACCAGACUGUCAACAGAGACUGGA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 288 AGUCUGGGGAUGAUCUUCGAAAAGAGGAGUACUCGGACCAGACUGUCAACAGAGACUGGA 347
Qy 301 UUCGCUCUGCUGGGAGGACACCCAUGCUUUCUGACCACACAGGACAUUCAUCUGGGCGUG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 348 UUCGCUCUGCUGGGAGGACACCCAUGCUUUCUGACCACACAGGACAUUCAUCUGGGCGUG 407
Qy 361 AACGAGUCACUGACCGACACAGCUCGAGUCCUGAGCUCCAUGGCAGAUGCCGUGCUGGCA 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 408 AACGAGUCACUGACCGACACAGCUCGAGUCCUGAGCUCCAUGGCAGAUGCCGUGCUGGCA 467
Qy 421 CGGGUCUACAAACAGAGCGACCUGGAUACCCUGGCUAAGGAAGCAAGCAUCCCCAUCAUU 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 468 CGGGUCUACAAACAGAGCGACCUGGAUACCCUGGCUAAGGAAGCAAGCAUCCCCAUCAUU 527
Qy 481 AAUGGGCUGUCCGACCUGUAUCACCCUAUCCAGAUUCUGGCCGAUUACCUGACCCUGCAG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 528 AAUGGGCUGUCCGACCUGUAUCACCCUAUCCAGAUUCUGGCCGAUUACCUGACCCUGCAG 587
Qy 541 GAGCAUUAUUCUAGUCUGAAAGGCCUGACACUGAGCUGGAUUGGGGACGGAAACAAUAUC 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 588 GAGCAUUAUUCUAGUCUGAAAGGCCUGACACUGAGCUGGAUUGGGGACGGAAACAAUAUC 647
Qy 601 CUGCACUCCAUUAUGAUGUCUGCCGCUAAGUUUGGAAUGCAUCUGCAGGCAGCCACACCA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 648 CUGCACUCCAUUAUGAUGUCUGCCGCUAAGUUUGGAAUGCAUCUGCAGGCAGCCACACCA 707
Qy 661 AAAGGCUACGAACCCGAUGCCAGUGUGACUAAGCUGGCCGAACAGUAUGCUAAAGAGAAC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 708 AAAGGCUACGAACCCGAUGCCAGUGUGACUAAGCUGGCCGAACAGUAUGCUAAAGAGAAC 767
Qy 721 GGCACUAAGCUGCUGCUGACCAAUGACCCUCUGGAGGCUGCACACGGAGGCAACGUCCUG 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 768 GGCACUAAGCUGCUGCUGACCAAUGACCCUCUGGAGGCUGCACACGGAGGCAACGUCCUG 827
Qy 781 AUCACUGAUACCUGGAUUUCCAUGGGCCAGGAGGAAGAGAAGAAAAAGCGCCUGCAGGCA 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 828 AUCACUGAUACCUGGAUUUCCAUGGGCCAGGAGGAAGAGAAGAAAAAGCGCCUGCAGGCA 887
Qy 841 UUCCAGGGGUACCAGGUGACAAUGAAAACUGCCAAGGUCGCCGCUUCUGAUUGGACUUUU 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 888 UUCCAGGGGUACCAGGUGACAAUGAAAACUGCCAAGGUCGCCGCUUCUGAUUGGACUUUU 947
Qy 901 CUGCAUUGUCUGCCCCGAAAACCUGAAGAGGUGGACGAUGAGGUCUUCUAUUCACCUAGG 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 948 CUGCAUUGUCUGCCCCGAAAACCUGAAGAGGUGGACGAUGAGGUCUUCUAUUCACCUAGG 1007
Qy 961 AGCCUGGUGUUUCCAGAAGCCGAGAAUCGCAAGUGGACAAUCAUGGCUGUGAUGGUGUCC 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1008 AGCCUGGUGUUUCCAGAAGCCGAGAAUCGCAAGUGGACAAUCAUGGCUGUGAUGGUGUCC 1067
Qy 1021 CUGCUGACUGAUUAUUCCCCCCAGCUGCAGAAACCUAAGUUCUGA 1065
|||||||||||||||||||||||||||||||||||||||||||||
Db 1068 CUGCUGACUGAUUAUUCCCCCCAGCUGCAGAAACCUAAGUUCUGA 1112
Monahan et al also teach that the 3’ UTR associated with this sequence in copending SEQ ID NO:111 is 100% identical to SEQ IS NO:3.
RESULT 7
US-14-908-351-111
(NOTE: this sequence has 4 duplicates in the database searched)
Sequence 111, US/14908351
Patent No. 9867885
GENERAL INFORMATION
APPLICANT: PhaseRx, Inc.
TITLE OF INVENTION: BLOCK COPOLYMERS
FILE REFERENCE: 3800.PCT1
CURRENT APPLICATION NUMBER: US/14/908,351
CURRENT FILING DATE: 2016-01-28
NUMBER OF SEQ ID NOS: 122
SEQ ID NO 111
LENGTH: 1262
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: cDNA encoding human ornithine transcarbamylase, codon-optimized
for human expression
FEATURE:
NAME/KEY: promoter
LOCATION: (1)..(20)
OTHER INFORMATION: T7 promoter
Query Match 100.0%; Score 114; Length 1262;
Best Local Similarity 68.4%;
Matches 78; Conservative 36; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GCGGCCGCUUAAUUAAGCUGCCUUCUGCGGGGCUUGCCUUCUGGCCAUGCCCUUCUUCUC 60
||||||||::||::||||:|||::|:|||||||::|||::|:|||||:||||::|::|:|
Db 1130 GCGGCCGCTTAATTAAGCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTTCTTCTC 1189
Qy 61 UCCCUUGCACCUGUACCUCUUGGUCUUUGAAUAAAGCCUGAGUAGGAAGUCUAG 114
:|||::|||||:|:|||:|::||:|:::|||:||||||:|||:||||||:|:||
Db 1190 TCCCTTGCACCTGTACCTCTTGGTCTTTGAATAAAGCCTGAGTAGGAAGTCTAG 1243
Based on such teachings, it would have prima facie been obvious to one of ordinary skill in the art at the time the invention was made to use known sequence in similar constructs in related constructs. Such a modification would have resulted in a method encompassed by claim 1. In this case both Zhou and Monahan teach a mRNA encoding OTC with a 5’ UTR and a 3’ UTR and a polyA sequence. The specifics as recited were well known in the art. Specifically, a construct as recited in claim 1 is taught
comprising a 5’ UTR of SEQ ID NO:2 is shown by Zhou et al
an mRNA sequence with an ORF encoding OTC with at least 95% identity to SEQ ID NO:1 is shown by Monahan
comprising a 3’ UTR of SEQ ID NO:3 if the claim intended that as shown above but is shown by Monahan et al
Zhou teaches a long polyA tail that is at least 150 nucleotides. The claims require one of 150-1000 nucleotides and claim 39 and 40 has 150-800 both encompassed by Zhou
Thus, a person of ordinary skill in the art, absent evidence to the contrary, would have reasonably expected that the known sequences would allow one to use them interchangeably in related sequences.
As recited in claim 6, the sequence of Monahan meets that of SEQ ID NO:7. Below, top is SEQ ID NO:7 and the bottom sequence is the translation of Monahan.
Range 1: 1 to 354GraphicsNext MatchPrevious Match
Alignment statistics for match #1
Score
Expect
Method
Identities
Positives
Gaps
738 bits(1904)
0.0
Compositional matrix adjust.
354/354(100%)
354/354(100%)
0/354(0%)
Query 1 MLFNLRILLNNAAFRNGHNFMVRNFRCGQPLQNKVQLKGRDLLTLKNFTGEEIKYMLWLS 60
MLFNLRILLNNAAFRNGHNFMVRNFRCGQPLQNKVQLKGRDLLTLKNFTGEEIKYMLWLS
Sbjct 1 MLFNLRILLNNAAFRNGHNFMVRNFRCGQPLQNKVQLKGRDLLTLKNFTGEEIKYMLWLS 60
Query 61 ADLKFRIKQKGEYLPLLQGKSLGMIFEKRSTRTRLSTETGFALLGGHPCFLTTQDIHLGV 120
ADLKFRIKQKGEYLPLLQGKSLGMIFEKRSTRTRLSTETGFALLGGHPCFLTTQDIHLGV
Sbjct 61 ADLKFRIKQKGEYLPLLQGKSLGMIFEKRSTRTRLSTETGFALLGGHPCFLTTQDIHLGV 120
Query 121 NESLTDTARVLSSMADAVLARVYKQSDLDTLAKEASIPIINGLSDLYHPIQILADYLTLQ 180
NESLTDTARVLSSMADAVLARVYKQSDLDTLAKEASIPIINGLSDLYHPIQILADYLTLQ
Sbjct 121 NESLTDTARVLSSMADAVLARVYKQSDLDTLAKEASIPIINGLSDLYHPIQILADYLTLQ 180
Query 181 EHYSSLKGLTLSWIGDGNNILHSIMMSAAKFGMHLQAATPKGYEPDASVTKLAEQYAKEN 240
EHYSSLKGLTLSWIGDGNNILHSIMMSAAKFGMHLQAATPKGYEPDASVTKLAEQYAKEN
Sbjct 181 EHYSSLKGLTLSWIGDGNNILHSIMMSAAKFGMHLQAATPKGYEPDASVTKLAEQYAKEN 240
Query 241 GTKLLLTNDPLEAAHGGNVLITDTWISMGQEEEKKKRLQAFQGYQVTMKTAKVAASDWTF 300
GTKLLLTNDPLEAAHGGNVLITDTWISMGQEEEKKKRLQAFQGYQVTMKTAKVAASDWTF
Sbjct 241 GTKLLLTNDPLEAAHGGNVLITDTWISMGQEEEKKKRLQAFQGYQVTMKTAKVAASDWTF 300
Query 301 LHCLPRKPEEVDDEVFYSPRSLVFPEAENRKWTIMAVMVSLLTDYSPQLQKPKF 354
LHCLPRKPEEVDDEVFYSPRSLVFPEAENRKWTIMAVMVSLLTDYSPQLQKPKF
Sbjct 301 LHCLPRKPEEVDDEVFYSPRSLVFPEAENRKWTIMAVMVSLLTDYSPQLQKPKF 354
As recited in claim 10, Zhou teaches a 5’ cap (see ¶0045) and uridine (see ¶0195). The sequence is part of a LNP (see e.g. ¶0087).
Claim 2 recites in the instant sequence SEQ ID NO:4 which has a nucleotide that is in addition to that of Monahan. This sequence is found in SEQ ID NO:111 and the correlation is shown below.
RESULT 1
US-14-908-351-111
(NOTE: this sequence has 4 duplicates in the database searched.
See complete list at the end of this report)
Sequence 111, US/14908351
Patent No. 9867885
GENERAL INFORMATION
APPLICANT: PhaseRx, Inc.
TITLE OF INVENTION: BLOCK COPOLYMERS
FILE REFERENCE: 3800.PCT1
CURRENT APPLICATION NUMBER: US/14/908,351
CURRENT FILING DATE: 2016-01-28
NUMBER OF SEQ ID NOS: 122
SEQ ID NO 111
LENGTH: 1262
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: cDNA encoding human ornithine transcarbamylase, codon-optimized
for human expression
FEATURE:
NAME/KEY: promoter
LOCATION: (1)..(20)
OTHER INFORMATION: T7 promoter
Query Match 99.9%; Score 1225; Length 1262;
Best Local Similarity 78.3%;
Matches 959; Conservative 266; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAGAGCCACCAUGCUGUUUAACCU 61
|||||:|||||||||||||||||:|||||||||:|:|||||||||||:||:|:::||||:
Db 19 GGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCTGTTTAACCT 78
Qy 62 GAGGAUUCUGCUGAACAACGCUGCUUUUCGGAACGGCCACAACUUUAUGGUGCGGAACUU 121
|||||::|:||:|||||||||:||::::|||||||||||||||:::|:||:|||||||::
Db 79 GAGGATTCTGCTGAACAACGCTGCTTTTCGGAACGGCCACAACTTTATGGTGCGGAACTT 138
Qy 122 UCGGUGCGGACAGCCACUGCAGAACAAAGUGCAGCUGAAGGGGAGGGACCUGCUGACCCU 181
:|||:||||||||||||:|||||||||||:|||||:||||||||||||||:||:|||||:
Db 139 TCGGTGCGGACAGCCACTGCAGAACAAAGTGCAGCTGAAGGGGAGGGACCTGCTGACCCT 198
Qy 182 GAAAAAUUUCACAGGAGAGGAAAUCAAGUACAUGCUGUGGCUGUCUGCCGAUCUGAAGUU 241
||||||:::||||||||||||||:||||:|||:||:|:|||:|:|:|||||:|:||||::
Db 199 GAAAAATTTCACAGGAGAGGAAATCAAGTACATGCTGTGGCTGTCTGCCGATCTGAAGTT 258
Qy 242 CCGGAUCAAGCAGAAGGGCGAAUAUCUGCCACUGCUGCAGGGCAAAAGUCUGGGGAUGAU 301
|||||:||||||||||||||||:|:|:|||||:||:||||||||||||:|:|||||:||:
Db 259 CCGGATCAAGCAGAAGGGCGAATATCTGCCACTGCTGCAGGGCAAAAGTCTGGGGATGAT 318
Qy 302 CUUCGAAAAGAGGAGUACUCGGACCAGACUGUCAACAGAGACUGGAUUCGCUCUGCUGGG 361
|::||||||||||||:||:||||||||||:|:||||||||||:|||::|||:|:||:|||
Db 319 CTTCGAAAAGAGGAGTACTCGGACCAGACTGTCAACAGAGACTGGATTCGCTCTGCTGGG 378
Qy 362 AGGACACCCAUGCUUUCUGACCACACAGGACAUUCAUCUGGGCGUGAACGAGUCACUGAC 421
||||||||||:||:::|:||||||||||||||::||:|:|||||:|||||||:|||:|||
Db 379 AGGACACCCATGCTTTCTGACCACACAGGACATTCATCTGGGCGTGAACGAGTCACTGAC 438
Qy 422 CGACACAGCUCGAGUCCUGAGCUCCAUGGCAGAUGCCGUGCUGGCACGGGUCUACAAACA 481
|||||||||:||||:||:||||:|||:||||||:||||:||:||||||||:|:|||||||
Db 439 CGACACAGCTCGAGTCCTGAGCTCCATGGCAGATGCCGTGCTGGCACGGGTCTACAAACA 498
Qy 482 GAGCGACCUGGAUACCCUGGCUAAGGAAGCAAGCAUCCCCAUCAUUAAUGGGCUGUCCGA 541
||||||||:|||:||||:|||:|||||||||||||:|||||:||::||:||||:|:||||
Db 499 GAGCGACCTGGATACCCTGGCTAAGGAAGCAAGCATCCCCATCATTAATGGGCTGTCCGA 558
Qy 542 CCUGUAUCACCCUAUCCAGAUUCUGGCCGAUUACCUGACCCUGCAGGAGCAUUAUUCUAG 601
||:|:|:|||||:|:|||||::|:||||||::|||:|||||:|||||||||::|::|:||
Db 559 CCTGTATCACCCTATCCAGATTCTGGCCGATTACCTGACCCTGCAGGAGCATTATTCTAG 618
Qy 602 UCUGAAAGGCCUGACACUGAGCUGGAUUGGGGACGGAAACAAUAUCCUGCACUCCAUUAU 661
:|:||||||||:|||||:||||:|||::||||||||||||||:|:||:||||:|||::|:
Db 619 TCTGAAAGGCCTGACACTGAGCTGGATTGGGGACGGAAACAATATCCTGCACTCCATTAT 678
Qy 662 GAUGUCUGCCGCUAAGUUUGGAAUGCAUCUGCAGGCAGCCACACCAAAAGGCUACGAACC 721
||:|:|:|||||:|||:::||||:|||:|:||||||||||||||||||||||:|||||||
Db 679 GATGTCTGCCGCTAAGTTTGGAATGCATCTGCAGGCAGCCACACCAAAAGGCTACGAACC 738
Qy 722 CGAUGCCAGUGUGACUAAGCUGGCCGAACAGUAUGCUAAAGAGAACGGCACUAAGCUGCU 781
|||:|||||:|:|||:||||:||||||||||:|:||:||||||||||||||:||||:||:
Db 739 CGATGCCAGTGTGACTAAGCTGGCCGAACAGTATGCTAAAGAGAACGGCACTAAGCTGCT 798
Qy 782 GCUGACCAAUGACCCUCUGGAGGCUGCACACGGAGGCAACGUCCUGAUCACUGAUACCUG 841
||:||||||:|||||:|:||||||:||||||||||||||||:||:||:|||:||:|||:|
Db 799 GCTGACCAATGACCCTCTGGAGGCTGCACACGGAGGCAACGTCCTGATCACTGATACCTG 858
Qy 842 GAUUUCCAUGGGCCAGGAGGAAGAGAAGAAAAAGCGCCUGCAGGCAUUCCAGGGGUACCA 901
||:::|||:|||||||||||||||||||||||||||||:|||||||::|||||||:||||
Db 859 GATTTCCATGGGCCAGGAGGAAGAGAAGAAAAAGCGCCTGCAGGCATTCCAGGGGTACCA 918
Qy 902 GGUGACAAUGAAAACUGCCAAGGUCGCCGCUUCUGAUUGGACUUUUCUGCAUUGUCUGCC 961
||:|||||:||||||:|||||||:||||||::|:||::||||::::|:|||::|:|:|||
Db 919 GGTGACAATGAAAACTGCCAAGGTCGCCGCTTCTGATTGGACTTTTCTGCATTGTCTGCC 978
Qy 962 CCGAAAACCUGAAGAGGUGGACGAUGAGGUCUUCUAUUCACCUAGGAGCCUGGUGUUUCC 1021
|||||||||:|||||||:||||||:||||:|::|:|::||||:|||||||:||:|:::||
Db 979 CCGAAAACCTGAAGAGGTGGACGATGAGGTCTTCTATTCACCTAGGAGCCTGGTGTTTCC 1038
Qy 1022 AGAAGCCGAGAAUCGCAAGUGGACAAUCAUGGCUGUGAUGGUGUCCCUGCUGACUGAUUA 1081
||||||||||||:||||||:||||||:||:|||:|:||:||:|:|||:||:|||:||::|
Db 1039 AGAAGCCGAGAATCGCAAGTGGACAATCATGGCTGTGATGGTGTCCCTGCTGACTGATTA 1098
Qy 1082 UUCCCCCCAGCUGCAGAAACCUAAGUUCUGAGCGGCCGCUUAAUUAAGCUGCCUUCUGCG 1141
::|||||||||:|||||||||:|||::|:||||||||||::||::||||:|||::|:|||
Db 1099 TTCCCCCCAGCTGCAGAAACCTAAGTTCTGAGCGGCCGCTTAATTAAGCTGCCTTCTGCG 1158
Qy 1142 GGGCUUGCCUUCUGGCCAUGCCCUUCUUCUCUCCCUUGCACCUGUACCUCUUGGUCUUUG 1201
||||::|||::|:|||||:||||::|::|:|:|||::|||||:|:|||:|::||:|:::|
Db 1159 GGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTG 1218
Qy 1202 AAUAAAGCCUGAGUAGGAAGUCUAG 1226
||:||||||:|||:||||||:|:||
Db 1219 AATAAAGCCTGAGTAGGAAGTCTAG 1243
Claim 29 is taught by Monahan as well. The sequence below is found in search database SEQ ID NO:8, RNI. It shows the relationship is 99.9% related between SEQ ID NO:111 and SEQ ID NO:8
RESULT 1
US-14-908-351-111
(NOTE: this sequence has 4 duplicates in the database searched.
See complete list at the end of this report)
Sequence 111, US/14908351
Patent No. 9867885
GENERAL INFORMATION
APPLICANT: PhaseRx, Inc.
TITLE OF INVENTION: BLOCK COPOLYMERS
FILE REFERENCE: 3800.PCT1
CURRENT APPLICATION NUMBER: US/14/908,351
CURRENT FILING DATE: 2016-01-28
NUMBER OF SEQ ID NOS: 122
SEQ ID NO 111
LENGTH: 1262
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: cDNA encoding human ornithine transcarbamylase, codon-optimized
for human expression
FEATURE:
NAME/KEY: promoter
LOCATION: (1)..(20)
OTHER INFORMATION: T7 promoter
Query Match 99.9%; Score 1225; Length 1262;
Best Local Similarity 100.0%;
Matches 1225; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCTGTTTAACCT 61
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 19 GGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCTGTTTAACCT 78
Qy 62 GAGGATTCTGCTGAACAACGCTGCTTTTCGGAACGGCCACAACTTTATGGTGCGGAACTT 121
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 79 GAGGATTCTGCTGAACAACGCTGCTTTTCGGAACGGCCACAACTTTATGGTGCGGAACTT 138
Qy 122 TCGGTGCGGACAGCCACTGCAGAACAAAGTGCAGCTGAAGGGGAGGGACCTGCTGACCCT 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 139 TCGGTGCGGACAGCCACTGCAGAACAAAGTGCAGCTGAAGGGGAGGGACCTGCTGACCCT 198
Qy 182 GAAAAATTTCACAGGAGAGGAAATCAAGTACATGCTGTGGCTGTCTGCCGATCTGAAGTT 241
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 199 GAAAAATTTCACAGGAGAGGAAATCAAGTACATGCTGTGGCTGTCTGCCGATCTGAAGTT 258
Qy 242 CCGGATCAAGCAGAAGGGCGAATATCTGCCACTGCTGCAGGGCAAAAGTCTGGGGATGAT 301
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 259 CCGGATCAAGCAGAAGGGCGAATATCTGCCACTGCTGCAGGGCAAAAGTCTGGGGATGAT 318
Qy 302 CTTCGAAAAGAGGAGTACTCGGACCAGACTGTCAACAGAGACTGGATTCGCTCTGCTGGG 361
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 319 CTTCGAAAAGAGGAGTACTCGGACCAGACTGTCAACAGAGACTGGATTCGCTCTGCTGGG 378
Qy 362 AGGACACCCATGCTTTCTGACCACACAGGACATTCATCTGGGCGTGAACGAGTCACTGAC 421
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 379 AGGACACCCATGCTTTCTGACCACACAGGACATTCATCTGGGCGTGAACGAGTCACTGAC 438
Qy 422 CGACACAGCTCGAGTCCTGAGCTCCATGGCAGATGCCGTGCTGGCACGGGTCTACAAACA 481
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 439 CGACACAGCTCGAGTCCTGAGCTCCATGGCAGATGCCGTGCTGGCACGGGTCTACAAACA 498
Qy 482 GAGCGACCTGGATACCCTGGCTAAGGAAGCAAGCATCCCCATCATTAATGGGCTGTCCGA 541
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 499 GAGCGACCTGGATACCCTGGCTAAGGAAGCAAGCATCCCCATCATTAATGGGCTGTCCGA 558
Qy 542 CCTGTATCACCCTATCCAGATTCTGGCCGATTACCTGACCCTGCAGGAGCATTATTCTAG 601
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 559 CCTGTATCACCCTATCCAGATTCTGGCCGATTACCTGACCCTGCAGGAGCATTATTCTAG 618
Qy 602 TCTGAAAGGCCTGACACTGAGCTGGATTGGGGACGGAAACAATATCCTGCACTCCATTAT 661
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 619 TCTGAAAGGCCTGACACTGAGCTGGATTGGGGACGGAAACAATATCCTGCACTCCATTAT 678
Qy 662 GATGTCTGCCGCTAAGTTTGGAATGCATCTGCAGGCAGCCACACCAAAAGGCTACGAACC 721
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 679 GATGTCTGCCGCTAAGTTTGGAATGCATCTGCAGGCAGCCACACCAAAAGGCTACGAACC 738
Qy 722 CGATGCCAGTGTGACTAAGCTGGCCGAACAGTATGCTAAAGAGAACGGCACTAAGCTGCT 781
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 739 CGATGCCAGTGTGACTAAGCTGGCCGAACAGTATGCTAAAGAGAACGGCACTAAGCTGCT 798
Qy 782 GCTGACCAATGACCCTCTGGAGGCTGCACACGGAGGCAACGTCCTGATCACTGATACCTG 841
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 799 GCTGACCAATGACCCTCTGGAGGCTGCACACGGAGGCAACGTCCTGATCACTGATACCTG 858
Qy 842 GATTTCCATGGGCCAGGAGGAAGAGAAGAAAAAGCGCCTGCAGGCATTCCAGGGGTACCA 901
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 859 GATTTCCATGGGCCAGGAGGAAGAGAAGAAAAAGCGCCTGCAGGCATTCCAGGGGTACCA 918
Qy 902 GGTGACAATGAAAACTGCCAAGGTCGCCGCTTCTGATTGGACTTTTCTGCATTGTCTGCC 961
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 919 GGTGACAATGAAAACTGCCAAGGTCGCCGCTTCTGATTGGACTTTTCTGCATTGTCTGCC 978
Qy 962 CCGAAAACCTGAAGAGGTGGACGATGAGGTCTTCTATTCACCTAGGAGCCTGGTGTTTCC 1021
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 979 CCGAAAACCTGAAGAGGTGGACGATGAGGTCTTCTATTCACCTAGGAGCCTGGTGTTTCC 1038
Qy 1022 AGAAGCCGAGAATCGCAAGTGGACAATCATGGCTGTGATGGTGTCCCTGCTGACTGATTA 1081
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1039 AGAAGCCGAGAATCGCAAGTGGACAATCATGGCTGTGATGGTGTCCCTGCTGACTGATTA 1098
Qy 1082 TTCCCCCCAGCTGCAGAAACCTAAGTTCTGAGCGGCCGCTTAATTAAGCTGCCTTCTGCG 1141
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1099 TTCCCCCCAGCTGCAGAAACCTAAGTTCTGAGCGGCCGCTTAATTAAGCTGCCTTCTGCG 1158
Qy 1142 GGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTG 1201
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1159 GGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTG 1218
Qy 1202 AATAAAGCCTGAGTAGGAAGTCTAG 1226
|||||||||||||||||||||||||
Db 1219 AATAAAGCCTGAGTAGGAAGTCTAG 1243
Both sequences comprise a 5’ UTR that causes the difference in the sequences.
ggaaauaagagagaaaagaagaguaagaagaaauauaagagccaccaug
However, if you were to replace this portion of the sequence with the 5’ UTR of Zhou et al, the sequence that would result is found in SEQ ID NO:4 and 8.
This alignment shows the alignment of the 5’ UTR of the instant claims and Zhou
Range 1: 1 to 46GraphicsNext MatchPrevious Match
Alignment statistics for match #1
NW Score
Identities
Gaps
Strand
39
46/47(98%)
1/47(2%)
Plus/Plus
Query 1 AGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACC 47
||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1 -GGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACC 46
Based on such teachings, it would have prima facie been obvious to one of ordinary skill in the art at the time the invention was made that OTC would be flanked by a 5’ UTR. As noted above: 1) Monahan teaches OTC with a 5’ UTR that overlaps those of the instant claims wherein the only difference is the first nucleoside; 2) However Zhou teaches use of the 5’ UTR for OTC that has 100% identity to that 5’ region of the instant 5’ region of SEQ ID NO:4. Thus, a person of ordinary skill in the art, absent evidence to the contrary, would have reasonably expected that the 5’UTR of Zhou et al would serve in the construct of Monahan et al.
As recited in claims 32 and 33, Zhou teaches that the sequence can be encoded in a plasmid and a host cell (see e.g. ¶0148 and 0413).
Claims 20, 41 and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Monahan et al (US 20160206750) in view of Zhou et al (U.S. 20200299652) as applied to claims 1, 2, 6, 7, 10, 15, 18, 29, 32, 33, 39 and 40 above, and further in view of Heyes et al (US 20160151284) and Schlake et al (WO 2019077001). This is a new rejection necessitated by applicants’ amendment.
The exact formulations for the LNP taught by Zhou were not provided for by Zhou. However, those claimed in claim 20 were known in the art. Heyes et al teach use of this formulation for mRNA delivery.
[0294] The following LNP formulation was used to prepare nucleic acid-lipid particles that were examined using Cryo-TEM: PEG-lipid (PEG2000-C-DMA) (1.6 mol %); 13-B43 lipid (54.6 mol %); cholesterol (32.8 mol %); and DSPC (10.9 mol %). LNP were prepared at a 0.95 mg (mRNA) scale, using the general procedures described above. The lipid stock was prepared in ethanol (12.6 mM total lipid). The mRNA stock was prepared at 0.366 mg/mL in 40 mM EDTA. The two stocks were combined and diluted into 4.9 mL of PBS. Buffer exchange was then performed via overnight bag dialysis against 10× volume of PBS. Samples were then concentrated to ˜1 mg/mL mRNA by centrifugation in Vivaspin-20 units (MWCO 100 k) from GE Healthcare. The LNP were then sterile filtered. Concentration of the LNP was determined using RiboGreen and a Varian Cary Eclipse Fluorimeter. Particle size and polydispersity were determined using a Malvern Nano Series Zetasizer.
As to enzymatic preparation of polyA sequences, Schlake et al teach this is a known method in the art, page 105 teaches that there are kits providing this operation.
Based on such teachings, it would have prima facie been obvious to one of ordinary skill in the art at the time the invention was made to incorporate the LNP of Heyes et al sand furthermore providing the polyA kit for enxzzymatic addition as taught by Schlake et al in the composition of Monahan in view of Zhou et al. Such a modification would have resulted in a composition encompassed by claim 20, 41 and 42. As noted above: 1) Monahan in view of Zhou et al teach a composition comprising mRNA requiring an LNP for delivery; 2) Heyes et al teach that mRNA can be delivered with an LNP comprising PEG2000-C-DMA: 13-B43-cholesterol and DSPG and 3) Schlake et al teach methods of enzymatically adding polyA and the target. Thus, a person of ordinary skill in the art, absent evidence to the contrary, would have reasonably expected that the detailed LNP of Heyes et al and means to aaeasily add a long polyA tail as taught by Schlake et al would be useful for the manufacture and delivery of OTC.
Response to Arguments
Applicant's arguments are two-fold. The first argument is that the art does not teach a polyA tail that is between 150-1000 nucleic acids long. Secondly applicants argue the application shows improved properties achieved with the claimed polyA tail. However, Zhou is clear that the polyA region can be up to 3000 nucleotides and as such provide unique properties.
[0363] Unique poly-A tail lengths provide certain advantages to the polynucleotides of the present invention. Generally, the length of a poly-A tail, when present, is greater than 30 nucleotides in length. In another embodiment, the poly-A tail is greater than 35 nucleotides in length (e.g., at least or greater than about 35, 40, 45, 50, 55, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1,000, 1,100, 1,200, 1,300, 1,400, 1,500, 1,600, 1,700, 1,800, 1,900, 2,000, 2,500, and 3,000 nucleotides).
This supposition is also supported by the art which teaches in PN 8,853,377 use of long polyA tails of at least 500 nucleotides wherein this teaching argues that the tail controls stability and influences the half-life of the mRNA and furthermore contemplates expression of OTC (see col 8, line 22-44 and col 14, lines 7-19). Expression models were shown to use longer mRNAs for OTC (see Prieve et al, Molecular Therapy, 2018, pages 801-813) with success (see page 810, col 1). As far back as 2006, the effect on expression and stability were shown to be enhanced with longer polyA tails (see Holtkamp, BLOOD, 2006, pages 4009-4017, especially abstract). Hence, the theoretical was shown in the practical. And at the time of filing the use of a long tail was known in the art for OTC expression.
As to unexpected results, applicants argue that the constructs had higher expression and lower immunogenicity with the longer tails (Figure 1). These are in fact not unexpected as shown above, it was common to use longer poly(A) tails for OTC mRNA expression. The essential impact of this was to increase stability and hence lower immunogenicity (both discussed ion page 92, col 2 of Meng et al (Tissue Engineering, 2019, pages 91-112). Hence, the impact of a longer poly(a) tail would have been known and expected to lead to improved stability and lower immunogenicity due to lack of degradation and by protection of the mRNA.
Double Patenting
A rejection based on double patenting of the "same invention" type finds its support in the language of 35 U.S.C. 101 which states that "whoever invents or discovers any new and useful process ... may obtain a patent therefor ..." (Emphasis added). Thus, the term "same invention," in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957); and In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970).
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. See 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) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130(b).
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 2 and 29, 30, 32 and 33 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-30 of U.S. 10,660,970 in view of Zhou et al (WO 2019104152). This rejection is amended based upon applicants’ amendment.
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claims because the examined claim is either anticipated by, or would have been obvious over, the reference claims. Although the conflicting claims are not identical, they are not patentably distinct from each other because the cited claims of the instant invention are generic to all that is recited in claims 1-30 of U.S. 10,660,970. That is, the cited claims of U.S. Patent 10,660,970 anticipate and fall entirely within the scope of the rejected claims of the instant application. The facts are set forth below. It is noted that the copending method claims are included as the safe harbor for non-statutory double patenting only applies for applications filed as divisional applications. The courts have determined the relevant claims of the two applications are not patentably distinct, when the claims at issue merely recited methods of administering therapeutically-effective amounts of the compositions claimed or means of making and no safe harbor exists.
Claim 2 recites a construct with an mRNA sequence comprising SEQ ID NO:4. This sequence with 99.5% identity to SEQ ID NO:114 is shown below in copending U.S. Patent 10,660,970 (U.S. application 16/543,324 and with full sequence provided for in search results associated with related application 14/908,351). While the sequence below shows the DNA sequence, the application intends that the sequence be RNA (see copending claim 1) is only different from the instant application by the 5’ UTR wherein Zhou teaches that the 5’ UTR can be one with the first G present as shown by Zhou above.
US-16-543-324-114
Filing date in PALM: 2019-08-16
Sequence 114, US/16543324
Patent No. 10660970
GENERAL INFORMATION
APPLICANT: GENEVANT SCIENCES GMBH
TITLE OF INVENTION: NUCLEIC ACID CONSTRUCTS AND METHODS OF USING THE SAME
FILE REFERENCE: 4170.0030004/BNC/PMR/LBR
CURRENT APPLICATION NUMBER: US/16/543,324
CURRENT FILING DATE: 2019-08-16
PRIOR APPLICATION NUMBER: US 15/827,793
PRIOR FILING DATE: 2017-11-30
PRIOR APPLICATION NUMBER: US 14/908,351
PRIOR FILING DATE: 2016-01-28
PRIOR APPLICATION NUMBER: PCT/US14/48839
PRIOR FILING DATE: 2014-07-30
PRIOR APPLICATION NUMBER: US 61/860,136
PRIOR FILING DATE: 2013-07-30
PRIOR APPLICATION NUMBER: US 61/868,122
PRIOR FILING DATE: 2013-08-21
NUMBER OF SEQ ID NOS: 122
SEQ ID NO 114
LENGTH: 1221
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: mRNA encoding human ornithine transcarbamylase, codon-optimized
for human expression
RESULT 2
US-14-908-351-114
(NOTE: this sequence has 4 duplicates in the database searched.
See complete list at the end of this report)
Sequence 114, US/14908351
Patent No. 9867885
GENERAL INFORMATION
APPLICANT: PhaseRx, Inc.
TITLE OF INVENTION: BLOCK COPOLYMERS
FILE REFERENCE: 3800.PCT1
CURRENT APPLICATION NUMBER: US/14/908,351
CURRENT FILING DATE: 2016-01-28
NUMBER OF SEQ ID NOS: 122
SEQ ID NO 114
LENGTH: 1221
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: mRNA encoding human ornithine transcarbamylase, codon-optimized
for human expression
Query Match 99.5%; Score 1220; Length 1221;
Best Local Similarity 100.0%;
Matches 1220; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAGAGCCACCAUGCUGUUUAACCU 61
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2 GGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAGAGCCACCAUGCUGUUUAACCU 61
Qy 62 GAGGAUUCUGCUGAACAACGCUGCUUUUCGGAACGGCCACAACUUUAUGGUGCGGAACUU 121
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 62 GAGGAUUCUGCUGAACAACGCUGCUUUUCGGAACGGCCACAACUUUAUGGUGCGGAACUU 121
Qy 122 UCGGUGCGGACAGCCACUGCAGAACAAAGUGCAGCUGAAGGGGAGGGACCUGCUGACCCU 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122 UCGGUGCGGACAGCCACUGCAGAACAAAGUGCAGCUGAAGGGGAGGGACCUGCUGACCCU 181
Qy 182 GAAAAAUUUCACAGGAGAGGAAAUCAAGUACAUGCUGUGGCUGUCUGCCGAUCUGAAGUU 241
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 182 GAAAAAUUUCACAGGAGAGGAAAUCAAGUACAUGCUGUGGCUGUCUGCCGAUCUGAAGUU 241
Qy 242 CCGGAUCAAGCAGAAGGGCGAAUAUCUGCCACUGCUGCAGGGCAAAAGUCUGGGGAUGAU 301
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 242 CCGGAUCAAGCAGAAGGGCGAAUAUCUGCCACUGCUGCAGGGCAAAAGUCUGGGGAUGAU 301
Qy 302 CUUCGAAAAGAGGAGUACUCGGACCAGACUGUCAACAGAGACUGGAUUCGCUCUGCUGGG 361
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 302 CUUCGAAAAGAGGAGUACUCGGACCAGACUGUCAACAGAGACUGGAUUCGCUCUGCUGGG 361
Qy 362 AGGACACCCAUGCUUUCUGACCACACAGGACAUUCAUCUGGGCGUGAACGAGUCACUGAC 421
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 362 AGGACACCCAUGCUUUCUGACCACACAGGACAUUCAUCUGGGCGUGAACGAGUCACUGAC 421
Qy 422 CGACACAGCUCGAGUCCUGAGCUCCAUGGCAGAUGCCGUGCUGGCACGGGUCUACAAACA 481
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 422 CGACACAGCUCGAGUCCUGAGCUCCAUGGCAGAUGCCGUGCUGGCACGGGUCUACAAACA 481
Qy 482 GAGCGACCUGGAUACCCUGGCUAAGGAAGCAAGCAUCCCCAUCAUUAAUGGGCUGUCCGA 541
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 482 GAGCGACCUGGAUACCCUGGCUAAGGAAGCAAGCAUCCCCAUCAUUAAUGGGCUGUCCGA 541
Qy 542 CCUGUAUCACCCUAUCCAGAUUCUGGCCGAUUACCUGACCCUGCAGGAGCAUUAUUCUAG 601
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 542 CCUGUAUCACCCUAUCCAGAUUCUGGCCGAUUACCUGACCCUGCAGGAGCAUUAUUCUAG 601
Qy 602 UCUGAAAGGCCUGACACUGAGCUGGAUUGGGGACGGAAACAAUAUCCUGCACUCCAUUAU 661
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 602 UCUGAAAGGCCUGACACUGAGCUGGAUUGGGGACGGAAACAAUAUCCUGCACUCCAUUAU 661
Qy 662 GAUGUCUGCCGCUAAGUUUGGAAUGCAUCUGCAGGCAGCCACACCAAAAGGCUACGAACC 721
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 662 GAUGUCUGCCGCUAAGUUUGGAAUGCAUCUGCAGGCAGCCACACCAAAAGGCUACGAACC 721
Qy 722 CGAUGCCAGUGUGACUAAGCUGGCCGAACAGUAUGCUAAAGAGAACGGCACUAAGCUGCU 781
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 722 CGAUGCCAGUGUGACUAAGCUGGCCGAACAGUAUGCUAAAGAGAACGGCACUAAGCUGCU 781
Qy 782 GCUGACCAAUGACCCUCUGGAGGCUGCACACGGAGGCAACGUCCUGAUCACUGAUACCUG 841
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 782 GCUGACCAAUGACCCUCUGGAGGCUGCACACGGAGGCAACGUCCUGAUCACUGAUACCUG 841
Qy 842 GAUUUCCAUGGGCCAGGAGGAAGAGAAGAAAAAGCGCCUGCAGGCAUUCCAGGGGUACCA 901
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 842 GAUUUCCAUGGGCCAGGAGGAAGAGAAGAAAAAGCGCCUGCAGGCAUUCCAGGGGUACCA 901
Qy 902 GGUGACAAUGAAAACUGCCAAGGUCGCCGCUUCUGAUUGGACUUUUCUGCAUUGUCUGCC 961
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 902 GGUGACAAUGAAAACUGCCAAGGUCGCCGCUUCUGAUUGGACUUUUCUGCAUUGUCUGCC 961
Qy 962 CCGAAAACCUGAAGAGGUGGACGAUGAGGUCUUCUAUUCACCUAGGAGCCUGGUGUUUCC 1021
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 962 CCGAAAACCUGAAGAGGUGGACGAUGAGGUCUUCUAUUCACCUAGGAGCCUGGUGUUUCC 1021
Qy 1022 AGAAGCCGAGAAUCGCAAGUGGACAAUCAUGGCUGUGAUGGUGUCCCUGCUGACUGAUUA 1081
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1022 AGAAGCCGAGAAUCGCAAGUGGACAAUCAUGGCUGUGAUGGUGUCCCUGCUGACUGAUUA 1081
Qy 1082 UUCCCCCCAGCUGCAGAAACCUAAGUUCUGAGCGGCCGCUUAAUUAAGCUGCCUUCUGCG 1141
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1082 UUCCCCCCAGCUGCAGAAACCUAAGUUCUGAGCGGCCGCUUAAUUAAGCUGCCUUCUGCG 1141
Qy 1142 GGGCUUGCCUUCUGGCCAUGCCCUUCUUCUCUCCCUUGCACCUGUACCUCUUGGUCUUUG 1201
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1142 GGGCUUGCCUUCUGGCCAUGCCCUUCUUCUCUCCCUUGCACCUGUACCUCUUGGUCUUUG 1201
Qy 1202 AAUAAAGCCUGAGUAGGAAG 1221
||||||||||||||||||||
Db 1202 AAUAAAGCCUGAGUAGGAAG 1221
This alignment shows the alignment of the 5’ UTR of the instant claims and Zhou
Range 1: 1 to 46GraphicsNext MatchPrevious Match
Alignment statistics for match #1
NW Score
Identities
Gaps
Strand
39
46/47(98%)
1/47(2%)
Plus/Plus
Query 1 AGGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACC 47
||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1 -GGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACC 46
Claim 29 recites an expression cassette with at least 85% identity to SEQ ID NO:8. This sequence is shown below in copending U.S. Patent 10,660,970 (U.S. application 16/543,324 and with full sequence provided for in search results associated with related application 14/908,351). The promoter as indicated below is T7 (see underlining) thus reading on claim 30. The cassette is part of a plasmid (oligonucleotide defined in the disclosure see bridging ¶ col 16-17 as a plasmid and claim 1 reciting an oligonucleotide) and host cell (claim 19).
US-16-543-324-111
Filing date in PALM: 2019-08-16
Sequence 111, US/16543324
Patent No. 10660970
GENERAL INFORMATION
APPLICANT: GENEVANT SCIENCES GMBH
TITLE OF INVENTION: NUCLEIC ACID CONSTRUCTS AND METHODS OF USING THE SAME
FILE REFERENCE: 4170.0030004/BNC/PMR/LBR
CURRENT APPLICATION NUMBER: US/16/543,324
CURRENT FILING DATE: 2019-08-16
PRIOR APPLICATION NUMBER: US 15/827,793
PRIOR FILING DATE: 2017-11-30
PRIOR APPLICATION NUMBER: US 14/908,351
PRIOR FILING DATE: 2016-01-28
PRIOR APPLICATION NUMBER: PCT/US14/48839
PRIOR FILING DATE: 2014-07-30
PRIOR APPLICATION NUMBER: US 61/860,136
PRIOR FILING DATE: 2013-07-30
PRIOR APPLICATION NUMBER: US 61/868,122
PRIOR FILING DATE: 2013-08-21
NUMBER OF SEQ ID NOS: 122
SEQ ID NO 111
LENGTH: 1262
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: cDNA encoding human ornithine transcarbamylase, codon-optimized
for human expression
FEATURE:
NAME/KEY: promoter
LOCATION: (1)..(20)
OTHER INFORMATION: T7 promoter
RESULT 1
US-14-908-351-111
(NOTE: this sequence has 4 duplicates in the database searched.
See complete list at the end of this report)
Sequence 111, US/14908351
Patent No. 9867885
GENERAL INFORMATION
APPLICANT: PhaseRx, Inc.
TITLE OF INVENTION: BLOCK COPOLYMERS
FILE REFERENCE: 3800.PCT1
CURRENT APPLICATION NUMBER: US/14/908,351
CURRENT FILING DATE: 2016-01-28
NUMBER OF SEQ ID NOS: 122
SEQ ID NO 111
LENGTH: 1262
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: cDNA encoding human ornithine transcarbamylase, codon-optimized
for human expression
FEATURE:
NAME/KEY: promoter
LOCATION: (1)..(20)
OTHER INFORMATION: T7 promoter
Query Match 99.9%; Score 1225; Length 1262;
Best Local Similarity 100.0%;
Matches 1225; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 GGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCTGTTTAACCT 61
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 19 GGAAATAAGAGAGAAAAGAAGAGTAAGAAGAAATATAAGAGCCACCATGCTGTTTAACCT 78
Qy 62 GAGGATTCTGCTGAACAACGCTGCTTTTCGGAACGGCCACAACTTTATGGTGCGGAACTT 121
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 79 GAGGATTCTGCTGAACAACGCTGCTTTTCGGAACGGCCACAACTTTATGGTGCGGAACTT 138
Qy 122 TCGGTGCGGACAGCCACTGCAGAACAAAGTGCAGCTGAAGGGGAGGGACCTGCTGACCCT 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 139 TCGGTGCGGACAGCCACTGCAGAACAAAGTGCAGCTGAAGGGGAGGGACCTGCTGACCCT 198
Qy 182 GAAAAATTTCACAGGAGAGGAAATCAAGTACATGCTGTGGCTGTCTGCCGATCTGAAGTT 241
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 199 GAAAAATTTCACAGGAGAGGAAATCAAGTACATGCTGTGGCTGTCTGCCGATCTGAAGTT 258
Qy 242 CCGGATCAAGCAGAAGGGCGAATATCTGCCACTGCTGCAGGGCAAAAGTCTGGGGATGAT 301
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 259 CCGGATCAAGCAGAAGGGCGAATATCTGCCACTGCTGCAGGGCAAAAGTCTGGGGATGAT 318
Qy 302 CTTCGAAAAGAGGAGTACTCGGACCAGACTGTCAACAGAGACTGGATTCGCTCTGCTGGG 361
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 319 CTTCGAAAAGAGGAGTACTCGGACCAGACTGTCAACAGAGACTGGATTCGCTCTGCTGGG 378
Qy 362 AGGACACCCATGCTTTCTGACCACACAGGACATTCATCTGGGCGTGAACGAGTCACTGAC 421
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 379 AGGACACCCATGCTTTCTGACCACACAGGACATTCATCTGGGCGTGAACGAGTCACTGAC 438
Qy 422 CGACACAGCTCGAGTCCTGAGCTCCATGGCAGATGCCGTGCTGGCACGGGTCTACAAACA 481
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 439 CGACACAGCTCGAGTCCTGAGCTCCATGGCAGATGCCGTGCTGGCACGGGTCTACAAACA 498
Qy 482 GAGCGACCTGGATACCCTGGCTAAGGAAGCAAGCATCCCCATCATTAATGGGCTGTCCGA 541
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 499 GAGCGACCTGGATACCCTGGCTAAGGAAGCAAGCATCCCCATCATTAATGGGCTGTCCGA 558
Qy 542 CCTGTATCACCCTATCCAGATTCTGGCCGATTACCTGACCCTGCAGGAGCATTATTCTAG 601
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 559 CCTGTATCACCCTATCCAGATTCTGGCCGATTACCTGACCCTGCAGGAGCATTATTCTAG 618
Qy 602 TCTGAAAGGCCTGACACTGAGCTGGATTGGGGACGGAAACAATATCCTGCACTCCATTAT 661
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 619 TCTGAAAGGCCTGACACTGAGCTGGATTGGGGACGGAAACAATATCCTGCACTCCATTAT 678
Qy 662 GATGTCTGCCGCTAAGTTTGGAATGCATCTGCAGGCAGCCACACCAAAAGGCTACGAACC 721
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 679 GATGTCTGCCGCTAAGTTTGGAATGCATCTGCAGGCAGCCACACCAAAAGGCTACGAACC 738
Qy 722 CGATGCCAGTGTGACTAAGCTGGCCGAACAGTATGCTAAAGAGAACGGCACTAAGCTGCT 781
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 739 CGATGCCAGTGTGACTAAGCTGGCCGAACAGTATGCTAAAGAGAACGGCACTAAGCTGCT 798
Qy 782 GCTGACCAATGACCCTCTGGAGGCTGCACACGGAGGCAACGTCCTGATCACTGATACCTG 841
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 799 GCTGACCAATGACCCTCTGGAGGCTGCACACGGAGGCAACGTCCTGATCACTGATACCTG 858
Qy 842 GATTTCCATGGGCCAGGAGGAAGAGAAGAAAAAGCGCCTGCAGGCATTCCAGGGGTACCA 901
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 859 GATTTCCATGGGCCAGGAGGAAGAGAAGAAAAAGCGCCTGCAGGCATTCCAGGGGTACCA 918
Qy 902 GGTGACAATGAAAACTGCCAAGGTCGCCGCTTCTGATTGGACTTTTCTGCATTGTCTGCC 961
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 919 GGTGACAATGAAAACTGCCAAGGTCGCCGCTTCTGATTGGACTTTTCTGCATTGTCTGCC 978
Qy 962 CCGAAAACCTGAAGAGGTGGACGATGAGGTCTTCTATTCACCTAGGAGCCTGGTGTTTCC 1021
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 979 CCGAAAACCTGAAGAGGTGGACGATGAGGTCTTCTATTCACCTAGGAGCCTGGTGTTTCC 1038
Qy 1022 AGAAGCCGAGAATCGCAAGTGGACAATCATGGCTGTGATGGTGTCCCTGCTGACTGATTA 1081
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1039 AGAAGCCGAGAATCGCAAGTGGACAATCATGGCTGTGATGGTGTCCCTGCTGACTGATTA 1098
Qy 1082 TTCCCCCCAGCTGCAGAAACCTAAGTTCTGAGCGGCCGCTTAATTAAGCTGCCTTCTGCG 1141
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1099 TTCCCCCCAGCTGCAGAAACCTAAGTTCTGAGCGGCCGCTTAATTAAGCTGCCTTCTGCG 1158
Qy 1142 GGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTG 1201
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1159 GGGCTTGCCTTCTGGCCATGCCCTTCTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTG 1218
Qy 1202 AATAAAGCCTGAGTAGGAAGTCTAG 1226
|||||||||||||||||||||||||
Db 1219 AATAAAGCCTGAGTAGGAAGTCTAG 1243
Additionally, if a patent resulting from the instant claims was issued and transferred to an assignee different from the assignee holding the U.S. Patent 10,660,970, then two different assignees would hold a patent to the claimed invention of U.S. Patent 10,660,970, and thus improperly there would be possible harassment by multiple assignees.
Response to Arguments
Applicant's arguments are the same as that above for the difference between the 5’ end of the sequence and the prior art. However, the rejection is amended to adapt the rejection to the newly amended claims.
Conclusion
No claims 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 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 MARIA MARVICH whose telephone number is (571)272-0774. The examiner can normally be reached 8 am - 5 pm.
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/MARIA MARVICH/Primary Examiner, Art Unit 1634
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