DETAILED ACTION
1. The present application is being examined under the pre-AIA first to invent provisions.
Status of the Application
2. Claims 1, 3, 56, 58, 60-77, and 79-82 are pending.
3. Claims 1, 3, 56, 58, 60-77, and 80-82 are examined herein.
4. The rejection under 35 U.S.C. 112(b) is withdrawn in view of Applicant’s amendments to the claims.
Continued Examination Under 37 CFR 1.114
5. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on August 4, 2025 has been entered.
Election/Restrictions
6. In the reply filed on August 30, 2010, Applicant’s elected Group I, claims 1-8. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election was treated as an election without traverse (MPEP § 818.01(a)). The elected Group was drawn to a method of producing a transgenic plant having increased biomass accumulation (see Claims filed on August 30, 2010).
In the instant amendments, Applicant added new claims 79-82. Claim 79 is an independent claim that is drawn to a method of increasing total seed yield comprising “targeting an endogenous FVE nucleic acid in a plant.” In the Restriction Requirement issued on March 5, 2010, claim 79 would have been included in a separate group, Group IV, as being directed to a method having distinct method steps from those of the invention of Group I. It would have been also distinct from the products of Groups II and III. Consequently, claim 79 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on August 30, 2010.
However, new claims 80-82 depend in the alternative from claims 1, 3, or 79 and are examined herein to the extent that they depend from claims 1 and 3.
Claim Rejections - 35 USC § 112 - New Matter
7. 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.
8. Claims 80-82 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.
In the instant amendments, Applicant added new claims 80-82, which recite the following ranges for “total seed yield” - “at least 10%,” “at least 20%,” and “between 20 and 50%.” These recitations are New Matter.
Applicant cites Examples 2 and 8 for written support for said new claims (page 7 of the Remarks). Yet, neither those Examples nor any other portions of the disclosure, such as the originally filed claims, provide sufficient support, for the following reasons.
Example 2 teaches the yield of an fve-b10 mutant and not that of a plant expressing an inhibitory RNA. Example 8 addresses seed yield in two instances. On page 54, regarding the results in the Arabidopsis plants expressing a 35S-fve-b10 dominant negative construct, it states: “The seed yield varied from WT levels to 13% greater than that of controls. In the second instance, on page 57, addressing the expression of the 35S-HP-AtFVE-S2 construct in Arabidopsis, the specification teaches that “The seed yield was increased in transgenic lines up to 30% over the controls and the harvest index was reduced accordingly.” Neither of these teachings provides sufficient written support for the newly added claims, particularly given that the ranges in claims 80 and 81 have no upper limit, due to the term “at least;” and the fact that “between 20% and 50%” far exceeds “up to 30%.” For these reasons, the claims contain New Matter.
Claim Rejections - 35 USC § 112 - Fourth Paragraph
9. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
10. Claims 80-82 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
The claims are drawn to the methods of claims 1 or 3, “wherein the method increases total seed yield” by “at least 10%,” “at least 20%,” or “between 20% and 50%” compared to the control plant. The active steps of the methods recite introducing the inhibitory RNA into a plant or cell and growing the resultant transgenic plant. The seed yield is not recited as part of said steps but as a desired result of the method. The dependent claims thus attempt to limit said desired result and not the active method steps. For this reason, the dependent claims fail to properly further limit the subject matter of the base claims.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Interpretation
11. For the purpose of the examination, the phrases “increasing total seed yield (g/plant)” and “increased total seed yield (g/plant),” in claims 1 and 3, are given their broadest reasonable interpretation as encompassing encompass any degree of increase relative to a control plant, however small. The Examiner maintains that similar to the previously recited “weight of seed per plant,” the instant limitation is not recited in an active step and is reasonably interpreted as a desired outcome of the method. See MPEP 2111.04.
With regard to the DNA of SEQ ID NO: 3 or 206, the Examiner notes that the claims do not require the use of full-length SEQ ID NO: 3 or 206, but would encompass any complement of those sequences, wherein the expression of said complement inhibits the expression of the mRNA encoded by SEQ ID NO: 3 or 206.
The Examiner maintains that regardless of the specific phrasing that recites the property of seed yield, the active steps of the claimed method would have been made obvious by the teachings of the same cited art that made obvious the invention when the claims recited “biomass accumulation” instead of “seed yield.” For this additional reason, the “wherein” and “thereby” clauses, in claims 1 and 3, containing the term “total seed yield” are reasonably interpreted as expressing the intended result of the process steps positively recited. Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). MPEP 2114.04. It is noted that “The fact that [Applicant] has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Claim Rejections - 35 USC § 103
12. The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
13. Claims 1, 3, 56, 58, and 60-77 remain and claims 80-82 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Ausin et al (Nature (2004) 36:162-166), in view of GenBank Accession Number AY081447 (submitted on April 14, 2002), Van Nocker et al (US Patent Publication 2004/0033607), and Salehi et al (J. of Plant Physiology (2005) 162:711-717). The rejection has been modified in view of Applicant’s amendments to the claims. Applicant’s arguments submitted on August 4, 2025 were fully considered but they are not persuasive.
The claims are drawn to a method of increasing “total seed yield (g/plant) in a plant,” comprising introducing into a plant cell a nucleic acid construct that comprises a constitutive promotor operably linked a polynucleotide complementary to SEQ ID NO: 3 or 206.
Ausin et al teach cloning the genomic sequence encoding the Arabidopsis AtMSI4 protein and identifying the sequence as “FVE” because it carried the known fve mutations (Abstract; pg. 163, right col.). Ausin et al teach the phenotypes of the fve mutants and teach that the mutations showed delayed flowering and had more leaves under either long-day or short-day photoperiods (Fig. 1; pg. 163, left col.). Ausin et al teach that the fve mutations caused an increase in the steady state of the transcript of the gene called FLC, whose expression has been known to be associated with the delay in flowering (beginning on pg. 162, right col. through pg. 163, right col.). Ausin et al teach that the FVE protein comprises six WD repeat domains, and a stretch of basic residues (amino acids 20-30 of the total of 507) that resemble a nuclear localization signal (pg. 163, right col.). Ausin et al teach that lowering the level of the endogenous FVE transcript and protein via co-suppression resulted in the phenotype similar to that of the fve mutants (pg. 164, left col.). Ausin et al teach using the 35S promoter in their overexpression constructs (pg. 165, right col.).
Ausin et al do not expressly teach using a polynucleotide complementary to SEQ ID NO: 3 or 206 to suppress the expression of the FVE gene.
GenBank Accession Number AY081447 teaches a nucleic acid sequence having 100% sequence identity to the instant SEQ ID NO: 3 and the also teaches the AtMSI4 protein it encodes. GenBank Accession Number AY081447 expressly identifies the protein as an Arabidopsis putative WD-40 repeat protein called “MSI4.” The database entry and sequence alignment with the instant SEQ ID NO: 3 is set forth below.
AY081447
LOCUS AY081447 1625 bp mRNA linear PLN 14-APR-2002
DEFINITION Arabidopsis thaliana putative WD-40 repeat protein, MSI4
(At2g19520) mRNA, complete cds.
ACCESSION AY081447
VERSION AY081447.1 GI:20148236
KEYWORDS FLI_CDNA.
SOURCE Arabidopsis thaliana (thale cress)
ORGANISM Arabidopsis thaliana
Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
Spermatophyta; Magnoliophyta; eudicotyledons; Gunneridae;
Pentapetalae; rosids; malvids; Brassicales; Brassicaceae;
Camelineae; Arabidopsis.
REFERENCE 1 (bases 1 to 1625)
AUTHORS Southwick,A., Karlin-Neumann,G., Nguyen,M., Lam,B., Miranda,M.,
Palm,C.J., Bowser,L., Jones,T., Banh,J., Carninci,P., Chen,H.,
Cheuk,R., Chung,M.K., Hayashizaki,Y., Ishida,J., Kamiya,A.,
Kawai,J., Kim,C., Lin,J., Liu,S.X., Narusaka,M., Pham,P.K.,
Sakano,H., Sakurai,T., Satou,M., Seki,M., Shinn,P., Yamada,K.,
Shinozaki,K., Ecker,J., Theologis,A. and Davis,R.W.
TITLE Direct Submission
JOURNAL Submitted (27-FEB-2002) DNA Sequencing and Technology Center,
Stanford University, 855 California Avenue, Palo Alto, CA 94304,
USA
COMMENT comment 'e-mail for correspondence: arab@sequence.stanford.edu
RIKEN Genomic Sciences Center (GSC) members carried out the
collection and clustering of RAFL cDNAs (RAFL cDNA : 'RIKEN
Arabidopsis Full-Length cDNA'): Seki,M., Narusaka,M., Ishida,J.,
Satou,M., Kamiya,A., Sakurai,T., Carninci,P., Kawai,J.,
Hayashizaki,Y. and Shinozaki,K.
The Salk, Stanford, PGEC (SSP) Consortium members carried out the
sequencing and annotation of the RAFL cDNAs: Nguyen,M.,
Southwick,A., Karlin-Neumann,G., Lam,B., Miranda,M., Palm,C.J.,
Bowser,L., Jones,T., Banh,J., Chen,H., Cheuk,R., Chung,M.K.,
Kim,C., Lin,J., Liu,S.X., Pham,P.K., Sakano,H., Shinn,P.,
Yamada,K., Ecker,J., Theologis,A. and Davis,R.W.
Nguyen,M, (SSP/Stanford) and Seki,M. (RIKEN GSC) contributed
equally to this work. Shinozaki,K. (RIKEN GSC) and Davis,R.W.
(SSP/Stanford) contributed equally to this work as PIs.
FEATURES Location/Qualifiers
source 1..1625
/organism="Arabidopsis thaliana"
/mol_type="mRNA"
/db_xref="taxon:3702"
/chromosome="2"
/clone="U15529"
/ecotype="Columbia"
/note="This clone is in pENTR/SD-dTopo This is a cloned
PCR product using RIKEN clone RAFL04-16-C24 (AY059799) as
a template"
gene 1..1625
/gene="At2g19520"
/gene_synonym="F3P11.12"
CDS 1..1524
/gene="At2g19520"
/gene_synonym="F3P11.12"
/codon_start=1
/product="putative WD-40 repeat protein, MSI4"
/protein_id="AAM10009.1"
/db_xref="GI:20148237"
/translation="MESDEAAAVSPQATTPSGGTGASGPKKRGRKPKTKEDSQTPSSQ
QQSDVKMKESGKKTQQSPSVDEKYSQWKGLVPILYDWLANHNLVWPSLSCRWGPQLEQ
ATYKNRQRLYLSEQTDGSVPNTLVIANCEVVKPRVAAAEHISQFNEEARSPFVKKYKT
IIHPGEVNRIRELPQNSKIVATHTDSPDVLIWDVETQPNRHAVLGAANSRPDLILTGH
QDNAEFALAMCPTEPFVLSGGKDKSVVLWSIQDHITTIGTDSKSSGSIIKQTGEGTDK
NESPTVGPRGVYHGHEDTVEDVAFSPTSAQEFCSVGDDSCLILWDARTGTNPVTKVEK
AHDADLHCVDWNPHDDNLILTGSADNTVRLFDRRKLTANGVGSPIYKFEGHKAAVLCV
QWSPDKSSVFGSSAEDGLLNIWDYDRVSKKSDRAAKSPAGLFFQHAGHRDKVVDFHWN
ASDPWTIVSVSDDCETTGGGGTLQIWRMSDLIYRPEEEVVAELEKFKSHVMTCASKP"
Query Match 100.0%; Score 1524; DB 98; Length 1625;
Best Local Similarity 100.0%;
Matches 1524; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ATGGAGAGCGACGAAGCAGCAGCAGTGTCTCCTCAAGCAACGACACCGAGCGGAGGAACC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ATGGAGAGCGACGAAGCAGCAGCAGTGTCTCCTCAAGCAACGACACCGAGCGGAGGAACC 60
Qy 61 GGAGCTTCTGGGCCGAAGAAGAGAGGTCGGAAACCTAAAACCAAGGAAGATTCTCAGACG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GGAGCTTCTGGGCCGAAGAAGAGAGGTCGGAAACCTAAAACCAAGGAAGATTCTCAGACG 120
Qy 121 CCGTCGTCTCAGCAACAGAGCGATGTTAAAATGAAAGAAAGTGGGAAGAAAACGCAGCAG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 CCGTCGTCTCAGCAACAGAGCGATGTTAAAATGAAAGAAAGTGGGAAGAAAACGCAGCAG 180
Qy 181 TCGCCGAGTGTTGACGAGAAGTACTCTCAGTGGAAAGGTCTCGTCCCCATTCTCTACGAC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 TCGCCGAGTGTTGACGAGAAGTACTCTCAGTGGAAAGGTCTCGTCCCCATTCTCTACGAC 240
Qy 241 TGGCTCGCTAACCATAACCTCGTCTGGCCTTCACTCTCTTGCAGATGGGGTCCGCAGCTT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TGGCTCGCTAACCATAACCTCGTCTGGCCTTCACTCTCTTGCAGATGGGGTCCGCAGCTT 300
Qy 301 GAGCAAGCAACCTACAAGAATCGCCAGCGTCTGTACCTCTCAGAGCAAACTGATGGAAGT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GAGCAAGCAACCTACAAGAATCGCCAGCGTCTGTACCTCTCAGAGCAAACTGATGGAAGT 360
Qy 361 GTGCCCAATACTTTGGTCATAGCAAATTGTGAAGTTGTTAAGCCAAGGGTTGCTGCAGCA 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GTGCCCAATACTTTGGTCATAGCAAATTGTGAAGTTGTTAAGCCAAGGGTTGCTGCAGCA 420
Qy 421 GAGCACATTTCTCAGTTCAATGAAGAAGCACGTTCTCCATTTGTGAAGAAGTACAAGACC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 GAGCACATTTCTCAGTTCAATGAAGAAGCACGTTCTCCATTTGTGAAGAAGTACAAGACC 480
Qy 481 ATCATTCACCCTGGAGAGGTTAACAGAATCAGGGAACTCCCACAGAATAGTAAGATTGTT 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 ATCATTCACCCTGGAGAGGTTAACAGAATCAGGGAACTCCCACAGAATAGTAAGATTGTT 540
Qy 541 GCTACTCACACCGACAGTCCTGATGTTCTCATTTGGGATGTTGAAACCCAACCAAACCGT 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 GCTACTCACACCGACAGTCCTGATGTTCTCATTTGGGATGTTGAAACCCAACCAAACCGT 600
Qy 601 CATGCTGTGCTTGGAGCTGCAAATTCCCGTCCAGATTTGATACTAACTGGGCACCAAGAT 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 CATGCTGTGCTTGGAGCTGCAAATTCCCGTCCAGATTTGATACTAACTGGGCACCAAGAT 660
Qy 661 AATGCTGAATTTGCTCTTGCCATGTGCCCAACGGAACCCTTTGTGCTCTCCGGAGGCAAG 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 AATGCTGAATTTGCTCTTGCCATGTGCCCAACGGAACCCTTTGTGCTCTCCGGAGGCAAG 720
Qy 721 GACAAGTCAGTTGTTTTGTGGAGTATCCAAGATCACATCACAACGATTGGGACAGATTCC 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 GACAAGTCAGTTGTTTTGTGGAGTATCCAAGATCACATCACAACGATTGGGACAGATTCC 780
Qy 781 AAATCATCTGGATCTATCATCAAACAGACTGGTGAAGGTACTGATAAGAATGAGAGTCCT 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 AAATCATCTGGATCTATCATCAAACAGACTGGTGAAGGTACTGATAAGAATGAGAGTCCT 840
Qy 841 ACTGTTGGCCCACGAGGTGTATATCATGGCCATGAAGATACAGTTGAAGATGTGGCATTC 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 ACTGTTGGCCCACGAGGTGTATATCATGGCCATGAAGATACAGTTGAAGATGTGGCATTC 900
Qy 901 AGCCCGACGAGTGCACAAGAATTCTGCAGTGTTGGTGATGATTCTTGCCTTATACTATGG 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 AGCCCGACGAGTGCACAAGAATTCTGCAGTGTTGGTGATGATTCTTGCCTTATACTATGG 960
Qy 961 GATGCGAGAACTGGCACAAACCCTGTCACGAAGGTTGAAAAAGCGCATGATGCTGATCTT 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 GATGCGAGAACTGGCACAAACCCTGTCACGAAGGTTGAAAAAGCGCATGATGCTGATCTT 1020
Qy 1021 CATTGTGTTGATTGGAATCCTCATGACGACAATCTGATCCTGACAGGGTCAGCAGACAAC 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 CATTGTGTTGATTGGAATCCTCATGACGACAATCTGATCCTGACAGGGTCAGCAGACAAC 1080
Qy 1081 ACTGTCCGGTTGTTTGATCGTAGGAAGCTTACCGCTAATGGAGTTGGTTCGCCTATTTAC 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 ACTGTCCGGTTGTTTGATCGTAGGAAGCTTACCGCTAATGGAGTTGGTTCGCCTATTTAC 1140
Qy 1141 AAATTTGAGGGACACAAAGCTGCTGTTCTTTGTGTTCAGTGGTCTCCTGATAAGTCATCC 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 AAATTTGAGGGACACAAAGCTGCTGTTCTTTGTGTTCAGTGGTCTCCTGATAAGTCATCC 1200
Qy 1201 GTCTTTGGGAGCTCTGCAGAAGATGGTCTCTTGAACATCTGGGATTATGACAGGGTCAGT 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 GTCTTTGGGAGCTCTGCAGAAGATGGTCTCTTGAACATCTGGGATTATGACAGGGTCAGT 1260
Qy 1261 AAGAAGTCTGATCGTGCAGCTAAAAGCCCCGCTGGGCTCTTCTTCCAGCATGCTGGTCAC 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 AAGAAGTCTGATCGTGCAGCTAAAAGCCCCGCTGGGCTCTTCTTCCAGCATGCTGGTCAC 1320
Qy 1321 AGGGACAAAGTTGTTGATTTCCACTGGAATGCTTCAGACCCTTGGACTATTGTCAGTGTT 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 AGGGACAAAGTTGTTGATTTCCACTGGAATGCTTCAGACCCTTGGACTATTGTCAGTGTT 1380
Qy 1381 TCTGATGACTGTGAGACTACTGGTGGAGGTGGAACATTGCAGATATGGCGGATGAGTGAC 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 TCTGATGACTGTGAGACTACTGGTGGAGGTGGAACATTGCAGATATGGCGGATGAGTGAC 1440
Qy 1441 TTGATTTACAGACCAGAAGAAGAAGTCGTGGCAGAATTGGAGAAGTTCAAGTCGCATGTT 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 TTGATTTACAGACCAGAAGAAGAAGTCGTGGCAGAATTGGAGAAGTTCAAGTCGCATGTT 1500
Qy 1501 ATGACTTGTGCCTCCAAGCCTTAA 1524
||||||||||||||||||||||||
Db 1501 ATGACTTGTGCCTCCAAGCCTTAA 1524
The instant SEQ ID NO's 57, 87, 140, 118, 174, and 277 represent portions of SEQ ID NO: 3 and have 100% sequence identity to the sequence of GenBank Accession Number AY081447 (see Sequence Listing on pg. 8 and 9 of the Specification; and see Sequence Search Results for SEQ ID NO: 57, 87, 140, 118, 174, and 277 against published applications).
The nucleic acid sequence of GenBank Accession Number AY081447 has 80.9% sequence identity to the instant SEQ ID NO: 206. The sequence alignment is set forth below.
AY081447
LOCUS AY081447 1625 bp mRNA linear PLN 14-APR-2002
DEFINITION Arabidopsis thaliana putative WD-40 repeat protein, MSI4
(At2g19520) mRNA, complete cds.
ACCESSION AY081447
VERSION AY081447.1 GI:20148236
KEYWORDS FLI_CDNA.
SOURCE Arabidopsis thaliana (thale cress)
ORGANISM Arabidopsis thaliana
Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
Spermatophyta; Magnoliophyta; eudicotyledons; Gunneridae;
Pentapetalae; rosids; malvids; Brassicales; Brassicaceae;
Camelineae; Arabidopsis.
REFERENCE 1 (bases 1 to 1625)
AUTHORS Southwick,A., Karlin-Neumann,G., Nguyen,M., Lam,B., Miranda,M.,
Palm,C.J., Bowser,L., Jones,T., Banh,J., Carninci,P., Chen,H.,
Cheuk,R., Chung,M.K., Hayashizaki,Y., Ishida,J., Kamiya,A.,
Kawai,J., Kim,C., Lin,J., Liu,S.X., Narusaka,M., Pham,P.K.,
Sakano,H., Sakurai,T., Satou,M., Seki,M., Shinn,P., Yamada,K.,
Shinozaki,K., Ecker,J., Theologis,A. and Davis,R.W.
TITLE Direct Submission
JOURNAL Submitted (27-FEB-2002) DNA Sequencing and Technology Center,
Stanford University, 855 California Avenue, Palo Alto, CA 94304,
USA
COMMENT comment 'e-mail for correspondence: arab@sequence.stanford.edu
RIKEN Genomic Sciences Center (GSC) members carried out the
collection and clustering of RAFL cDNAs (RAFL cDNA : 'RIKEN
Arabidopsis Full-Length cDNA'): Seki,M., Narusaka,M., Ishida,J.,
Satou,M., Kamiya,A., Sakurai,T., Carninci,P., Kawai,J.,
Hayashizaki,Y. and Shinozaki,K.
The Salk, Stanford, PGEC (SSP) Consortium members carried out the
sequencing and annotation of the RAFL cDNAs: Nguyen,M.,
Southwick,A., Karlin-Neumann,G., Lam,B., Miranda,M., Palm,C.J.,
Bowser,L., Jones,T., Banh,J., Chen,H., Cheuk,R., Chung,M.K.,
Kim,C., Lin,J., Liu,S.X., Pham,P.K., Sakano,H., Shinn,P.,
Yamada,K., Ecker,J., Theologis,A. and Davis,R.W.
Nguyen,M, (SSP/Stanford) and Seki,M. (RIKEN GSC) contributed
equally to this work. Shinozaki,K. (RIKEN GSC) and Davis,R.W.
(SSP/Stanford) contributed equally to this work as PIs.
FEATURES Location/Qualifiers
source 1..1625
/organism="Arabidopsis thaliana"
/mol_type="mRNA"
/db_xref="taxon:3702"
/chromosome="2"
/clone="U15529"
/ecotype="Columbia"
/note="This clone is in pENTR/SD-dTopo This is a cloned
PCR product using RIKEN clone RAFL04-16-C24 (AY059799) as
a template"
gene 1..1625
/gene="At2g19520"
/gene_synonym="F3P11.12"
CDS 1..1524
/gene="At2g19520"
/gene_synonym="F3P11.12"
/codon_start=1
/product="putative WD-40 repeat protein, MSI4"
/protein_id="AAM10009.1"
/db_xref="GI:20148237"
/translation="MESDEAAAVSPQATTPSGGTGASGPKKRGRKPKTKEDSQTPSSQ
QQSDVKMKESGKKTQQSPSVDEKYSQWKGLVPILYDWLANHNLVWPSLSCRWGPQLEQ
ATYKNRQRLYLSEQTDGSVPNTLVIANCEVVKPRVAAAEHISQFNEEARSPFVKKYKT
IIHPGEVNRIRELPQNSKIVATHTDSPDVLIWDVETQPNRHAVLGAANSRPDLILTGH
QDNAEFALAMCPTEPFVLSGGKDKSVVLWSIQDHITTIGTDSKSSGSIIKQTGEGTDK
NESPTVGPRGVYHGHEDTVEDVAFSPTSAQEFCSVGDDSCLILWDARTGTNPVTKVEK
AHDADLHCVDWNPHDDNLILTGSADNTVRLFDRRKLTANGVGSPIYKFEGHKAAVLCV
QWSPDKSSVFGSSAEDGLLNIWDYDRVSKKSDRAAKSPAGLFFQHAGHRDKVVDFHWN
ASDPWTIVSVSDDCETTGGGGTLQIWRMSDLIYRPEEEVVAELEKFKSHVMTCASKP"
Query Match 80.9%; Score 1232.8; DB 98; Length 1625;
Best Local Similarity 89.3%;
Matches 1366; Conservative 0; Mismatches 152; Indels 12; Gaps 3;
Qy 1 ATGGAGAGCGACGGAGCGGCAGCGG------CAGGAGCAGCGTCGCCGAGCGGAGGAAAC 54
||||||||||||| ||| ||||| | | |||| || | ||||||||||||| |
Db 1 ATGGAGAGCGACGAAGCAGCAGCAGTGTCTCCTCAAGCAACGACACCGAGCGGAGGAACC 60
Qy 55 GTGACACCGGCGCCGAAGAAGAGAGGACGGAAACCAAAGAGCAAGGACGAGTCTCAGACG 114
| | | | ||||||||||||||| |||||||| || | |||||| || |||||||||
Db 61 GGAGCTTCTGGGCCGAAGAAGAGAGGTCGGAAACCTAAAACCAAGGAAGATTCTCAGACG 120
Qy 115 CAGCAGGAGCAGGAGGAAAGGGGTGGGAAAATGAAGGAAAGCGGGAAGAAAACGAAGCAG 174
| | | ||| | | || | || |||||||| ||||| |||||||||||| ||||
Db 121 CCGTCGTCTCAGCAACAGAGCGATGTTAAAATGAAAGAAAGTGGGAAGAAAACGCAGCA- 179
Qy 175 GGGGAGCAGAGCGTGGACGAGAAGTACACTCAGTGGAAAGGTCTCGTCCCCATCCTCTAC 234
| || ||| || |||||||||||| ||||||||||||||||||||||||| ||||||
Db 180 --GTCGCCGAGTGTTGACGAGAAGTACTCTCAGTGGAAAGGTCTCGTCCCCATTCTCTAC 237
Qy 235 GACTGGCTCGCCAATCACAACCTCGTCTGGCCTTCCCTCTCTTGCAGATGGGGTCCACAG 294
||||||||||| || || ||||||||||||||||| |||||||||||||||||||| |||
Db 238 GACTGGCTCGCTAACCATAACCTCGTCTGGCCTTCACTCTCTTGCAGATGGGGTCCGCAG 297
Qy 295 ATCGAACAAGCAACCTACAAGAATCGACAGCGTCTTTACCTCTCAGAACAAACTGATGGC 354
| || |||||||||||||||||||| |||||||| ||||||||||| |||||||||||
Db 298 CTTGAGCAAGCAACCTACAAGAATCGCCAGCGTCTGTACCTCTCAGAGCAAACTGATGGA 357
Qy 355 AGTGTGCCCAACACTCTAGTCATAGCGAATTGCGAAGTTGTTAAGCCAAGGGTCGCTGCA 414
||||||||||| ||| | |||||||| ||||| |||||||||||||||||||| ||||||
Db 358 AGTGTGCCCAATACTTTGGTCATAGCAAATTGTGAAGTTGTTAAGCCAAGGGTTGCTGCA 417
Qy 415 GCAGAGCACATATCTCAGTTCAACGAAGAAGCACGTTCTCCATTTGTGAAGAAGTTCAAG 474
||||||||||| ||||||||||| ||||||||||||||||||||||||||||||| ||||
Db 418 GCAGAGCACATTTCTCAGTTCAATGAAGAAGCACGTTCTCCATTTGTGAAGAAGTACAAG 477
Qy 475 ACCATCATTCACCCTGGAGAGGTTAACCGAATCAGGGAACTCCCACAAAACAGTAAGATT 534
||||||||||||||||||||||||||| ||||||||||||||||||| || |||||||||
Db 478 ACCATCATTCACCCTGGAGAGGTTAACAGAATCAGGGAACTCCCACAGAATAGTAAGATT 537
Qy 535 ATTGCTACTCACACCGACAGTCCTGATGTTCTCATTTGGGATGTTGAAACCCAACCAAAC 594
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 538 GTTGCTACTCACACCGACAGTCCTGATGTTCTCATTTGGGATGTTGAAACCCAACCAAAC 597
Qy 595 CGTCATGCTGTCCTTGGAGCTGCACATTCCCGTCCTGATTTGGTATTAACTGGACATCAA 654
||||||||||| |||||||||||| |||||||||| |||||| || ||||||| || |||
Db 598 CGTCATGCTGTGCTTGGAGCTGCAAATTCCCGTCCAGATTTGATACTAACTGGGCACCAA 657
Qy 655 GACAATGCTGAATTCGCTCTTGCAATGTGCCCAACCGAACCCTTTGTCCTCTCTGGAGGC 714
|| ||||||||||| |||||||| ||||||||||| ||||||||||| ||||| ||||||
Db 658 GATAATGCTGAATTTGCTCTTGCCATGTGCCCAACGGAACCCTTTGTGCTCTCCGGAGGC 717
Qy 715 AAAGACAAGTCAGTTGTTTTGTGGAGTATCCAGGACCACATCACAACCGCTGGTAGTACA 774
|| ||||||||||||||||||||||||||||| || ||||||||||| ||| |||
Db 718 AAGGACAAGTCAGTTGTTTTGTGGAGTATCCAAGATCACATCACAACGATTGGG---ACA 774
Qy 775 GACTCCAAATCATCTGGATCCATCATCAAACAGACTGGTGAAGGTGGTGATAAGACTGAG 834
|| ||||||||||||||||| |||||||||||||||||||||||| |||||||| ||||
Db 775 GATTCCAAATCATCTGGATCTATCATCAAACAGACTGGTGAAGGTACTGATAAGAATGAG 834
Qy 835 AGTCCTTCTCTTGGCCCGCGAGGTGTATATCATGGCCATGATGATACCGTTGAAGATGTC 894
|||||| || ||||||| ||||||||||||||||||||||| ||||| |||||||||||
Db 835 AGTCCTACTGTTGGCCCACGAGGTGTATATCATGGCCATGAAGATACAGTTGAAGATGTG 894
Qy 895 GCTTTCAGCCCCACTAGTGCACAAGAGTTCTGCAGTGTCGGTGACGATTCTTGCCTTATA 954
|| |||||||| || ||||||||||| ||||||||||| ||||| |||||||||||||||
Db 895 GCATTCAGCCCGACGAGTGCACAAGAATTCTGCAGTGTTGGTGATGATTCTTGCCTTATA 954
Qy 955 CTATGGGATGCAAGAACAGGCACTAGCCCTGTCACGAAGGTTGAAAAGGCGCACGATGCT 1014
||||||||||| ||||| ||||| | ||||||||||||||||||||| ||||| ||||||
Db 955 CTATGGGATGCGAGAACTGGCACAAACCCTGTCACGAAGGTTGAAAAAGCGCATGATGCT 1014
Qy 1015 GATCTTCATTGTGTCGATTGGAACCCTCATGATGACAATCTGATCCTGACAGGGTCTGCA 1074
|||||||||||||| |||||||| |||||||| ||||||||||||||||||||||| |||
Db 1015 GATCTTCATTGTGTTGATTGGAATCCTCATGACGACAATCTGATCCTGACAGGGTCAGCA 1074
Qy 1075 GACAACACTGTTCGGTTGTATGATCGTAGGAAACTAACCTCAAATGGAGTGGGTACGCCT 1134
||||||||||| ||||||| |||||||||||| || ||| | |||||||| ||| |||||
Db 1075 GACAACACTGTCCGGTTGTTTGATCGTAGGAAGCTTACCGCTAATGGAGTTGGTTCGCCT 1134
Qy 1135 ATTTACAAATTTGAAGGCCACAAAGCTGCTGTTCTTTGCGTTCAGTGGTCTCCTGATAAG 1194
|||||||||||||| || |||||||||||||||||||| |||||||||||||||||||||
Db 1135 ATTTACAAATTTGAGGGACACAAAGCTGCTGTTCTTTGTGTTCAGTGGTCTCCTGATAAG 1194
Qy 1195 TCATCTGTTTTTGGGAGTTCCGCGGAAGATGGTCTCTTGAACATCTGGGATTATGACAGG 1254
||||| || |||||||| || || ||||||||||||||||||||||||||||||||||||
Db 1195 TCATCCGTCTTTGGGAGCTCTGCAGAAGATGGTCTCTTGAACATCTGGGATTATGACAGG 1254
Qy 1255 GTCAGTAAGAAGTCTGATCGTGCAGCTAAAAGTCCGGCTGGTCTCTTCTTCCAGCATGCT 1314
|||||||||||||||||||||||||||||||| || ||||| ||||||||||||||||||
Db 1255 GTCAGTAAGAAGTCTGATCGTGCAGCTAAAAGCCCCGCTGGGCTCTTCTTCCAGCATGCT 1314
Qy 1315 GGTCACAGGGACAAAGTTGTTGATTTCCACTGGAATGCAGAGGACCCTTGGACTATTGTC 1374
|||||||||||||||||||||||||||||||||||||| ||||||||||||||||||
Db 1315 GGTCACAGGGACAAAGTTGTTGATTTCCACTGGAATGCTTCAGACCCTTGGACTATTGTC 1374
Qy 1375 AGTGTTTCTGATGACTGCGAGACTACTGGTGGAGGTGGAACACTGCAGATATGGCGGATG 1434
||||||||||||||||| |||||||||||||||||||||||| |||||||||||||||||
Db 1375 AGTGTTTCTGATGACTGTGAGACTACTGGTGGAGGTGGAACATTGCAGATATGGCGGATG 1434
Qy 1435 AGTGACTTGATTTACAGACCGGAGGAGGAAGTTCTGGCAGAGTTGGAGAAGTTCAAGTCG 1494
|||||||||||||||||||| || || ||||| ||||||| ||||||||||||||||||
Db 1435 AGTGACTTGATTTACAGACCAGAAGAAGAAGTCGTGGCAGAATTGGAGAAGTTCAAGTCG 1494
Qy 1495 CATGTTATGACATGTGCCTCCAAGCCTTGA 1524
||||||||||| |||||||||||||||| |
Db 1495 CATGTTATGACTTGTGCCTCCAAGCCTTAA 1524
Instant SEQ ID NO: 317 (claim 65) has 85% identity to the region comprising nucleotides 1136-1245 of the GenBank Accession Number AY081447. Sequence alignment is set forth below.
Score
Expect
Identities
Gaps
Strand
Frame
122 bits(134)
3e-32()
93/110(85%)
0/110(0%)
Plus/Plus
Features:
Query 1136 TTTACAAATTTGAGGGACACAAAGCTGCTGTTCTTTGTGTTCAGTGGTCTCCTGATAAGT 1195
|| ||||||||||||| || ||||||||||||||||||||||||||||| ||||| |||
Sbjct 11 TTCACAAATTTGAGGGTCATAAAGCTGCTGTTCTTTGTGTTCAGTGGTCACCTGACAAGG 70
Query 1196 CATCCGTCTTTGGGAGCTCTGCAGAAGATGGTCTCTTGAACATCTGGGAT 1245
|||| || ||||| |||||||| ||||| || |||| || | ||||||
Sbjct 71 CATCTGTATTTGGAAGCTCTGCGGAAGACGGCTTCTTAAATGTGTGGGAT 120
Instant SEQ ID NO: 351 (claim 66) 94% sequence identity to the region comprising nucleotides 1288-1431 of GEN Bank Accession Number AY081447. The sequence alignment is set forth below.
Score
Expect
Identities
Gaps
Strand
Frame
224 bits(248)
4e-63()
136/144(94%)
0/144(0%)
Plus/Plus
Features:
Query 1288 CCCGCTGGGCTCTTCTTCCAGCATGCTGGTCACAGGGACAAAGTTGTTGATTTCCACTGG 1347
|| ||||| |||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1 CCGGCTGGTCTCTTCTTCCAGCATGCTGGTCACAGGGACAAAGTTGTTGATTTCCACTGG 60
Query 1348 AATGCTTCAGACCCTTGGACTATTGTCAGTGTTTCTGATGACTGTGAGACTACTGGTGGA 1407
||||| ||||||||||||||||||||||||||||||||||| |||||||||||||||
Sbjct 61 AATGCAGAGGACCCTTGGACTATTGTCAGTGTTTCTGATGACTGCGAGACTACTGGTGGA 120
Query 1408 GGTGGAACATTGCAGATATGGCGG 1431
||||||||| ||||||||||||||
Sbjct 121 GGTGGAACACTGCAGATATGGCGG 144
Van Nocker et al teach methods and constructs to regulate plant genes that regulate flowering. Van Nocker et al teach using antisense expression vectors targeting the gene involved in flowering regulation; and transgenic plants comprising said expression vectors (Abstract; paragraphs 0011-0014 and 0017; 0120). Van Nocker et al teach using RNAi techniques for gene silencing, including siRNA constructs that are complementary to the target nucleic acid and comprise a duplex that is 18-25 nucleotides long (paragraph 0122). Van Nocker et al teach that an effective method to downregulate a gene is by hairpin RNA constructs (paragraph 0271). Van Nocker teach applying the method of their invention to a number of plant species, including Arabidopsis, rice, corn, and Brassica (paragraph 0275). Van Nocker et al teach transforming plant material with the constructs of their invention, and after selecting for the material that expresses the gene of interest, regenerating whole plants (paragraph 0300). Van Nocker et al teach using the 35S promoter in their expression constructs (paragraph 0291, for example).
Van Nocker et al teach that the decreased expression or mutation of the gene of their invention, called “VIP” affects the expression of FLC (paragraphs 0009 and 0042). Van Nocker et al teach that FLC is known to be regulated by FVE (paragraph 0141). Van Nocker et al teach that in ornamental foliage plants and in agronomically important plants that are grown for their leaf tissue, such as spinach and lettuce, it is highly desirable to suppress flowering as long as possible (paragraph 0004). Van Nocker et al also teach that “in other agronomically important plants grown for their seed products, such as fruits and vegetables as diverse as beans, peas, corn, and tomatoes, decreasing or increasing the time to flowering might expand the range where these crops could be grown, and might allow more precise control of nutrient flow to the crop” (paragraph 0004).
Salehi et al teach overexpressing FLC to produce the delay in flowering (Abstract; page 712, left col.). Salehi et al teach that “The delay in flowering resulted in higher biomass yield in all the transgenic lines that was significantly different from control. The higher biomass yield would be useful for efficient production of tobacco, leafy vegetables, and biomass crops, such as switchgrass and maize” (page 716; right col.).
Salehi et al teach that in all lines overexpressing FLC, the average thousand seed weight was significantly higher than in control plants, including an increase of 53% (from 66 to 101 mg). In one line, the seed yield per plant was higher as well, wherein the increase amount to 15% (from 6.12 to 7.12 g/plant) (Table 2).
At the time the invention was made, it would have been prima facie obvious to one having ordinary skill in the art to modify the teachings of Ausin et al using the constructs and method of Van Nocker et al and obtain antisense or RNAi expression vectors (including hairpin constructs), targeting an endogenous FVE gene, and to obtain transgenic plants and seeds stably expressing said vectors. It would have been obvious to use, in said construct, a sequence complementary to a known MSI4 gene, such as that of the GenBank Accession Number AY081447, which is expressly identified as such, and which has 100% sequence identity to the instant SEQ ID NO: 3. It would have been obvious to express said sequence under the control of a constitutive promoter, such as the 35S promoter.
A specific sequence in said vector would have been a matter of design choice given that the full-length gene is known and the methods of making inhibitory constructs are known as well (see Van Nocker et al). In addition, the prima facie obvious inhibitory polynucleotides based on GenBank Accession Number AY081447 would be considered functional equivalents when used in a method comprising obtaining a plant expressing them. For example, if would have been obvious to use a sequence complementary to any of the six WD repeats, including those encompassed by GenBank Accession Number AY081447, given their conserved nature, or other motifs characterizing FVE, as taught by Ausin et al.
By transforming a plant with said construct, one would have had reasonable expectation of success that the plant would have a decreased level of the endogenous FVE expression. Based on the high degree of homology between the Arabidopsis FVE and Brassica napus, and given the conserved nature of the WD repeats, one would have a reasonable expectation of success that an RNAi or antisense construct based on the Arabidopsis sequence would predictably inhibit the FVE in other plant species, including Brassica napus.
In view of the teachings of Ausin et al, Van Nocker et al, and Salehi et al, one would have also reasonably expected that a transgenic plant in which the expression of FVE protein is inhibited would have higher biomass. In addition, given the teachings of Salehi et al, one would have also reasonably expected at least some of said plants to show increase in seed yield, wherein the yield encompasses the increase in total seed weight per plant, at least by the degree taught by Salehi et al. This is particularly so give that in the plants in which FLC was overexpressed, such as those of Salehi et al, the endogenous FVE remains active.
Moreover, since the property of increased seed yield represents a desired outcome of the active, positively recited method steps, said property would have naturally flowed from the prima facie obvious methods: “The fact that [Applicant] has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
One would have been motivated to combine said teachings, given that Ausin et al teach that suppressing the FVE expression resulted in the phenotype similar to that of the fve mutants, which included the mutant plants having more leaves, an agronomically desirable phenotype. One would have also been motivated to do so given the teachings of Van Nocker et al that suppressing flowering is highly desirable in a variety of plants. One would have been also motivated to delay flowering, in order to, specifically, obtain plants with increased biomass, or to obtain bigger seeds, or higher yield, as taught by Salehi et al.
Response to Arguments
As a preliminary matter, the Examiner notes the following with regard to the procedural history of the instant application and the term “total seed yield” recited in the claims, as instantly amended.
The term “seed yield” appeared in the claims for the first time in the amendments filed on April 26, 2022, when Applicant added it to the independent claims 1 and 3. Those claim amendments were submitted together with a request for continued examination filed after Applicant’s appeal. The issue of seed yield increase, on which Applicant’s present argument hinges, was not raised in Applicant’s briefing on appeal or anywhere in the preceding prosecution history: the claims were previously directed to a method for “increasing biomass accumulation” not “seed yield” (see, for example, the Claims filed on January 8, 2019).
Nothing in the specification indicates that the increase in seed yield in any FVE-suppressed plant would have been unexpected or that Applicant deemed it unexpected. The specification mentions seed yield in transgenic FVE-suppressed plants in two instances, both in Example 8. In the first one, on page 54, addressing the results in the Arabidopsis plants expressing the 35S-fve-b10 dominant negative construct, the specification states: “The seed yield varied from WT levels to 13% greater than that of controls.” In the second instance, on page 57, addressing the expression of the 35S-HP-AtFVE-S2 construct in Arabidopsis, the specification states: “The seed yield was increased in transgenic lines up to 30% over the controls and the harvest index was reduced accordingly.” (Example 2, to which Applicant refers on page 12 of the instant Remarks deals with the yield of the fve-b10 Arabidopsis mutant, which mutant is outside the scope of the instant invention, because the claimed methods require RNA suppression). Neither of said two teachings provides support to Applicant’s unexpected results argument regarding seed yield.
Further, on January 8, 2019, Applicant filed a Declaration of Yafan Huang, in which the Declarant, in contradiction to the express teachings of the cited prior art, argued that “there is no correlation between delayed flowering and increased biomass” (paragraph 9). The Declaration did not mention seed yield.
The fact that the issue that is now central to Applicant’s argument was not raised by Applicant or recognized by Applicant’s own experts until after the post-appeal RCE, nor taught in the specification is consistent with the Examiner’s position that any increase in seed yield observed as a result of practicing the active steps of the claimed method would not amount to a showing of unexpected results sufficient to overcome the rejection. The Examiner addresses Applicant’s individual arguments below.
Applicant argues that the claims have been amended. Applicant argues that there “is no motivation to modify or combine the cited references.” Applicant asserts that “The Office's reasoning to modify the teachings of Ausin with GenBank and Van Nocker to delay flowering, in order to, specifically, obtain plants with increased biomass, or to obtain bigger seeds, as taught by Salehi et al, is not based on logic nor sound scientific reasoning. The scientific fact is that nearly all crops (i.e., all angiosperms) must flower to produce seed. Thus, why would one skilled in the art seeking to increase seed production in a plant want to delay flowering? The answer is they would not. Rather, one skilled in the art would be looking, for example, to increase the number of flowers per plant or to increase the duration of flowering time - perhaps by encouraging earlier flowering, to produce a higher overall seed yield per plant. … Be that as it may, Applicant respectfully submits that the Office cannot forget or ignore the motivation to combine or modify the references - which still must be present in the first place to establish a prima facie case of obviousness” (pages 8-9 of the Remarks).
Applicant’s argument is not found to be persuasive. For the specific teachings of the cited art that form the premises supporting the finding of motivation, Applicant is directed to the rejection above. Applicant’s argument, however, fails to either address those teachings or adequately challenge the reasoning that leads to said finding, for the following reasons. First, Applicant’s position relies upon and requires the implied premise that one would have been motivated to arrive at the instant invention only by “seeking to increase seed production.” This is contradicted by the relevant legal precedent, as applied to the instant facts. MPEP 214(IV) explains that “the reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant” (emphasis supplied). See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006).
This means that one of ordinary skill in the art would not have been needed to be motivated by increasing total seed yield per plant in order to arrive at the active steps of the claimed methods. For example, one would have been motivated by the teachings of Ausin et al, who teach that suppressing the FVE expression results in the plants having more leaves, an agronomically desirable phenotype in many crops, all of which crops are encompassed by the claims.
Second, the term “total seed yield (g/plant)” is recited in the instant claims as an intended result of the claimed method and not as an active step thereof. The active steps of claim 1, for example, are introducing a nucleic acid construct into a plant cell, regenerating a plant from said cell, and growing the plant. The newly added “wherein” clause and the preamble, which recite said term, represent the outcome of the method. Applicant’s argument is thus directed to the intended result of the method and not the obviousness of its active steps.
Third, Salehi et al do teach an increase in seed yield per plant in one of the transformed lines, and teach an increase in seed weight in all of said lines (see Table 2). Contrary to Applicant’s position, this teaching would have actually contributed to the motivation to combine the cited art. Particularly given that Salehi et al teach the overexpression of FLC and not the suppression of FVE: in a plant overexpressing FLC (as opposed to a plant with an inactive FVE), the endogenous FVE would remain active and will continue to suppress FLC. Nothing in the prior art suggests that an increase in biomass accumulation due to FVE suppression, as observed, for example, by Ausin in the mutant Arabidopsis plants, would be incompatible with an increase in seed yield.
Applicant reiterates the argument that Salehi et al teaches away from the instant invention. Applicant cites Tadege et al, which teaches that in rice “ectopic AtFLC expression may interfere with a number of aspects of reproductive development” including, apparently, seed production, as “it was difficult to recover seeds” (pages 10-11 of the Remarks). Applicant alleges that “the cited art combined with the knowledge at the time of the invention teaches away from reducing expression of FLC to increase seed yield” (page 12).
This argument is not found to be persuasive. It is noted that when considering a teaching away argument, the nature of the teaching is highly relevant and must be weighed in substance. A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 553, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994). See In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). See also UCB, Inc. v. Actavis Labs, UT, Inc., 65 F.4th 679, 692, 2023 USPQ2d 448 (Fed. Cir. 2023) ("a reference does not teach away if it merely expresses a general preference for an alternative invention but does not criticize, discredit or otherwise discourage investigation into the invention claimed.") MPEP2145.
In the instant case, the fact that the Arabidopsis FLC had a negative effect on yield when exogenously overexpressed in rice would not have taught away from suppressing the expression of the endogenous FVE. This is particularly true with regard to the teachings of the Tadege article whose authors were unable to detect an endogenous homolog of the Arabidopsis FLC in a rice plant and speculate that it may be the case that “only a small part of the FLC protein is critical for its repressive function” (paragraph spanning pages 366 and 367). In fact, these teachings of Tadege would have provided motivation to attempt to suppress the expression of FVE, which is the repressor of FLC, as opposed to overexpressing FLC, in order to achieve any desirable phenotype associated with the known FLC activity.
With regard to the teachings of Salehi, the Examiner maintains that the fact that four of the five transformed lines in Salehi et al showed a decrease in seed yield per plant would not have taught away from the instant invention. Salehi et al do teach an increase in seed yield per plant in one of the transformed lines, and teach an increase in seed weight in all of said lines (see Table 2).
Applicant argues that “reducing the expression of FVE… would not have been expected to produce an increase total seed yield (g) per plant” (page 12 of the Remarks). Applicant argues impermissible hindsight as follows: “at the time of the invention, there were four genetic pathways that had been identified that controlled flowering time in plants. FVE was just one of at least 8 genes that were shown to act on FLC. Today, there are at least five genetic pathways that have been identified as playing a role in the timing of plant flowering, and at least 20 genes that act on FLC. Thus, scientists had only begun to scratch the surface of how these genetic pathways interacted with each other, and the environment, to control flowering. Due to the lack of evidence in the cited art, and the fact that an increased total seed yield (g/plant) resulting from reduced FVE expression is only present on the record in Applicant's specification, it logically follows that the Examiner's assertions of obviousness have been improperly gleaned from Applicant's own specification” (page 13 of the Remarks).
This is not found to be persuasive. With regard to the unexpected results, in view of the teachings of Ausin et al, Van Nocker et al, and Salehi et al, one would have reasonably expected that a transgenic plant in which the expression of FVE protein is inhibited would have higher biomass and would have expected at least some of said plants to show increase in seed yield, wherein the yield encompasses the increase in total seed weight per plant (see the rejection and the discussion above).
Regarding the impermissible hindsight, it is unclear how the statements regarding “four genetic pathways” or the fact that genes other than FVE were known to suppress FLC show said hindsight as no explanation is provided. At the same time, the teachings of Ausin et al expressly suggest that targeting the endogenous FVE results in delayed flowering and increased biomass.
Next, from the premise that “increased total seed yield (g/plant) resulting from reduced FVE expression is only present on the record in Applicant's specification” it does not “logically follow” that “assertions of obviousness have been improperly gleaned from Applicant's own specification,” as Applicant alleges. This is because the active steps of the instantly claimed method would have been prima facie obvious regardless of whether one would have known about the seed yield increase in any FVE suppressed plants.
Moreover, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, no knowledge was gleaned only from Applicant’s disclosure.
The methods recited in the instant claims aim to inhibit the expression of FVE, wherein said gene comprises the nucleic acids of SEQ ID NO: 3 or 206, using a polynucleotide complementary to said nucleic acids. SEQ ID NO: 3 is a coding sequence of the FVE gene from Arabidopsis, while SEQ ID NO: 206 is a coding sequence from Brassica napus (see pages 8-9 of the specification).
In Arabidopsis, the product of said gene, the FVE protein, is a component of a flowering-regulation signaling pathway, wherein FVE is a negative regulator of the transcription of another member of said pathway, FLC. The protein encoded by the FLC gene inhibits flowering. This relationship between FVE and FLC was known in the art at the time of invention, and is taught by Ausin et al (see Abstract of Ausin et al). Consistent with the fact that FVE is a negative regulator of the FLC expression, Ausin et al teach that the mutations of FVE resulted in the increase in the steady state level of the FLC transcript, which led to a delay in flowering (page 163, left col.). If one of ordinary skill in the art needed to suppress flowering in Arabidopsis, the teachings of Ausin et al provide a clear strategy to achieve that: maintain the expression of the FLC by disrupting its negative regulator, FVE. Given the conserved nature of FVE (see Ausin et al, Abstract), one would reasonably expect to achieve the same in other plant species as well.
One of ordinary skill in the art would readily recognize that, barring evidence to the contrary, the effects of overexpressing a native plant protein may not be the opposite of the effects of disrupting the expression of that protein in the plant. This was precisely what Ausin et al observed with FVE.
Ausin et al do not expressly teach the following limitations of the instant claims: SEQ ID NO’s, the use of complementary nucleic acids to disrupt the expression of the endogenous FVE, and the fact that delayed flowering results in the increase in seed yield or “total seed yield (g/plant) in a plant” These teachings are supplied by the GenBank Accession Number, Van Nocker et al, and Salehi et al.
Van Nocker et al teach using antisense expression vectors and siRNA constructs to suppress the expression of genes involved in flowering regulation, and teach the desirability of suppressing flowering in some agricultural plants (paragraphs 0004; 0011-0014 and 0017; 0120, 0141).
The mechanism that is at the heart of Van Nocker et al’s invention is the obverse of the claimed one: Van Nocker et al disrupt a positive upstream regulator of FLC, called “VIP,” whose suppression results in early flowering, which is desirable in some instances, just as later flowering is desirable in others (see paragraph 0009 of Van Nocker). While this teaching was not relied on by the Examiner, it is fully consistent with Ausin et al’s description of the FLC signaling pathway. And in view of the teachings of Salehi, one would reasonably expect at least some increase in yield in at least some of the plants in which the FVE expression is decreased.
Applicant is reminded that “Obviousness does not require absolute predictability of success. Indeed, for many inventions that seem quite obvious, there is no absolute predictability of success until the invention is reduced to practice. ... For obviousness under § 103, all that is required is a reasonable expectation of success” (In re O'Farrell, 853 F1894, 903-904 (Fed. Cir. 1988). The rejection is maintained.
Conclusion
14. No claims are allowed.
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/MYKOLA V. KOVALENKO/Primary Examiner, Art Unit 1662
/BRATISLAV STANKOVIC/Supervisory Patent Examiner, Art Units 1661 & 1662