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 .
Election/Restrictions
Applicant’s species election of the CYP450 species of the polypeptide of SEQ ID NO: 338 and the AKR species of the polypeptide of SEQ ID NO: 340 in the reply filed on 11/03/2025 is acknowledged. In addition, nucleotide sequence of SEQ ID NO: 337 encoding SEQ ID NO: 338; and the nucleotide sequence of SEQ ID NO: 341 encoding SEQ ID NO: 340 are rejoined. Further, the polypeptide sequence of SEQ ID NO: 323, encoded by SEQ ID NO: 322 comprises both of the elected polypeptide sequences of SEQ ID NO: 338 and 340, and thus SEQ ID NOs: 322-323 are also rejoined in the election. Furthermore, SEQ ID NO: 326 encoding the AKR polypeptide of Papaver rhoeas of SEQ ID NO: 327 (Example 3 on page 52 of the specification) and SEQ ID NO: 324 encoding the CYP450 polypeptide of SEQ ID NO: 325 are also included in the species election as having a demonstrated specific activity (i.e. morphinan product formation) found in the Papaver somniferum native fusion polypeptide of SEQ ID NO: 323 comprising the elected CYP450 species of the polypeptide of SEQ ID NO: 338 and the AKR species of the polypeptide of SEQ ID NO: 340. Sequences 322-327, 337-338, and 340-341 are grouped together as species having the common specific activity of conversion of (S)-Reticuline to 1,2-Dehydroreticuline by a CYP450 polypeptide and conversion of 1,2-Dehydroreticuline to (R)-Reticuline by a AKR polypeptide.
Claims 85-101 are pending and examined.
Nucleotide and/or Amino Acid Sequence Disclosures
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification on page 55 are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
Claims 88, 90, and 93 are objected to because of the following informalities: SEQ ID NO: 184 is recited in the group of SEQ ID NO: 116-218 as encoding CYP450, but it also seems to encode an AKR as well and is much larger than a CYP450. Appropriate correction is required.
Claim Rejections - 35 USC § 112
Claims are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of CYP450 polynucleotides of SEQ ID NO: 116-218 encoding CYP450 polypeptides of SEQ ID NO: 219-321 and the Markush grouping of AKR polynucleotides of SEQ ID NO: 1-58 encoding AKR polypeptides of SEQ ID NO: 219-321 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: The generic non-structural designations AKR and CYP450 are descriptors that encompass polynucleotide sequences having various structures and functions that do not describe a common structure/function relationship.
Further, neither the prior art or the specification describes any particular region or regions of AKR sequences 1-58, 59-115, and 339 commonly held and resulting in the formation of a common product. For example, the art teaches the instant SEQ ID NO: 339 encoding a codeinone reductase (COR) AF108432.1 aligned below with instant SEQ ID NO: 339 and aligned as AF108432.1 vs nt 1738-2703 of instant SEQ ID NO: 322 also instant SEQ ID NO: 337.
Title: US-18-179-035-339 1_966 vs AF108432.1
Perfect score: 966
Sequence: 1 atggagagtaatggtgtacc..........tctgggatgagaaggattga 966
Scoring table: IDENTITY_NUC
Gapop 10.0 , Gapext 1.0
Searched: 1 seqs, 991 residues
Total number of hits satisfying chosen parameters: 2
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 2 summaries
Database : NASEQ2_02202026_145454.seq:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 966 100.0 991 1 NASEQ2_02202026_145454
ALIGNMENTS
Query Match 100.0%; Score 966; DB 1; Length 991;
Best Local Similarity 100.0%;
Matches 966; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ATGGAGAGTAATGGTGTACCTATGATCACTCTCAGTTCCGGCATTCGGATGCCTGCTTTA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ATGGAGAGTAATGGTGTACCTATGATCACTCTCAGTTCCGGCATTCGGATGCCTGCTTTA 60
Qy 61 GGTATGGGAACAGCTGAAACAATGGTAAAAGGAACAGAAAGAGAGAAATTGGCGTTTTTG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GGTATGGGAACAGCTGAAACAATGGTAAAAGGAACAGAAAGAGAGAAATTGGCGTTTTTG 120
Qy 121 AAAGCGATAGAGGTCGGTTACAGACACTTCGATACAGCTGCTGCATACCAAACTGAAGAG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AAAGCGATAGAGGTCGGTTACAGACACTTCGATACAGCTGCTGCATACCAAACTGAAGAG 180
Qy 181 TGTCTTGGTGAAGCTATAGCTGAAGCACTTCAACTTGGTCTAATAAAATCTCGAGATGAA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 TGTCTTGGTGAAGCTATAGCTGAAGCACTTCAACTTGGTCTAATAAAATCTCGAGATGAA 240
Qy 241 CTCTTCATCACTTCCAAGCTCTGGTGCGCTGATGCTCACGCTGATCTTGTCCTCCCTGCT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 CTCTTCATCACTTCCAAGCTCTGGTGCGCTGATGCTCACGCTGATCTTGTCCTCCCTGCT 300
Qy 301 CTTCAGAATTCTCTGAGGAATCTTAAATTGGACTATCTTGATCTATATTTGATACACCAT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 CTTCAGAATTCTCTGAGGAATCTTAAATTGGACTATCTTGATCTATATTTGATACACCAT 360
Qy 361 CCGGTAAGCTTGAAGCCAGGGAAGTTTGTTAACGAAATACCAAAGGATCATATCCTTCCA 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 CCGGTAAGCTTGAAGCCAGGGAAGTTTGTTAACGAAATACCAAAGGATCATATCCTTCCA 420
Qy 421 ATGGACTACAAATCTGTATGGGCAGCCATGGAAGAGTGTCAGACCCTTGGCTTCACTAGG 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 ATGGACTACAAATCTGTATGGGCAGCCATGGAAGAGTGTCAGACCCTTGGCTTCACTAGG 480
Qy 481 GCAATCGGGGTCTGTAATTTCTCATGCAAAAGGCTTCAAGAGTTGATGGAAACAGCCAAC 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GCAATCGGGGTCTGTAATTTCTCATGCAAAAGGCTTCAAGAGTTGATGGAAACAGCCAAC 540
Qy 541 AGCCCTCCAGTTGTGAATCAAGTGGAGATGAGCCCGACTTTACATCAAAAAAATCTGAGG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 AGCCCTCCAGTTGTGAATCAAGTGGAGATGAGCCCGACTTTACATCAAAAAAATCTGAGG 600
Qy 601 GAATATTGCAAGGCCAATAATATCATGATCACCGCACACTCAGTTTTGGGAGCCGTAGGT 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 GAATATTGCAAGGCCAATAATATCATGATCACCGCACACTCAGTTTTGGGAGCCGTAGGT 660
Qy 661 GCCGCCTGGGGCACCAATGCAGTTATGCATTCTAAGGTGCTTCACCAGATTGCTGTGGCC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 GCCGCCTGGGGCACCAATGCAGTTATGCATTCTAAGGTGCTTCACCAGATTGCTGTGGCC 720
Qy 721 AGAGGAAAATCTGTTGCCCAGGTTAGTATGAGATGGGTTTACCAGCAAGGCGCGAGTCTT 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 AGAGGAAAATCTGTTGCCCAGGTTAGTATGAGATGGGTTTACCAGCAAGGCGCGAGTCTT 780
Qy 781 GTGGTGAAAAGTTTCAATGAAGCGAGGATGAAGGAAAACCTTAAGATATTTGATTGGGAA 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 GTGGTGAAAAGTTTCAATGAAGCGAGGATGAAGGAAAACCTTAAGATATTTGATTGGGAA 840
Qy 841 CTAACGGCAGAAGACATGGAAAAGATCAGTGAGATTCCACAATCTAGAACAAGCTCTGCT 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 CTAACGGCAGAAGACATGGAAAAGATCAGTGAGATTCCACAATCTAGAACAAGCTCTGCT 900
Qy 901 GCTTTCTTGTTATCACCGACTGGACCTTTCAAAACTGAAGAAGAGTTCTGGGATGAGAAG 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 GCTTTCTTGTTATCACCGACTGGACCTTTCAAAACTGAAGAAGAGTTCTGGGATGAGAAG 960
Qy 961 GATTGA 966
||||||
Db 961 GATTGA 966
AF108432
LOCUS AF108432 1035 bp mRNA linear PLN 30-NOV-1999
DEFINITION Papaver somniferum NADPH-dependent codeinone reductase (cor1) mRNA,
cor1-1 allele, complete cds.
ACCESSION AF108432
VERSION AF108432.1
KEYWORDS .
SOURCE Papaver somniferum (opium poppy)
ORGANISM Papaver somniferum
Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
Spermatophyta; Magnoliophyta; eudicotyledons; Ranunculales;
Papaveraceae; Papaveroideae; Papaver.
REFERENCE 1 (bases 1 to 1035)
AUTHORS Unterlinner,B., Lenz,R. and Kutchan,T.M.
TITLE Molecular cloning and functional expression of codeinone reductase:
the penultimate enzyme in morphine biosynthesis in the opium poppy
Papaver somniferum
JOURNAL Plant J. 18 (5), 465-475 (1999)
PUBMED 10417697
REFERENCE 2 (bases 1 to 1035)
AUTHORS Unterlinner,B. and Kutchan,T.M.
TITLE Direct Submission
JOURNAL Submitted (23-NOV-1998) Laboratorium fuer Molekulare Biologie,
Universitaet Muenchen, Karlstrasse 29, Muenchen 80333, Germany
FEATURES Location/Qualifiers
source 1..1035
/organism="Papaver somniferum"
/mol_type="mRNA"
/db_xref="taxon:3469"
gene 1..1035
/gene="cor1"
/allele="1"
CDS 6..971
/gene="cor1"
/allele="1"
/EC_number="1.1.1.247"
/function="reduces codeinone to codeine in the penultimate
step in morphine biosynthesis"
/codon_start=1
/product="NADPH-dependent codeinone reductase"
/protein_id="AAF13736.1"
/translation="MESNGVPMITLSSGIRMPALGMGTAETMVKGTEREKLAFLKAIE
VGYRHFDTAAAYQTEECLGEAIA EALQLGLIKSRDELFITSKLWCADAHADLVLPALQ
NSLRNLKLDYLDLYLIHHPVSLKPGKFVNEIPKDHILPMDYKSVWAAMEECQTLGFTR
AIGVCNFSCKRLQELMETANSPPVVNQVEMSPTLHQKNLREYCKANNIMITAHSVLGA
VGAAWGTNAVMHSKVLHQIAVARGKSVAQVSMRWVYQQGASLVVKSFNEARMKENLKI
FDWELTAEDMEKISEIPQSRTSSAAFLLSPTGPFKTEEEFWDEKD"
Query Match 70.0%; Score 676.4; DB 106; Length 1035;
Best Local Similarity 81.3%;
Matches 785; Conservative 0; Mismatches 181; Indels 0; Gaps 0;
Qy 1 ATGGAGAGTAGTGGTGTACCAGTAATCACTCTGGGCTCGGGCAAGGTGATGCCTGTTCTG 60
|||||||||| ||||||||| | |||||||| | || |||| |||||||| | |
Db 6 ATGGAGAGTAATGGTGTACCTATGATCACTCTCAGTTCCGGCATTCGGATGCCTGCTTTA 65
Qy 61 GGCATGGGAACATTTGAGAAAGTTGGTAAAGGGTCCGAAAGAGAGAGGTTGGCGATTTTA 120
|| ||||||||| ||| | | | | ||||| | |||||||||| |||||| ||||
Db 66 GGTATGGGAACAGCTGAAACAATGGTAAAAGGAACAGAAAGAGAGAAATTGGCGTTTTTG 125
Qy 121 AAAGCGATAGAGGTGGGTTACAGATACTTCGATACAGCTGCTGCATACGAAACTGAAGAG 180
|||||||||||||| ||||||||| ||||||||||||||||||||||| |||||||||||
Db 126 AAAGCGATAGAGGTCGGTTACAGACACTTCGATACAGCTGCTGCATACCAAACTGAAGAG 185
Qy 181 GTTCTTGGAGAAGCTATTGCTGAAGCACTTCAACTTGGCCTAGTCAAATCTCGAGATGAA 240
|||||| |||||||| |||||||||||||||||||| ||| | |||||||||||||||
Db 186 TGTCTTGGTGAAGCTATAGCTGAAGCACTTCAACTTGGTCTAATAAAATCTCGAGATGAA 245
Qy 241 CTTTTCATCAGTTCCATGCTCTGGTGCACTGATGCTCACGCTGATCGTGTCCTCCTCGCT 300
|| ||||||| ||||| |||||||||| |||||||||||||||||| |||||||| |||
Db 246 CTCTTCATCACTTCCAAGCTCTGGTGCGCTGATGCTCACGCTGATCTTGTCCTCCCTGCT 305
Qy 301 CTTCAGAATTCGCTGAGGAATCTTAAATTGGAGTATGTGGATCTATATATGTTACCCTTC 360
||||||||||| |||||||||||||||||||| ||| | ||||||||| || ||| |
Db 306 CTTCAGAATTCTCTGAGGAATCTTAAATTGGACTATCTTGATCTATATTTGATACACCAT 365
Qy 361 CCGGCAAGCTTGAAGCCTGGGAAGATAACGATGGACATACCAGAGGAAGATATTTGTCGC 420
|||| |||||||||||| |||||| | | || |||||| |||| |||| ||
Db 366 CCGGTAAGCTTGAAGCCAGGGAAGTTTGTTAACGAAATACCAAAGGATCATATCCTTCCA 425
Qy 421 ATGGACTACAGGTCTGTATGGGCAGCCATGGAAGAGTGTCAAAACCTTGGCTTCACTAAA 480
|||||||||| ||||||||||||||||||||||||||||| | ||||||||||||||
Db 426 ATGGACTACAAATCTGTATGGGCAGCCATGGAAGAGTGTCAGACCCTTGGCTTCACTAGG 485
Qy 481 TCAATCGGTGTTAGCAATTTCTCCTGCAAAAAGCTTCAGGAATTGATGGCGACCGCCAAC 540
||||||| || | |||||||| ||||||| |||||| || ||||||| || ||||||
Db 486 GCAATCGGGGTCTGTAATTTCTCATGCAAAAGGCTTCAAGAGTTGATGGAAACAGCCAAC 545
Qy 541 ATCCCTCCAGCTGTGAATCAAGTGGAGATGAGCCCGGCTTTCCAACAAAAGAAGCTGAGA 600
| |||||||| ||||||||||||||||||||||||| |||| || ||||| || |||||
Db 546 AGCCCTCCAGTTGTGAATCAAGTGGAGATGAGCCCGACTTTACATCAAAAAAATCTGAGG 605
Qy 601 GAGTATTGCAACGCAAATAATATATTAGTCAGTGCAATCTCTGTACTGGGATCAAACGGA 660
|| |||||||| || |||||||| | ||| ||| ||| || ||||| | ||
Db 606 GAATATTGCAAGGCCAATAATATCATGATCACCGCACACTCAGTTTTGGGAGCCGTAGGT 665
Qy 661 ACCCCATGGGGCTCCAATGCAGTTTTGGGTTCTGAGGTGCTTAAGAAAATTGCTATGGCC 720
|| | |||||| ||||||||||| || |||| |||||||| | | |||||| |||||
Db 666 GCCGCCTGGGGCACCAATGCAGTTATGCATTCTAAGGTGCTTCACCAGATTGCTGTGGCC 725
Qy 721 AAAGGAAAATCTGTTGCTCAGGTTAGTATGAGATGGGTTTACGAGCAAGGCGCGAGTCTT 780
| ||||||||||||||| |||||||||||||||||||||||| |||||||||||||||||
Db 726 AGAGGAAAATCTGTTGCCCAGGTTAGTATGAGATGGGTTTACCAGCAAGGCGCGAGTCTT 785
Qy 781 GTGGTAAAAAGTTTCAGTGAAGAGAGATTGAGGGAAAACTTGAACATATTTGACTGGGAA 840
||||| |||||||||| ||||| ||| ||| ||||||| | || |||||||| ||||||
Db 786 GTGGTGAAAAGTTTCAATGAAGCGAGGATGAAGGAAAACCTTAAGATATTTGATTGGGAA 845
Qy 841 CTCACTAAGGAAGACCATGAAAAGATCGGTGAGATTCCACAGTGCAGAATCTTGAGTGCT 900
|| || |||||| ||||||||| ||||||||||||| | |||| ||||
Db 846 CTAACGGCAGAAGACATGGAAAAGATCAGTGAGATTCCACAATCTAGAACAAGCTCTGCT 905
Qy 901 TATTTTTTGGTCTCACCTAATGGACCTTTCAAATCTCAAGAAGAGTTGTGGGATGATGAA 960
||| ||| | ||||| | ||||||||||||| || |||||||||| |||||||| |
Db 906 GCTTTCTTGTTATCACCGACTGGACCTTTCAAAACTGAAGAAGAGTTCTGGGATGAGAAG 965
Qy 961 GCTTGA 966
| ||||
Db 966 GATTGA 971
AF108432
LOCUS AF108432 1035 bp mRNA linear PLN 30-NOV-1999
DEFINITION Papaver somniferum NADPH-dependent codeinone reductase (cor1) mRNA,
cor1-1 allele, complete cds.
ACCESSION AF108432
VERSION AF108432.1
KEYWORDS .
SOURCE Papaver somniferum (opium poppy)
ORGANISM Papaver somniferum
Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
Spermatophyta; Magnoliopsida; Ranunculales; Papaveraceae;
Papaveroideae; Papaver.
REFERENCE 1 (bases 1 to 1035)
AUTHORS Unterlinner,B., Lenz,R. and Kutchan,T.M.
TITLE Molecular cloning and functional expression of codeinone reductase:
the penultimate enzyme in morphine biosynthesis in the opium poppy
Papaver somniferum
JOURNAL Plant J. 18 (5), 465-475 (1999)
PUBMED 10417697
REFERENCE 2 (bases 1 to 1035)
AUTHORS Unterlinner,B. and Kutchan,T.M.
TITLE Direct Submission
JOURNAL Submitted (23-NOV-1998) Laboratorium fuer Molekulare Biologie,
Universitaet Muenchen, Karlstrasse 29, Muenchen 80333, Germany
FEATURES Location/Qualifiers
source 1..1035
/organism="Papaver somniferum"
/mol_type="mRNA"
/db_xref="taxon:3469"
gene 1..1035
/gene="cor1"
/allele="1"
CDS 6..971
/gene="cor1"
/allele="1"
/EC_number="1.1.1.247"
/function="reduces codeinone to codeine in the penultimate
step in morphine biosynthesis"
/codon_start=1
/product="NADPH-dependent codeinone reductase"
/protein_id="AAF13736.1"
/translation="MESNGVPMITLSSGIRMPALGMGTAETMVKGTEREKLAFLKAIE
VGYRHFDTAAAYQTEECLGEAIA EALQLGLIKSRDELFITSKLWCADAHADLVLPALQ
NSLRNLKLDYLDLYLIHHPVSLKPGKFVNEIPKDHILPMDYKSVWAAMEECQTLGFTR
AIGVCNFSCKRLQELMETANSPPVVNQVEMSPTLHQKNLREYCKANNIMITAHSVLGA
VGAAWGTNAVMHSKVLHQIAVARGKSVAQVSMRWVYQQGASLVVKSFNEARMKENLKI
FDWELTAEDMEKISEIPQSRTSSAAFLLSPTGPFKTEEEFWDEKD
Alignment Scores:
Length: 1035
Score: 1211.00 Matches: 232
Percent Similarity: 84.7% Conservative: 39
Best Local Similarity: 72.5% Mismatches: 49
Query Match: 73.7% Indels: 0
Gaps: 0
US-18-179-035-340 (1-321) x AF108432 (1-1035)
Qy 1 MetGluSerSerGlyValProValIleThrLeuGlySerGlyLysValMetProValLeu 20
|||||||||:::|||||||||:::||||||||| |||||| |||||| |||
Db 6 ATGGAGAGTAATGGTGTACCTATGATCACTCTCAGTTCCGGCATTCGGATGCCTGCTTTA 65
Qy 21 GlyMetGlyThrPheGluLysValGlyLysGlySerGluArgGluArgLeuAlaIleLeu 40
|||||||||||| ||| ::: ||||||:::|||||||||:::|||||| |||
Db 66 GGTATGGGAACAGCTGAAACAATGGTAAAAGGAACAGAAAGAGAGAAATTGGCGTTTTTG 125
Qy 41 LysAlaIleGluValGlyTyrArgTyrPheAspThrAlaAlaAlaTyrGluThrGluGlu 60
||||||||||||||||||||||||:::|||||||||||||||||||||:::|||||||||
Db 126 AAAGCGATAGAGGTCGGTTACAGACACTTCGATACAGCTGCTGCATACCAAACTGAAGAG 185
Qy 61 ValLeuGlyGluAlaIleAlaGluAlaLeuGlnLeuGlyLeuValLysSerArgAspGlu 80
|||||||||||||||||||||||||||||||||||||||:::|||||||||||||||
Db 186 TGTCTTGGTGAAGCTATAGCTGAAGCACTTCAACTTGGTCTAATAAAATCTCGAGATGAA 245
Qy 81 LeuPheIleSerSerMetLeuTrpCysThrAspAlaHisAlaAspArgValLeuLeuAla 100
|||||||||:::||| ||||||||| ||||||||||||||| |||||| |||
Db 246 CTCTTCATCACTTCCAAGCTCTGGTGCGCTGATGCTCACGCTGATCTTGTCCTCCCTGCT 305
Qy 101 LeuGlnAsnSerLeuArgAsnLeuLysLeuGluTyrValAspLeuTyrMetLeuProPhe 120
||||||||||||||||||||||||||||||:::|||:::|||||||||::::::
Db 306 CTTCAGAATTCTCTGAGGAATCTTAAATTGGACTATCTTGATCTATATTTGATACACCAT 365
Qy 121 ProAlaSerLeuLysProGlyLysIleThrMetAspIleProGluGluAspIleCysArg 140
||| |||||||||||||||||| :::||||||:::::: |||
Db 366 CCGGTAAGCTTGAAGCCAGGGAAGTTTGTTAACGAAATACCAAAGGATCATATCCTTCCA 425
Qy 141 MetAspTyrArgSerValTrpAlaAlaMetGluGluCysGlnAsnLeuGlyPheThrLys 160
|||||||||:::|||||||||||||||||||||||||||||| ||||||||||||:::
Db 426 ATGGACTACAAATCTGTATGGGCAGCCATGGAAGAGTGTCAGACCCTTGGCTTCACTAGG 485
Qy 161 SerIleGlyValSerAsnPheSerCysLysLysLeuGlnGluLeuMetAlaThrAlaAsn 180
:::||||||||| |||||||||||||||:::||||||||||||||| |||||||||
Db 486 GCAATCGGGGTCTGTAATTTCTCATGCAAAAGGCTTCAAGAGTTGATGGAAACAGCCAAC 545
Qy 181 IleProProAlaValAsnGlnValGluMetSerProAlaPheGlnGlnLysLysLeuArg 200
|||||| |||||||||||||||||||||||| |||||| ||||||
Db 546 AGCCCTCCAGTTGTGAATCAAGTGGAGATGAGCCCGACTTTACATCAAAAAAATCTGAGG 605
Qy 201 GluTyrCysAsnAlaAsnAsnIleLeuValSerAlaIleSerValLeuGlySerAsnGly 220
||||||||| ||||||||||||:::::::::||| ||||||||||||::: |||
Db 606 GAATATTGCAAGGCCAATAATATCATGATCACCGCACACTCAGTTTTGGGAGCCGTAGGT 665
Qy 221 ThrProTrpGlySerAsnAlaValLeuGlySerGluValLeuLysLysIleAlaMetAla 240
||||||:::|||||||||::: |||:::|||||| :::||||||:::|||
Db 666 GCCGCCTGGGGCACCAATGCAGTTATGCATTCTAAGGTGCTTCACCAGATTGCTGTGGCC 725
Qy 241 LysGlyLysSerValAlaGlnValSerMetArgTrpValTyrGluGlnGlyAlaSerLeu 260
:::|||||||||||||||||||||||||||||||||||||||:::|||||||||||||||
Db 726 AGAGGAAAATCTGTTGCCCAGGTTAGTATGAGATGGGTTTACCAGCAAGGCGCGAGTCTT 785
Qy 261 ValValLysSerPheSerGluGluArgLeuArgGluAsnLeuAsnIlePheAspTrpGlu 280
|||||||||||||||:::||| |||::::::||||||||| |||||||||||||||
Db 786 GTGGTGAAAAGTTTCAATGAAGCGAGGATGAAGGAAAACCTTAAGATATTTGATTGGGAA 845
Qy 281 LeuThrLysGluAspHisGluLysIleGlyGluIleProGlnCysArgIleLeuSerAla 300
|||||| |||||| ||||||||| |||||||||||| ||| ||||||
Db 846 CTAACGGCAGAAGACATGGAAAAGATCAGTGAGATTCCACAATCTAGAACAAGCTCTGCT 905
Qy 301 TyrPheLeuValSerProAsnGlyProPheLysSerGlnGluGluLeuTrpAspAspGlu 320
||||||:::|||||| ||||||||||||::::::|||||| ||||||::::::
Db 906 GCTTTCTTGTTATCACCGACTGGACCTTTCAAAACTGAAGAAGAGTTCTGGGATGAGAAG 965
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Indefiniteness
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.
Claims 98-101 are 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 98 is dependent from canceled base claim 1 rendering claim 98 and claims 99-101 dependent thereupon incomplete.
Written Description
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 85-97 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.
The claims are broadly drawn to recombinant nucleic acids and CYP450 and AKR nucleic acid sequences of unspecified substrate specificity and unspecified product formation; and chimeras and expression thereof.
Applicant describes a nucleotide sequence of SEQ ID NO: 337 encoding SEQ ID NO: 338; and the nucleotide sequence of SEQ ID NO: 341 encoding SEQ ID NO: 340; the polypeptide sequence of SEQ ID NO: 323, encoded by SEQ ID NO: 322 comprises both of the elected polypeptide sequences of SEQ ID NO: 338 and 340; SEQ ID NO: 326 encoding the AKR polypeptide of Papaver rhoeas of SEQ ID NO: 327 (see Example 3 on page 52 of the specification) and SEQ ID NO: 324 encoding the CYP450 polypeptide of SEQ ID NO: 325 are also directed to morphinan product formation found in the Papaver somniferum native fusion polypeptide of SEQ ID NO: 323 comprising the CYP83Y2 (DRS) polypeptide of SEQ ID NO: 338 and the AKR species of the (DRR) polypeptide of SEQ ID NO: 340; and thus sequences 322-327, 337-338, and 340-341 are a genus of species having the common specific activity of conversion of (S)-Reticuline to 1,2-Dehydroreticuline by a CYP450 polypeptide and conversion of 1,2-Dehydroreticuline to (R)-Reticuline by a AKR polypeptide. However, not every sequence recited in this genus and not every CYP450 and AKR as broadly claimed have any indication of a specific function other than having a generic CYP450 or AKR activity.
Applicants have claimed SEQ ID NO: 339, but it does not possess the same specific activity of the sequences exemplified in Examples 1-3 on pages 49-52 of the specification. See Unterlinner below, that shows SEQ ID NO: 339 encodes a codeinone reductase (COR) and not an enzyme that converts 1,2-Dehydroreticuline to (R)-Reticuline. The specification which teaches a "starting point" is not enough; that is little more than a research plan. See University of Rochester v. G.D. Searle & Co., 68 USPQ2d 1424, 1433 (DC WNY 2003) The court held that the disclosure of screening assays and general classes of compounds (such as the instantly claimed CYP450 and AKR polypeptides) was not adequate to describe compounds having the desired activity: without disclosure of which peptides, polynucleotides, or small organic molecules have the desired characteristic, and since Applicants have not demonstrated or described the invention sufficiently to show possession of the invention as broadly claimed, the claims failed to meet the description requirement of §112(a).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 85 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon (i.e. DNA) without significantly more. The claim(s) recite(s) “a recombinant nucleic acid” in claim 85 and in claim 86 “a complementary DNA (cDNA)”. This judicial exception is not integrated into a practical application because if claim 86 is further limiting with respect to the structure of the DNA being a cDNA, then interpreting “a recombinant nucleic acid comprising” of claim 85 would include genomic DNA indistinguishable from the naturally occurring forms of DNA; and thus claim 85 does not include additional elements that are sufficient to amount to significantly more than the judicial exception because no marked difference between a recombinant nucleic acid comprising SEQ ID NO: 322 as recited within the interpretation of claim 85 relative to claim 86, and the genomic sequence found in Papaver somniferum for example.
Claim Rejections - 35 USC § 102
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.
Claim(s) 85 and 86 are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by Unterlinner, B. et al., (1999) The Plant Journal; 18(5), pp. 465-475.
Th claims are drawn to recombinant nucleic acids comprising a nucleic acid sequence selected from the group consisting of:
(i) SEQ ID NO: 116-218, SEQ ID NO: 324, and SEQ ID NO: 337;
(ii) a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence at least 85% identical to the amino acid sequence set forth in SEQ ID NO: 219-321, SEQ ID NO: 325, and SEQ ID NO: 338;
(iii) SEQ ID NO: 1-58, SEQ ID NO: 326, SEQ ID NO: 328, and SEQ ID NO: 339;
(iv) a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence at least 85% identical to the amino acid sequence set forth in SEQ ID NO: 59-115, SEQ ID NO: 327; SEQ ID NO: 329, SEQ ID NO: 330, and SEQ ID NO: 340;
(v) SEQ ID NO: 322; and
(vi) a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence at least 85% identical to the amino acid sequence set forth in SEQ ID NO: 323.
Unterlinner teaches functional characterization of codeinone reductase (COR) an aldo keto reductase (i.e. AKR) from Papaver somniferum by recombinant expression in E. coli of AF108432.1 having 100% sequence identity to SEQ ID NO: 339 (see Abstract and beginning in the right column page 471 entire section titled Functional Characterization and alignment supra of SEQ ID NO: 339 and AF108432.1).
Claim(s) 85-91 are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by Kyrylenko, T.K. et al. (2005) Біополімери і клітина T. 21. No. 2; pp. 145-150.
The claims are broadly drawn to a chimeric nucleic acid or a recombinant expression vector comprising a first nucleic acid encoding a CYP450 polypeptide and/or a second nucleic acid sequence encoding an AKR polypeptide of unspecified substrate specificity or product formation that include CYP450 polynucleotides of SEQ ID NO: 116-218, 324, and 337; and AKR polynucleotides of SEQ ID NO: 1-58, 326, 328 and 339 further including a nucleic acid sequence capable of controlling expression in a host cell such as a promoter, a terminator, or a enhancer as recited in claim 91.
Kyrylenko teaches on pages 147-148 construction of a BAC library of the Papaver somniferum comprising integration sites i.e. restriction sites for integration into the bacterial genome.
Farrow, S.C. et al. Nature Chemical Biology, published online 1 July 2015; Vol. 11; pp. 728-732 provide evidence that the genome of Papaver somniferum comprised within the BAC library of Kyrylenko comprises the STORR fusion enzyme CYP450/AKR encoded by SEQ ID NO: 322 comprises the CYP450 coding sequence of SEQ ID NO: 337 and the AKR coding sequence of SEQ ID NO: 341; wherein nucleic acid sequences capable of controlling expression such as a stop codon are inherent features of the cloned chromosomal portions of Kyrylenko.
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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined 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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 85-97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3, 11, 14 and 15 of U.S. Patent No. 10190141. Although the claims at issue are not identical, they are not patentably distinct from each other because claim 3 of the ‘141 Patent recites a nucleic acid sequence encoding an amino acid sequence that is at least 85% identical to SEQ ID NO: 323 that teaches the recombinant expression vectors recited in instant claims 92-97 that comprise a first nucleic acid encoding a CYP450 polypeptide and a second nucleic acid encoding a AKR polypeptide such as the coding sequence of the natively occurring chimera/fusion polypeptide of SEQ ID NO: 322 from P. somniferum recited in instant claim 95 that encodes the polypeptide of SEQ ID NO: 323 recited in claims 3 and 14 of the ‘141 Patent. In addition, the recombinant nucleic acid sequences of claims 85-86 and the chimeric nucleic acid sequences of claims 87-91 are obvious since they also recite a broad genus of polynucleotide sequences that encompass the polynucleotide encoding a polypeptide having at least 85% sequence identity to the polypeptide of SEQ ID NO: 323.
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUSSELL KALLIS whose telephone number is (571)272-0798. The examiner can normally be reached Monday-Friday 8AM-5PM.
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/RUSSELL KALLIS/Primary Examiner, Art Unit 1663