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 .
Claim Status
Claims 1-2, 11-14, 16, 23, 28, 32, 34, 37, 65, 71 and 115-119 are pending.
The Applicant added new claims 115-119.
Claims 115-119 are newly added. The newly added claims depend on claims from the non-elected inventions and would read on to the non-elected invention II and invention III.
Claims 28, 32, 34, 37, 65, 71 and 115-119 are withdrawn from examination as part of non-elected inventions.
Claims 1-2, 11-14, 16 and 23 are being examined.
All previous objections and rejections not set forth below are withdrawn in view of the amendments by the Applicant.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2, 11-14, 16 and 23 remain rejected under 35 U.S.C. 103 as being unpatentable over Christensen et al. (Structure and expression of a maize phytochrome-encoding gene, 1989, Gene, 85:381-390) in view of Kohichi et al. (US7045680B2), Zhou et al. (Hinge region of Arabidopsis phyA plays an important role in regulating phyA function, 2018, PNAS, 115: E11864–E11873), Sheehan et al. (Structure and Expression of Maize Phytochrome Family Homeologs, 2004, Genetics, 167: 1395–1405) and Schmidt et al. (The evolving landscape around genome editing in agriculture, 2020, EMBO Reports, 21:e50680). This is a new rejection necessitated by claim amendments.
Claim 1 is drawn to a corn plant or part thereof comprising at least one mutation in the hinge region but not in the S600 amino acid residue (with reference to SEQ ID NO: 71 or SEQ ID NO: 74) of the endogenous PHYA gene wherein the encoded PHYA polypeptide comprises the amino acid sequence of GTLNDASKPAQASG (SEQ ID NO: 80), and wherein the corn plant exhibits a reduced Shade Avoidance Response as compared to a control corn plant.
Claim 23 depends from claim 1 and is drawn to the at least one mutation results in a mutated PHYA polypeptide having at least 90% sequence identity to any one of SEQ ID NOs: 93-95.
Christensen et al. teaches an endogenous corn PHYA2 gene (GenBank Accession No. AY260865) encoding a PHYA2 polypeptide containing a hinge region consisting of SEQ ID NOs: 79-80, as highlighted in lighter grey (top two rows) in the sequence alignment, as shown below.
ZmPHYA1 MSSLRPAQSSSSSSRTRQSSQARILAQTTLDAELNAEYEESGDSFDYSKLVEAQRSTPPE
ZmPHYA2 MSSSRPAHSSSSSSRTRQSSRARILAQTTLDAELNAEYEESGDSFDYSKLVEAQRSTPPE
AsPHYA --MSSSRPASSSSSRNRQSSQARVLAQTTLDAELNAEYEESGDSFDYSKLVEAQRDGPPV
. :******.****:**:*******************************. **
ZmPHYA1 QQGRSGKVIAYLQHIQRGKLIQPFGCLLALDEKSFRVIAFSENAPEMLTTVSHAVPNVDD
ZmPHYA2 QQGRSGKVIAYLQHIQRGKLIQPFGCLLALDEKSFRVIAFSENAPEMLTTVSHAVPNVDD
AsPHYA QQGRSEKVIAYLQHIQKGKLIQTFGCLLALDEKSFNVIAFSENAPEMLTTVSHAVPSVDD
***** **********:*****.************.********************.***
ZmPHYA1 PPKLGIGTNVRSLFTDPGATALQKALGFADVSLLNPILVQCKTSGKPFYAIVHRATGCLV
ZmPHYA2 PPKLGIGTNVRSLFTDPGATALQKALGFADVSLLNPILVQCKTSGKPFYAIVHRATGCLV
AsPHYA PPRLGIGTNVRSLFSDQGATALHKALGFADVSLLNPILVQCKTSGKPFYAIVHRATGCLV
**:***********:* *****:*************************************
ZmPHYA1 VDFEPVKPTEFPATAAGALQSYKLAAKAISKIQSLPGGSMQALCNTVVKEVFDLTGYDRV
ZmPHYA2 VDFEPVKPTEFPATAAGALQSYKLAAKAISKIQSLPGGSMEALCNTVVKEVFDLTGYDRV
AsPHYA VDFEPVKPTEFPATAAGALQSYKLAAKAISKIQSLPGGSMEVLCNTVVKEVFDLTGYDRV
****************************************:.******************
ZmPHYA1 MAYKFHEDEHGEVFAEITKPGIEPYLGLHYPATDIPQAARFLFMKNKVRMICDCRARSVK
ZmPHYA2 MAYKFHEDEHGEVFAEITKPGIEPYIGLHYPATDIPQAARFLFMKNKVRMICDCRARSVK
AsPHYA MAYKFHEDDHGEVFSEITKPGLEPYLGLHYPATDIPQAARLLFMKNKVRMICDCRARSIK
********:*****:******:***:**************:*****************:*
ZmPHYA1 IIEDEALSIDISLCGSTLRAPHSCHLQYMENMNSIASLVMAVVVNENEDDDEPESEQPPQ
ZmPHYA2 IIEDEALSIDISLCGSTLRAPHSCHLKYMENMNSIASLVMAVVVNENEEDDEPEPEQPPQ
AsPHYA VIEAEALPFDISLCGSALRAPHSCHLQYMENMNSIASLVMAVVVNENEEDDEAESEQPAQ
:** ***.:*******:*********:*********************:***.*.***.*
ZmPHYA1 QQKRKKLWGLIVCHHESPRYVPFPLRYACEFLAQVFAVHVNKEFELEKQIREKSILRMQT
ZmPHYA2 QQKKKRLWGLIVCHHESPRYVPFPLRYACEFLAQVFAVHVNKEFELEKQIREKNILRMQT
AsPHYA QQKKKKLWGLLVCHHESPRYVPFPLRYACEFLAQVFAVHVNREFELEKQLREKNILKMQT
***:*:****:******************************:*******:***.**:***
ZmPHYA1 MLSDMLFKESSPLSIVSGSPNIMDLVKCDGAALLYGDKVWRLQTAPTESQIRDIAFWLSE
ZmPHYA2 MLSDMLFKESSPLSIVSGSPNIMDLVKCDGAALLYGDKVWRLQTAPTESQIRDIAFWLSE
AsPHYA MLSDMLFREASPLTIVSGTPNIMDLVKCDGAALLYGGKVWRLRNAPTESQIHDIAFWLSD
*******:*:***:****:*****************.*****:.*******:*******:
ZmPHYA1 VHGDSTGLSTDSLQDAGYPGAASLGDMICGMAVAKITSKDILFWFRSHTAAEIKWGGAKH
ZmPHYA2 VHGDSTGLSTDSLQDAGYPGAASLGDMICGMAVAKITSKDILFWFRSHTAAEIKWGGAKH
AsPHYA VHRDSTGLSTDSLHDAGYPGAAALGDMICGMAVAKINSKDILFWFRSHTAAEIRWGGAKN
** **********:********:*************.****************:*****:
[AltContent: rect]
ZmPHYA1 DPSDEDDSRRMHPRLSFKAFLEVVKMKSLPWSDYEMDAIHSLQLILRGTLNDALKPAQSS
ZmPHYA2 DPSDKDDNRRMHPRLSFKAFLEVVKTKSLPWSDYEMDAIHSLQLILRGTLNDASKPAQAS
AsPHYA DPSDMDDSRRMHPRLSFKAFLEVVKMKSLPWSDYEMDAIHSLQLILRGTLNDASKPKREA
**** **.***************** *************************** ** : :
ZmPHYA1 GLDNQIGDLKLDGLAELQAVTSEMVRLMETATVPILAVDGNGLVNGWNQKVADLSGLRVD
[AltContent: rect]ZmPHYA2 GLDNQIGDLKLDGLAELQAVTSEMVRLMETATVPILAVDGNGLVNGWNQKVAELSGLRVD
AsPHYA SLDNQIGDLKLDGLAELQAVTSEMVRLMETATVPILAVDGNGLVNGWNQKAAELTGLRVD
.*************************************************.*:*:*****
ZmPHYA1 EAIGRHILTLVEDSSVPIVQRMLYLALQGREEKEVRFELKTHGSKRDDGPVILVVNACAS
ZmPHYA2 EAIGRHILTLVEDSSVSLVQRMLYLALQGREEKEVRFELKTHGSKRDDGPVILVVNACAS
AsPHYA DAIGRHILTLVEDSSVPVVQRMLYLALQGKEEKEVRFEVKTHGPKRDDGPVILVVNACAS
:***************.:***********:********:****.****************
ZmPHYA1 RDMHDHVVGVCFVAQDMTVHKLVMDKFTRVEGDYRAIIHNPNPLIPPIFGADQFGWCSEW
ZmPHYA2 RDLHDHVVGVCFVAQDMTVHKLVMDKFTRVEGDYKAIIHNPNPLIPPIFGADQFGWCSEW
AsPHYA RDLHDHVVGVCFVAQDMTVHKLVMDKFTRVEGDYKAIIHNPNPLIPPIFGADEFGWCSEW
**:*******************************:*****************:*******
ZmPHYA1 NAAMTKLTGWHRDEVIDRMLLGEVFDSSNASCLLKSKDAFVRLCIIINSALAGEEAEKAP
ZmPHYA2 NAAMTKLTGWHRDEVVDKMLLGEVFNSSNASCLLKSKDAFVRLCIVINSALAGEEAEKAS
AsPHYA NAAMTKLTGWNRDEVLDKMLLGEVFDSSNASCPLKNRDAFVSLCVLINSALAGEETEKAP
**********:****:*:*******:****** **.:**** **::*********:***.
ZmPHYA1 IGFFDRDGKYIECLLSVNRKVNADGVVTGVFCFIHVPSDDLQHALHVQQASEQTALRRLK
ZmPHYA2 FGFFDRNEKYVECLLSVNRKVNADGVVTGVFCFIHVPSDDLQHALHVQQASEQTAQRKLK
AsPHYA FGFFDRSGKYIECLLSANRKENEGGLITGVFCFIHVASHELQHALQVQQASEQTSLKRLK
:*****. **:*****.*** * .*::*********.*.:*****:********: ::**
ZmPHYA1 AFSYMRHAIDKPLSGMLYSRETLKGTDLDEEQMRQVRVADNCHRQLNKILADLDQDNITD
ZmPHYA2 AFSYMRHAINKPLSGMLYSRETLKSTGLNEEQMRQVRVGDNCHRQLNKILADLDQDNITD
AsPHYA AFSYMRHAINNPLSGMLYSRKALKNTDLNEEQMKQIHVGDNCHHQINKILADLDQDSITE
*********::*********::**.*.*:****:*::*.****:*:**********.**:
ZmPHYA1 KSSCLDLDMAEFVLQDVVVSAVSQVLIGCQGKGIRVACNLPERSMKQKVYGDGIRLQQIL
ZmPHYA2 KSSCLDLDMAEFVLQDVVVSAVSQVLIGCQAKGIRVACNLPERSMKQKVYGDGIRLQQIV
AsPHYA KSSCLDLEMAEFLLQDVVVAAVSQVLITCQGKGIRISCNLPERFMKQSVYGDGVRLQQIL
*******:****:******:******* **.****::****** ***.*****:*****:
ZmPHYA1 SDFLFVSVKFSPAGGSVDISSKLTKNSIGENLHLIDFELRIKHQGAGVPAEILSQMYGED
ZmPHYA2 SDFLFVSVKFSPAGGSVDISSKLTKNSIGENLHLIDFELRIKHRGAGVPAEILSQMYEED
AsPHYA SDFLFISVKFSPVGGSVEISSKLTKNSIGENLHLIDLELRIKHQGLGVPAELMAQMFEED
*****:******.****:******************:******:* *****:::**: **
ZmPHYA1 NREQSEEGLSLLVSRNLLRLMNGDIRHLREAGMSTFILTAELAAAPSAAGH
ZmPHYA2 NKEQSEEGFSLAVSRNLLRLMNGDIRHLREAGMSTFILTAELAAAPSAVGR
AsPHYA NKEQSEEGLSLLVSRNLLRLMNGDVRHLREAGVSTFIITAELASAPTAMGQ
*:******:** ************:*******:****:*****:**:* *:
The corn PHYA2 polypeptide also has more than 90% (99.0%) sequence identity to instant SEQ ID NO: 95, as recited in claim 23. Christensen et al. also teach that phytochrome is synthesized de-novo in the Pr form and upon red light mediated conversion to the Pfr form, induces a wide variety of photomorphogenic responses (page 382, left column, para 1, line 3-6), which reads on to “capable of regulating response to illumination”, as recited in claim 2.
However, Christensen et al. does not describe at least one mutation in the hinge region in the endogenous PHYA2 gene. It also does not teach any shade avoidance response.
Kohichi et al. describe the hinge region starting from amino acid position 541 to 620 (as highlighted in darker grey in the sequence alignment above) connecting photosensory domain with the regulatory domain in the oat (A. sativa) Phychrome A protein (col. 4, line 61-64; Fig. 1) comprising a serine at position 598. Kohichi et al. also describes a modified PHYA polypeptide by substituting serine-598 (with alanine) or its functional equivalent(s) in oat phytochrome A or in other phytochrome As from dicotyledonous (e.g., Arabidopsis) or monocotyledonous plants (column 6, line 15-18). The modified oat PHYA (SEQ ID NO: 2) polypeptide possesses similar or even greater physiological activity compared to that of wild type PHYA (SEQ ID NO: 4) polypeptide in reducing or suppressing shade avoidance response (column 6, line 19-22). The modified oat phytochrome A gene with an alanine codon replacing the endogenous serine codon giving rise to S598A mutation, which, when expressed, significantly reduce shade avoidance (abstract).
Kohichi et al. describe phosphorylation of S598 is important for the phytochrome function (column 6, line 53-54) and the plant develops a shade avoidance trait when the S598 is substituted with alanine (A) by site-directed mutagenesis (column 4, line 64-67; column 5, line 1-2).
Sequence alignment of the endogenous corn ZmPHYA1 (GenBank Accession No. AY234826, published in 2004 by Sheehan et al.), ZmPHYA2 (GenBank Accession No. AY260865,as taught by Christensen et al.) and the oat AsPHYA protein (SEQ ID NO: 4, as described by Kohichi et al.) containing an endogenous S598 amino acid (serine residue in the box at the bottom row with darker highlight) in SEQ ID NO: 4 as taught by Kohichi et al., indicates that the crucial S598 in the hinge region is interpreted as a functional equivalent of the serine reside S600 (as recited in claims 1 and 11) in the hinge region of the corn PHYA2 proteins (grey highlighted serine residue in the upper box), as shown above.
Zhou et al. describes the role of hinge region in PHYA polypeptide (abstract). Zhou et al. describes two (S590 and T593) sites in the hinge region of Arabidopsis phyA (besides S602, which is equivalent to S600 in ZmPHYA) are essential in regulating phyA function including phosphorylation of PHYA protein (abstract, line 8-14), which plays a crucial role in far-red light response, which is known to influence shade avoidance trait in a plant (Kohichi et al.; column 2, line 48-63).
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Zhou et al. also compares the hinge region sequences of monocot and dicot PHYA proteins (Fig. S1), as shown above. Zhou et al. describes mutating the S590, T593, and/or S602 of Arabidopsis PHYA protein to aspartic acid (D), individually or together (p. E11865, right column, para 3, line 1-2).
Before the effective filing date of the invention, it would have been obvious to an ordinarily skilled artisan to mutate one or both the endogenous amino acid residue(s) equivalent to T593 (i.e., K595), as in the Arabidopsis PHYA protein, in the hinge region of endogenous corn PHYA protein, as shown within the black box above. It would also have been obvious to an ordinarily skilled artisan to edit the endogenous PHYA2 gene using the well-known standard technique of CRISPR-Cas to get in-frame deletion (as recited in claims 11-12, 14 and 16) mutation(s) that disrupt the structure of the PHYA protein including mutating/deleting the S594 and/or K595, in reference to instant SEQ ID NO: 74, in the hinge region of the corn PHYA protein(s) with a realistic goal to achieve the shade avoidance trait.
Before the effective filing date, one with ordinary skill in the art would have been motivated to mutate the endogenous amino acid residue(s) S594, K595 in the hinge region of corn PHYA proteins (PHYA1 and/or PHYA2) encoded by PHYA genes using standard methods like targeted gene editing (e.g., CRISPR-Cas) with a realistic goal to develop the shade avoidance trait, as evident in Zoysiagrass as described by Kohichi et al.(column 1, line 35-42), in the genome edited corn plant comprising mutation(s) in the hinge region of the PHYA protein. One with ordinary skill in the art also would know that many countries starting with Australia and now comprising USA and Canada besides others, do not impose regulatory constraints, which are valid for transgenic crops or GMOs, on genome edited crops, as described by Schmidt et al. (Fig. 1). The artisan would have been motivated to edit the endogenous PHYA gene in corn as compared to expressing a transgene comprising the mutated PHYA gene in corn.
Regarding claim 2, phytochrome is a well-known and the best characterized photoreceptor controlling light response and photomorphogenesis in plants (Christensen et al., page 381, right column, para 1), capable of regulating response to illumination in plants including a corn plant.
Regarding claim 13, the PHYA2 polypeptide described by Kohichi et al. comprises four amino acid substitutions (which implies substituting an A, a T, a G or a C) in the hinge region (e.g., S600A substitution) of instant SEQ ID NO: 74, as discussed above.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAY CHATTERJEE whose telephone number is (703)756-1329. The examiner can normally be reached (Mon - Fri) 8.30 am to 5.30 pm..
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Jay Chatterjee
Patent Examiner
Art Unit 1662
/Jay Chatterjee/Examiner, Art Unit 1662
/BRATISLAV STANKOVIC/ Supervisory Patent Examiner, Art Units 1616 & 1662
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