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
For clarity of the record the following information regarding Election/Restriction is repeated from the Office action mailed 1 October 2024.
Applicant’s election without traverse of the species of HECT E3 UPL3b gene from corn as the species of HECT E3 UPL3 gene; SEQ ID NO:77 as the single HECT E3 UPL3 nucleic acid sequence; SEQ ID NO:83 as the single HECT E3 UPL3 polypeptide amino acid sequence; SEQ ID NO:123 as the single HECT E3 UPL3 mutated nucleic acid sequence; and residue 1776 to residue 1826 of SEQ ID NO:83 as the single active site of a HECT E3 UPL3 polypeptide in the reply filed on 20 May 2024 is acknowledged. During the course of examination, SEQ ID NO: 125 was rejoined.
Claims 1, 4, 11, 16, 19, 23, 29, 49, 50, 52, 53, 57, 59, 63, 64, 67, 70, 96, 97, and 98 are pending.
Claims 16, 53, 67, and 96 remain withdrawn as being drawn to nonelected species.
Claims 1, 4, 11, 19, 23, 29, 49, 50, 52, 57, 59, 63, 64, 70, 97, and 98 are pending and are examined to the extent that they read on the elected species.
The rejection of claims 1, 4, 11, 19, 23, 29, 50, 52, 57, 59, 63, 64, 70, 97, and 98 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in light of Applicant’s amendment of the claims.
Improper Markush Grouping Rejection
Claims 1, 4, 11, 19, 23, 29, 49, 50, 52, 57, 59, 63, 64, 70, 97, and 98 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 endogenous HECT E3 UPL polypeptides, nucleotides, active domains and mutated nucleotide sequences 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 sequences are distinct and are drawn to different plants (corn vs soy) and as such they don’t share a structural similarity. Furthermore, the active site regions and mutated sequences are not interchangeable between the two species and between the different HECT UPL genes.
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.
Response to Applicant’s Arguments:
Applicant argues on pages 12-14 that the sequences in claims 1, 4, 11, 19, 23, 29, 49, 50, 52, 57, 59, 63, 64, 70, 97, and 98 have a single structural similarity and a common use, and are proper Markush groupings. Applicant cites PTAB board decisions and case law in support of their arguments.
This is not found persuasive.
The MPEP states that where a Markush grouping describes part of a combination or process, the members following "selected from the group consisting of" (or a similar introductory phrase) must be substitutable, one for the other, with the expectation that the same intended result would be achieved. Multilayer Stretch Cling Film Holdings, Inc. v. Berry Plastics Corp., 831 F.3d 1350, 1357, 119 USPQ2d 1773, 1779 (Fed. Cir. 2016)("It is generally understood that … the members of the Markush group … are alternatively usable for the purposes of the invention … .") (see MPEP 2117.II Markush Claims).
Further, members of a Markush group share a "single structural similarity" when they belong to the same recognized physical or chemical class or to the same art-recognized class. A recognized physical class, a recognized chemical class, or an art-recognized class is a class wherein there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved.
Thus, a Markush grouping is ordinarily proper if all the members of the group belong to a recognized class (whether physical, chemical, or art recognized) and are disclosed in the specification to possess at least one property in common which is mainly responsible for their function in the claimed invention, and it is clear from their very nature or from the prior art that all members possess this property (see MPEP 2117.II Markush Claims – A. "Single Structural Similarity").
In the instant case, the sequences are not interchangeable. For example, one could not modify a HECT E3 UPL3 gene in corn by targeting a region which corresponds to a soybean HECT E3 UPL3. Likewise, one could not modify a soybean HECT E3 UPL3 gene to arrive at a modified corn HECT E3 UPL3 gene (i.e. SEQ ID NOs: 122-125).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 4, 11, 19, 23, 29, 49, 50, 52, 57, 59, 63, 64, 70, 97, and 98 are rejected under 35 U.S.C. 103 as being unpatentable over Bevan et al (WO-2018130828-A1) in view of Uniport Accession A0A1D6GXR8 (uniprot.org/UniProt/A0A1D6GXR8/entry; integrated 30 Nov 2016; see 02 June 2021 entry), Hua et al (WO2022136658 A1; priority date 23 December 2021, US listed as a designated state) and Downes et al 2003, The Plant Journal 35: 729-742. Due to Applicant' s amendment of the claims, the rejection is modified from the rejection set forth in the Office action mailed 16 May 2025. Applicant' s arguments filed 26 December 2024 have been fully considered but they are not persuasive.
The claims are broadly drawn to a plant or plant part thereof comprising at least one mutation in a region of endogenous Homologous to E6AP C-Terminus (HECT) E3 Ubiquitin Protein Ligase (UPL) gene encoding a HECT E3 UPL polypeptide wherein said region is located in a region of the polypeptide having at least 80% identity to a region of consecutive amino acids from residue 1776 to residue 1826 of SEQ ID NO:83; wherein the plant comprises two to four copies of the endogenous HECT E3 UPL gene encoding a HECT E3 UPL polypeptide and at least one of the copies comprises one or more mutations; wherein the at least one mutation is an out-of-frame or in-frame insertion or deletion; wherein the in-frame deletion results in a mutated gene with at least 90% to SEQ ID NOs: 123 or 125; wherein the endogenous HECT E3 UPL gene comprises a sequence having at least 80% sequence identity to the nucleotide sequence of SEQ ID NO: 77 and/or encodes a sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 83; wherein said plant has improved yield traits; and a plant regenerated from said plant comprising an endogenous HECT E3 UPL gene encoding a HECT E3 UPL polypeptide comprising one or more mutations in said region and wherein the regenerated plant comprises a mutated gene with at least 90% to SEQ ID NOs: 123 or 125 . The claims are further drawn to methods for making said plants by editing via cleaving a specific target site in within an endogenous HECT E3 UPL gene wherein the edit is in an active site located in a region of the polypeptide having at least 80% identity to a region of consecutive amino acids from residue 1776 to residue 1826 of SEQ ID NO:83; wherein the endogenous HECT E3 UPL gene comprises a sequence having at least 80% sequence identity to the nucleotide sequence of SEQ ID NO: 77 and/or encodes a sequence having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 83; wherein the edited plant has improved yield traits; and wherein the method comprises contacting a target site with a nuclease comprising a cleavage domain and a nucleic acid biding domain.
Bevan et al teaches a method of increasing seed yield in a plant by reducing expression of a HECT E3 UPL3 gene by introducing at least one mutation into the gene, including deletions (claims 1, 5, 7 and 30; page 23). Bevan et al teaches said method using target gene editing by CRISPR/CAS9, TALEN or ZFNS, which inherently comprise a nuclease comprising a cleavage domain and a nucleic acid biding domain (claim 9), wherein the method increases seed yield (claim 12). Bevan et al teaches that the plant can be maize (claim 14). Bevan et al teaches plants comprising said HECT E3 UPL3 comprising a mutation and wherein the plant is maize (claims 16-17, 25). Bevan et al teaches that mutations can be in the HECT domain and can be an amino acid change in a highly conserved region (page 23). Bevan et al teaches that their methods encompass regenerating said modified plants with reduced expression of a HECT E3 UPL3 gene (page 6, lines 25-28).
Bevan et al does not teach a sequence with at least 80% identity to SEQ ID NO: 83.
Bevan et al does not teach making mutation in a region of the HECT E3 UPL polypeptide, wherein the wherein said region is located in a region of the polypeptide having at least 80% identity to a region of consecutive amino acids from residue 1776 to residue 1826 of SEQ ID NO:83.
Uniport Accession A0A1D6GXR8 (uniprot.org/uniprotkb/A0A1D6GXR8/entry; integrated 30 Nov 2016; see 02 June 2021 entry) teaches a peptide encoding a maize HECT E3 UPL gene that has 100% sequence identity to SEQ ID NO: 83.
A0A1D6GXR8_MAIZE
ID A0A1D6GXR8_MAIZE Unreviewed; 1833 AA.
AC A0A1D6GXR8;
DT 30-NOV-2016, integrated into UniProtKB/TrEMBL.
DT 30-NOV-2016, sequence version 1.
DT 27-MAR-2024, entry version 37.
DE RecName: Full=HECT-type E3 ubiquitin transferase {ECO:0000256|ARBA:ARBA00012485};
DE EC=2.3.2.26 {ECO:0000256|ARBA:ARBA00012485};
GN ORFNames=ZEAMMB73_Zm00001d014920 {ECO:0000313|EMBL:AQK67610.1};
FT ACT_SITE 1800
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00104"
SQ SEQUENCE 1833 AA; 198791 MW; 7F6F4EB8E6F8C082 CRC64;
Query Match 100.0%; Score 9259; Length 1833;
Best Local Similarity 100.0%;
Matches 1833; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 METRSSSRKRAAAAASSSASKRPRRNSSSSSSAPPRQQPPMEPSPSSRRRSRAAAADKGK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 METRSSSRKRAAAAASSSASKRPRRNSSSSSSAPPRQQPPMEPSPSSRRRSRAAAADKGK 60
Qy 61 DPDPASSDHPSPPAPDDDADVTFPQPFTSASTALQGLLRRLGAGLDDLLPSSSSAPSSAT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DPDPASSDHPSPPAPDDDADVTFPQPFTSASTALQGLLRRLGAGLDDLLPSSSSAPSSAT 120
Qy 121 SGHLKRILAGLQAHGDESRQLQSLMQLCEMLSIGTEDSLAAFPVDAFVPILVGMLGREDE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SGHLKRILAGLQAHGDESRQLQSLMQLCEMLSIGTEDSLAAFPVDAFVPILVGMLGREDE 180
Qy 181 PATAGASPDVMLLAARALSNLVDVLPSSCSAVVHYGAIQCFCARLLTIEYMDLAEQSLQA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 PATAGASPDVMLLAARALSNLVDVLPSSCSAVVHYGAIQCFCARLLTIEYMDLAEQSLQA 240
Qy 241 LKKISLEHPTACLRAGALMAVLSYLDFFSTGVQRVALSTAANICRKLPSDASEFVMEAVP 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LKKISLEHPTACLRAGALMAVLSYLDFFSTGVQRVALSTAANICRKLPSDASEFVMEAVP 300
Qy 301 LLTNLLNHHDSKVLEHASVCLTRIAEAFAYYPDKLDELCNHGLVAQAASLIAVGNSSGQT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 LLTNLLNHHDSKVLEHASVCLTRIAEAFAYYPDKLDELCNHGLVAQAASLIAVGNSSGQT 360
Qy 361 SLSTSTYTGLIRLLSICASGSLLAVKTLLLLGISGTLKDILSGSALISGTSVSPAVTRPA 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 SLSTSTYTGLIRLLSICASGSLLAVKTLLLLGISGTLKDILSGSALISGTSVSPAVTRPA 420
Qy 421 DQMFEIVSLADDLLPHIPARIIKLPTYYHTYKGSSTKKSASIKQEGGGSTGNERSGRERL 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 DQMFEIVSLADDLLPHIPARIIKLPTYYHTYKGSSTKKSASIKQEGGGSTGNERSGRERL 480
Qy 481 LREQPELLQQFGMDLLPTMTQVYGSSVNAPIRHKCLSIIGKLMYYSSAETIQSLLGTTNI 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 LREQPELLQQFGMDLLPTMTQVYGSSVNAPIRHKCLSIIGKLMYYSSAETIQSLLGTTNI 540
Qy 541 SSFLAGILAWKDPQVLIPALQIAEIMMEKLPETFSKLFVREGVVHAVESLICSESSNKMP 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 SSFLAGILAWKDPQVLIPALQIAEIMMEKLPETFSKLFVREGVVHAVESLICSESSNKMP 600
Qy 601 SQVPPQDKDKDSAMPSRSRRQRRRAGAVAAENSSLDESNSSNLGVMCSTATASEAPNTSL 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 SQVPPQDKDKDSAMPSRSRRQRRRAGAVAAENSSLDESNSSNLGVMCSTATASEAPNTSL 660
Qy 661 RFTVSDHAKSFKDKYFPADTDSSDIGFTDDLLKLRALCAKLNTVSENVKTKAKGKSKAIS 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 RFTVSDHAKSFKDKYFPADTDSSDIGFTDDLLKLRALCAKLNTVSENVKTKAKGKSKAIS 720
Qy 721 TNFLDISIDVEEQLDKIISEMLSELSKVNGVSTFEFIRSGVVIALLDYLSCGTFGKEKVS 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 TNFLDISIDVEEQLDKIISEMLSELSKVNGVSTFEFIRSGVVIALLDYLSCGTFGKEKVS 780
Qy 781 EGNLSQLRQQALRRYKTFISVALSIDHGRDETPMALLVQKLQSALSSLERFPVVLSQSSR 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 EGNLSQLRQQALRRYKTFISVALSIDHGRDETPMALLVQKLQSALSSLERFPVVLSQSSR 840
Qy 841 IGIGGSRLTSGLSALAQPFKLRLSRAQGEKSLRDYSSNIVLIDPFASLASVEEFLWPRVQ 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 IGIGGSRLTSGLSALAQPFKLRLSRAQGEKSLRDYSSNIVLIDPFASLASVEEFLWPRVQ 900
Qy 901 RSEVASKPIIPSGNNSESGVPGTTAGASLTAAMAQSGRRPTTRSKSSAAGGLTSKKDSHD 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 RSEVASKPIIPSGNNSESGVPGTTAGASLTAAMAQSGRRPTTRSKSSAAGGLTSKKDSHD 960
Qy 961 ESTSTAKGKGKAIVKPNSDESKGPNTRNAAHQKSASEKDLEMKQAHGHSSSEDEELDTSP 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 ESTSTAKGKGKAIVKPNSDESKGPNTRNAAHQKSASEKDLEMKQAHGHSSSEDEELDTSP 1020
Qy 1021 VEIDDALMIDDDDISDDDDDDDDDHEVLQEGSLPICSQDGVHDVKLGDADESNIGSATFS 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 VEIDDALMIDDDDISDDDDDDDDDHEVLQEGSLPICSQDGVHDVKLGDADESNIGSATFS 1080
Qy 1081 HAQPSSGSGARNTSSRGPDSTEFRSMGTFGSRGAMSFVAATMAGLASVGGRSVRGVRDRR 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 HAQPSSGSGARNTSSRGPDSTEFRSMGTFGSRGAMSFVAATMAGLASVGGRSVRGVRDRR 1140
Qy 1141 GLSLGGSMNDHNKLIFTAGGKQLNKHLTVYQAIQRQLMLDEDDEERFNGSDIPNDGNRFW 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 GLSLGGSMNDHNKLIFTAGGKQLNKHLTVYQAIQRQLMLDEDDEERFNGSDIPNDGNRFW 1200
Qy 1201 GDVFTITYQKADNQVEKGCQGTSTSLNIKSDSYRSISEAQGVSLLDSILQGELPCDLERT 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 GDVFTITYQKADNQVEKGCQGTSTSLNIKSDSYRSISEAQGVSLLDSILQGELPCDLERT 1260
Qy 1261 NSTYNILALLRILEGLNQLSPRLRVQGASDDFAEGKINTLDELYRTGAKVPSEVFVNSKL 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 NSTYNILALLRILEGLNQLSPRLRVQGASDDFAEGKINTLDELYRTGAKVPSEVFVNSKL 1320
Qy 1321 TPKLARQMQDVLALCSGSLPSWCYQMTKACPFLFPFETRRQYFYSTAFGLSRALNRLQQQ 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 TPKLARQMQDVLALCSGSLPSWCYQMTKACPFLFPFETRRQYFYSTAFGLSRALNRLQQQ 1380
Qy 1381 QSDNHSSGGEREVRFGRLQRQKVRVSRNRILDSAAKVMEMFSSQRAVLEVEYFGEVGTGL 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 QSDNHSSGGEREVRFGRLQRQKVRVSRNRILDSAAKVMEMFSSQRAVLEVEYFGEVGTGL 1440
Qy 1441 GPTLEFYTLLSHELQCAQLGLWRATSSYDSGLHTDMKDVIRLDPEDGSSGKELNTDLPGD 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 GPTLEFYTLLSHELQCAQLGLWRATSSYDSGLHTDMKDVIRLDPEDGSSGKELNTDLPGD 1500
Qy 1501 GMYLIQAPLGLFPRPWPPKVDTSEGSRFFKVLEYFRLIGQVIAKVLQDGRLLDLPLSTAF 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1501 GMYLIQAPLGLFPRPWPPKVDTSEGSRFFKVLEYFRLIGQVIAKVLQDGRLLDLPLSTAF 1560
Qy 1561 YKLILGQELDLFDIVSFDSEFGKTLQELQVLVERKQFLESTSGKNQLQVADLCFHGASIE 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1561 YKLILGQELDLFDIVSFDSEFGKTLQELQVLVERKQFLESTSGKNQLQVADLCFHGASIE 1620
Qy 1621 DLCLDFTLPGYPDYVLKEGEGGTIVNIYNLEEYITLVVDATVKSGIKRQVEAFRSGFNQV 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1621 DLCLDFTLPGYPDYVLKEGEGGTIVNIYNLEEYITLVVDATVKSGIKRQVEAFRSGFNQV 1680
Qy 1681 FDMSSLHIFSPQELDYLICGRQEIWESESLVDNIKFDHGYTAKSPAIVNLLEILSEFTPE 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1681 FDMSSLHIFSPQELDYLICGRQEIWESESLVDNIKFDHGYTAKSPAIVNLLEILSEFTPE 1740
Qy 1741 QQHAFCQFVTGAPRLPHGGLAALSPKLTIVRKHPSSAVNTSNSTGAVESADDDLPSVMTC 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1741 QQHAFCQFVTGAPRLPHGGLAALSPKLTIVRKHPSSAVNTSNSTGAVESADDDLPSVMTC 1800
Qy 1801 ANYLKLPPYSTKEIMRKKLLYAILEGRGSFDLS 1833
|||||||||||||||||||||||||||||||||
Db 1801 ANYLKLPPYSTKEIMRKKLLYAILEGRGSFDLS 1833
Uniport Accession A0A1D6GXR8 teaches that the polypeptide taught therein is encoded by Zm00001d014920, the same genomic sequence represented by SEQ ID NO: 77 and which encodes SEQ ID NO: 83 (see instant specification, Example 5, Table 4). Uniport Accession A0A1D6GXR8 teaches that the polypeptide taught therein has an active site at residue 1800, a cysteine.
Hua et al teaches modified plants and method for making said plants, comprising at least one mutation in a HECT E3 UPL2 gene, wherein the mutation is a deletion of part of the HECT domain, and that said plants have increased yield and wherein the plants are maize (Claims 1-5, 7-8, 10-16, 19-20).
Hua et al teaches substitution or deletion of a conserved cysteine in the HECT domain required for ubiquitin ligase activity (page 21, lines 15-25; page 49, lines 14-28).
Downes et al teach HECT E3 UPL3 polypeptides are known to have a conserved HECT domain, which comprise a conserved region around an invariant “active-site/catalytic site” cysteine that is required for the protein to function in ubiquitination (See Downes et al 2003, The Plant Journal 35: 729-742; page 731, column 1, “Results”, first paragraph; alignment and figure caption of Figure 1).
At the time of filing, it would have been prima facie obvious to one of ordinary skill in the art to modify the methods and plants of Bevan et al to target the gene encoding the peptide of Unipr0t Uniport Accession A0A1D6GXR8. One would have been motivated to do so because Bevan et al suggest that their methods and plants can be directed to maize and Uniport Accession A0A1D6GXR8 teaches that their peptide is a HECT E3 UPL3 peptide.
It would have been further prima facie obvious to target an active site in a HECT E3 UPL3 because said peptides require the active site to function and given the teachings of the prior art. Bevan et al teaches that the mutation can be targeted to a HECT domain or conserved amino acid therein. Hua et al teaches mutating a conserved Cysteine in a HECT domain to abolish function in HECT E3 UPL polypeptides. Downes et al teaches that HECT E3 UPL3 polypeptides comprise an “active site” Cysteine required for its function. Uniport Accession A0A1D6GXR8 teaches the location of said active site.
Regarding the limitations drawn to “in-frame deletion”, it would be obvious to make such a deletion as deletions are either in-frame or frame-shift mutations. Doing so would be a matter of design choice.
Regarding the limitations drawn to SEQ ID NO: 123 and 125, Examiner notes that the polypeptide taught by Uniport Accession A0A1D6GXR8 is encoded by the same polynucleotide represented by SEQ ID NO: 77. SEQ ID NO: 123 differs from SEQ ID NO: 77 by only the deletion of six nucleic acids, including the active site. Thus, practicing the methods taught by the combined prior art references, or making the plants taught by the prior art references (e.g. deleting the nucleotides encoding the active site cysteine) would result inherently in a sequence with at least 90% sequence identity to SEQ ID NO: 123.
Therefore, the combined prior art references make obvious all the limitations of claims 1, 4, 11, 19, 23, 29, 49, 50, 52, 57, 59, 63, 64, 70, 97, and 98.
Response to Applicant’s arguments:
In the Remarks filed on 14 August 2015, Applicant argues that Bevan describes an Arabidopsis T-DNA insertion mutant of UPL with a complete knockdown of UPL3 expression, and that one of skill in the art would understand that T-DNA insertion mutagenesis generates random mutations and would thus not be used to for generating targeted mutations with any predictability (page 15, third paragraph). Applicant further urges that, given this fact, there would be no motivation to combine the teachings of Bevan with UPL3 protein taught by Uniport Accession A0A1D6GXR8 with any reasonable expectation of success. Applicant continues that because the UPL3 protein taught by Bevan and the UPL3 protein taught by Uniport Accession A0A1D6GXR8 have only 65% sequence identity, there would have been unpredictability and no reasonable expectation of success to arrive at the instantly claimed invention (page 15, final paragraph).
Applicant argues that Hua does not remedy this deficiency because Hua teaches random mutagenesis, which, like T-DNA insertional mutagenesis, is random and thus there would be no motivation to combine the teachings of the prior art references to arrive at the instantly claimed invention with any reasonable expectation of success (page 16, paragraph 1). Applicant further argues that the rice UPL2 protein taught by Hua has only 25% sequence identity to UPL3 protein taught by UniProt Accession A0A1D6GXR8, and because of the differences in the proteins taught by Bevan, UniProt Accession A0A1D6GXR8, and Hua there would have been unpredictability and no reasonable expectation of success to arrive at the instantly claimed invention (page 16, second paragraph).
Applicant argues that because the UPL3 protein taught by Downes and the UPL3 protein taught by Uniport Accession A0A1D6GXR8 have only 65% sequence identity, there would have been no reason to combine Downes with the other prior art references with any reasonable expectation of success to arrive at the instantly claimed invention (page 16, final paragraph).
Applicant urges that, even if the prior art refences were combined, because of differences in the proteins taught in the prior art refences there would have been unpredictability and no reasonable expectation of success to arrive at the instantly claimed invention (page 17, first paragraph).
This is not found persuasive.
As a first matter, In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Regarding the arguments directed to the teachings of Bevan et al, while Bevan et al may disclose an Arabidopsis T-DNA insertion mutant of UPL with a complete knockdown of UPL3 expression, these are not the only teachings found in Bevan et al. As set forth above in the 35 U.S.C. 103 rejection, Bevan et al also teaches a method of increasing seed yield in a plant by reducing expression of a HECT E3 UPL3 gene by introducing at least one mutation into the gene, including deletions and said method using target gene editing by CRISPR/CAS9, TALEN or ZFNS, which inherently comprise a nuclease comprising a cleavage domain and a nucleic acid biding domain, wherein the method increases seed yield. Bevan et al further teaches that the plant can be maize; teaches plants comprising said HECT E3 UPL3 comprising a mutation and wherein the plant is maize; and teaches that mutations can be in the HECT domain and can be an amino acid change in a highly conserved region. Bevan et al teaches further that their methods encompass regenerating said modified plants with reduced expression of a HECT E3 UPL3 gene. Given that Bevan et al teaches a method of non-random, targeted gene editing in a UPL3 gene and teaches doing so in a maize plant (among other things), one would have sufficient motivation and a reasonable expectation of success to combine the teachings of Bevan et al with the teachings of UniProt Accession A0A1D6GXR8, which is a maize UPL3 gene/protein, even though the one protein taught by Beavan et al, and which is not cited in the rejection, has low sequence identity to the protein taught by UniProt Accession A0A1D6GXR8,
Regarding the teachings of Hua et al, Hua is not relied upon to teach a mutagenesis method or a protein. Rather, Hua et al teaches modified plants and methods for making said plants, comprising at least one mutation in a HECT E3 UPL2 gene, wherein the mutation is a deletion of part of the HECT domain, and that said plants have increased yield and wherein the plants are maize. Hua et al further teaches substitution or deletion of a conserved cysteine in the HECT domain required for ubiquitin ligase activity. One would have been motived to combine the teachings of Hua et al (specifically, mutating a conserved Cysteine in a HECT domain to abolish function in HECT E3 UPL polypeptides) with the other prior art references given that Bevan et al teaches that the mutation taught therein can be targeted to a HECT domain or conserved amino acid therein, Downes et al teaches that HECT E3 UPL3 polypeptides comprise an “active site” Cysteine required for its function and Uniport Accession A0A1D6GXR8 teaches the location of said active site. The similarity of the protein taught by Hua et al to other proteins is immaterial here as the conserved Cysteine of the HECT domain is common to both UPL2 and UPL3 genes.
Regarding the arguments directed to the teachings of Downes et al, while the UPL3 protein taught by Uniport Accession A0A1D6GXR8 and the UPL3 of Downes et al have only 65% sequence identity, Downes is cited for teachings drawn to the conserved HECT domains of HECT E3 UPL3 polypeptides, generally, which comprise a conserved region around an invariant “active-site/catalytic site” cysteine that is required for the protein to function in ubiquitination. Thus, even though the proteins share low sequence identity, they both comprise the conserved domain and conserved active-site/catalytic site” cysteine.
Finally, Applicant argues that even if the prior art refences were combined, because of differences in the proteins taught in the prior art refences there would have been unpredictability and no reasonable expectation of success to arrive at the instantly claimed invention. This is unpersuasive because, as explained in the paragraphs above, the motivation to combine the prior art references with a reasonable expectation of success is not based on the similarity of the proteins taught therein.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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/ALEKSANDAR RADOSAVLJEVIC/Examiner, Art Unit 1662 /BRENT T PAGE/Primary Examiner, Art Unit 1663
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