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 .
As notified earlier in the Interview Summary (dated 11/13/2025), following is the second Non-Final Office action.
The delay in prosecution is regretted.
Election/Restrictions
Applicant’s election of species without traverse in the reply filed on 6/27/2025 is acknowledged.
Applicant elects the following species without traverse,
Solanum lycopersicum SlARF8B
SEQ ID NO: 83
Solanum lycopersicum SlARF8B comprising a deletion in amino acids 715-803
of SEQ ID NO: 83
Solanum lycopersicum SlARF8B and wherein amino acids 715-803 of SEQ ID
NO: 83 or a portion thereof are deleted
A truncated SlARF8B comprising amino acids 1-714 of SEQ ID NO: 83
A Solanaceae plant
However, Arabidopsis thaliana AtARF8 is rejoined.
The election is made FINAL.
Claim Status
Claims 1-37 are pending and being examined.
Claim Objections
Applicant is advised that should claim 3 be found allowable, claim 10 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 7-9, 11-13, 15-17, 20-23, 27, 30 and 34 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.
Regarding claims 7-8, claim 7 recites the limitation "the S1ARF8A" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 7 depends from claim 1 and there is no recitation of any “S1ARF8A” in claim 1.
Regarding claim 9, it is not clear if the “(IAA9)” recited within the parenthesis is a claim limitation or an example of “Solanum lycopersicum IAA”. It is unclear what the term “IAA9” refers to in the context of the claim.
Regarding claims 11-13 and 20-23, it is not clear, in claim 11 (and all claims directly or indirectly dependent from claim 11), if the “modified S1ARF8A comprises a deletion in amino acids 716-804 of SEQ ID NO: 1” encompasses the full-length sequence of amino acids 716-804 of SEQ ID NO: 1 or any portion of the amino acids 716-804 of SEQ ID NO: 1.
Regarding claims 13 and 20-23, it is not clear if the “the modified S1ARF8A …. comprising amino acids 1-716 of SEQ ID NO: 1” encompasses the full-length sequence of amino acids 1-716 of SEQ ID NO: 1 or any portion thereof.
Regarding claims 15-17, it is not clear, in claim 15, if the “modified S1ARF8A ortholog comprises Solanum lycopersicum S1ARF8B comprising a deletion in amino acids 715-803 of SEQ ID NO: 83” encompasses deletion of the full-length sequence of amino acids 715-803 of SEQ ID NO: 83 or any portion of amino acids 715-803 of SEQ ID NO: 83.
Regarding claim 17, it is not clear if the “truncated SlARF8B comprising amino acids 1-714 of SEQ ID NO: 83” encompasses the full-length sequence of amino acids 1-714 of SEQ ID NO: 83 or any portion of amino acids 1-714 of SEQ ID NO: 83.
Claim 23 recites the limitation "the Solanum plant" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claims 23 depends from claim 21, which in turn depends from claim 20, which in turn depends from claim 13. There is no recitation of any Solanum plant in either claim 20 or claim 13 either.
Claim 27 recites the limitation "the temperature stress" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claims 27 depends from claim 1. There is no recitation of any “temperature stress” in claim 1 either.
Claim 30 recites the limitation "the amount" in line 1. There is insufficient antecedent basis for this limitation in the claim. It is also not clear what the Applicant mean by the terms “amount” and “activity”. It is not clear if the “amount” refers to the amount (relative number) of ARF8 transcripts, or protein molecules, or copy number of ARF8 allele(s). It is also not clear if the term “activity” refers to biochemical activities including transcription activity and/or translational activity of the ARF8 gene, or biological activity in terms of its phenotype.
Regarding claim 34, it is not clear what the applicant exactly means by “contacting” in line 2. Simply “contacting” a plant cell with an expression construct would not modify the plant cell. Therefore the claim never accomplishes what is recited in the preamble. It is suggested to replace the term “contacting” with “transforming” or similar phrase.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-8, 10-13, 15-16, 19-23, 25-26 and 28-29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Goetz et al. (Expression of Aberrant Forms of AUXIN RESPONSE FACTOR8 Stimulates Parthenocarpy in Arabidopsis and Tomato, 2007, Plant Physiology, 145:351–366), in evidence of Pandolfini, T (Seedless Fruit Production by Hormonal Regulation of Fruit Set, 2009, Nutrients, 1:168-177).
Claim 1 is drawn to a genetically modified flowering plant that expresses a modified Auxin Response Factor 8A (ARF8A) or an ortholog thereof, comprising a mutation in a Phox and Beml (PB1) domain, and wherein the flowering produces ovary-derived, seedless fruit.
Goetz et al. describes genetically modified flowering plants that express an allele of Arabidopsis ARF8 (atarf8-4) gene and a tomato SlARF8 gene (abstract). The Arabidopsis and tomato ARF8 proteins are orthologs (page 356, right column, para 1). Tomato ARF8 protein (GenBank Accession No. EF667342) is also an ortholog of tomato ARF8A polypeptide consisting of SEQ ID NO: 1 and share high sequence identity to instant SEQ ID NO: 1, as shown below.
Title: US-18-629-315-1
Perfect score: 4457
Sequence: 1 MKLSTSGMGQQAHEGENKCL..........NSADGRDFMSGLPSIGSLDY 844
Searched: 1 seqs, 843 residues
Database : AASEQ2_07312025_163623.pep:*
RESULT 1
AASEQ2_07312025_163623
Query Match 87.3%; Score 3891; DB 1; Length 843; Best Local Similarity 88.2%;
Matches 747; Conservative 39; Mismatches 53; Indels 8; Gaps 6;
Qy 1 MKLSTSGMGQQAHEGENKCLNSELWHACAGPLVCLPTVGSRVVYFPQGHSEQVAATTNKE 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MKLSTSGMGQQAHEGENKCLNSELWHACAGPLVCLPTVGSRVVYFPQGHSEQVAATTNKE 60
Qy 61 VDIHIPNYPNLPPQLICQLHNVTMHADVETDEVYAQMTLQPLTLQEQKDTYLPVELGIPS 120
:|||||||||||||||| ||||||||||||||||||||||||||||||||||||||||||
Db 61 LDIHIPNYPNLPPQLICPLHNVTMHADVETDEVYAQMTLQPLTLQEQKDTYLPVELGIPS 120
Qy 121 RQPTNYFCKTLTASDTSTHGGFSVPRRAAEKVFPPLDFSQTPPCQELIARDLHDIEWKFR 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 RQPTNYFCKTLTASDTSTHGGFSVPRRAAEKVFPPLDFSQTPPCQELIARDLHDIEWKFR 180
Qy 181 HIFRGQPKRHLLTTGWSVFVSAKRLVAGDSVLFIWNEKNQLFLGIRRATRPQTVMPSSVL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 HIFRGQPKRHLLTTGWSVFVSAKRLVAGDSVLFIWNEKNQLFLGIRRATRPQTVMPSSVL 240
Qy 241 SSDSMHIGLLAAAAHAASTNSCFIVFFNPRASPSEFVIPLSKYIKAVYHTRVSVGMRFRM 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 SSDSMHIGLLAAAAHAASTNSCFIVFFNPRASPSEFVIPLSKYIKAVYHTRVSVGMRFRM 300
Qy 301 LFETEESSVRRYMGTITGIGDLDPVRWANSHWRSVKVGWDESTAGERQPRVSLWEIEPLT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 LFETEESSVRRYMGTITGIGDLDPVRWANSHWRSVKVGWDESTAGERQPRVSLWEIEPLT 360
Qy 361 TFPMYPSLFPLRLKRPWYPGTSSFQENNSEAINGMTWLRGESSEQGPHLLNLQSFGGMFP 420
||||||||||||||||:| ||||:|::|:|||| |:|||| : | | | :||||| || |
Db 361 TFPMYPSLFPLRLKRPFYQGTSSYQDSNNEAINRMSWLRGNAGELGHHSMNLQSF-GMLP 419
Qy 421 WMQQRVDPTMLRNDLNQQYQAMLASGLQNFGSGDLMKQQLMQFPQPVQYVQHAGSVNPQL 480
||||||| |:| ||:|| ||||||:|||:||||||:||||||| |||||:||| : | |
Db 420 WMQQRVDSTILPNDINQHYQAMLATGLQSFGSGDLLKQQLMQFQQPVQYLQHASTENSIL 479
Qy 481 -QQQQQQQETMQQTIHHHMLPAQTQ---DNLQRQQQQHVSNQTEEQSHQHSYQDAYQIPN 536
|||||||: ||| :| |||||||| :||||| | :||:|||:|||:||:|:|:|:
Db 480 HQQQQQQQQIMQQAVHQHMLPAQTQMLSENLQRQSQHQSNNQSEEQAHQHTYQEAFQLPH 539
Qy 537 SQLQQKQPSNVPSPSFSKPDIADPSSKFSASIAPSGMPTALGSLCSEGTTNFLNFNIIGQ 596
||||:||||| || | | | || :||||||:||||: ||||||||: | || | ||
Db 540 DQLQQRQPSNVTSP-FLKADFADLTSKFSASVAPSGVQNMLGSLCSEGSNNSLNINRTGQ 598
Qy 597 QPVIMEQQQQQKSWMAKFANSQLNMGSSSPSLSGYGKETSNSQETCSLDAQNQSLFGANV 656
||:|| || |||:|| |||| |:| || |||:| | : ||||:||||||||||
Db 599 S-VIIEQSPQQ-SWMSKFTESQLNTCSNSSSLPTYGKDTFNPRGNCSLDSQNQSLFGANV 656
Qy 657 DSSGLLLPTTVSNVATTSIDADISSMPLGTSGFPNPLYSYVQDSTDLLHNVGQADAQTVP 716
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 657 DSSGLLLPTTVSNVATTSIDADISSMPLGTSGFPNPLYSYVQDSTDLLHNVGQADAQTVP 716
[AltContent: rect][AltContent: rect]
Qy 717 RTFVKVYKSASLGRSLDITRFNSYHELRQELGQMFGIEGFLENPQRSGWQLVFVDRENDV 776
||||||||||||||||||||||||||||||||||||||| ||:|||||||||||||||||
Db 717 RTFVKVYKSASLGRSLDITRFNSYHELRQELGQMFGIEGLLEDPQRSGWQLVFVDRENDV 776
Qy 777 LLLGDDPWEEFVNNVWYIKILSPEDVQKLGKEEVGSLNRGPPERMSSNNSADGRDFMSGL 836
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 777 LLLGDDPWEEFVNNVWYIKILSPEDVQKLGKEEVGSLNRGPPERMSSNNSADGRDFMSGL 836
Qy 837 PSIGSLD 843
|||||||
Db 837 PSIGSLD 843
It also teaches that mutations in the AUXIN RESPONSE FACTOR8 (ARF8) uncouple fruit initiation from fertilization resulting in the formation of seedless, parthenocarpic fruit (abstract).
The Phox and Bem1 (PB1) domain of SlARF8 (GenBank Accession No. EF667342) is from amino acid residues 717-801 (highlighted in darker grey in the sequence alignment above, as predicted by Uniprot), which correlates with the PB1 domain comprising of amino acid at position 712 to 811 (page 3, para 0014; Fig. 1a) of SlARF8A (SEQ ID NO: 1). There are several mutations in the PB1 domain of SlARF8 (GenBank Accession No. EF667342) aligning with the PB1 domain spanning from amino acid at 712 to amino acid at 811 (highlighted in lighter grey, above) in SEQ ID NO: 1 (Instant Fig. 1A).
It is well acknowledged in the art that the onset of fruit development starts in ovary after fertilization of the ovules (evidence from Pandolfini, T; abstract). All fruits, irrespective of fertilization of the ovule, are derived from ovaries and fruit growth can be uncoupled from fertilization and seed development (Pandolfini, T, page 168, para 1, line 5-6) to develop seedless fruits.
Regarding claim 2, there are two mutations (shown within the boxes in the sequence alignment above) resulting in amino acid substitution in the Phox and Bem1 (PB1) domain of SlARF8 (GenBank Accession No. EF667342), as described by Goetz et al., aligning with the PB1 domain of SlARF8A consisting of SEQ ID NO: 1 (Instant Fig. 1A).
Regarding claim 3, Goetz et al. describes two mutations (shown within the red boxes in the sequence alignment above) in the PB1 domain of SlARF8, as described above.
Regarding claim 4, Goetz teaches that both Arabidopsis and tomato possess ARF8 and (Aux/IAA protein) IAA9-like orthologs and they interact. Together with potentially other as yet unknown proteins, these proteins form a complex that prevents fruit set prior to fertilization (page 352, left column, para 1). Mutations in ARF8 prevent the production of a functional protein so that the complex cannot form (page 352, right column, para 1). It also describes that antisense repression of IAA9 in tomato and recessive mutations in Arabidopsis ARF8 uncoupled fruit initiation from pollination and fertilization and gave rise to parthenocarpic fruit (page 351, right column, last para, last 5 lines). Aux/IAA proteins (including IAA9) bind to ARF proteins to activate or inhibit the transcription of auxin responsive genes (page 351, right column, last para, last line and page 352, left column, first para, first 2 lines). It all implies that the interaction between the modified ARF8A ortholog comprising 5-bp deletion in the SlARF8 (page 358, left column, para 2) and the ataraf8-4 with one or more auxin responsive protein(s) in the transgenic plant is reduced, if not abolished, due to the mutation in the ARF8 ortholog giving rise to parthenocarpic fruits.
Regarding claim 5, Goetz teaches Aux/IAA protein IAA9 (page 351, right column, para 2, line 7-8).
Regarding claim 6, Goetz et al. describes genetically modified flowering plants wherein the modified ARF8 is an ortholog of Solanum lycopersicum ARF8A (SIARF8A) (page 359, left column, para 3, line 1-3). Goetz et al. also describes Arabidopsis AtARF8 (abstract) and two mutant alleles of AtARF8 (atarf8-1 and atarf8-4) (page 352, left column, para 2, line 11-14), which are orthologs of SlARF8A, as discussed above.
Regarding claim 7, Goetz et al. teaches several orthologs of Solanum lycopersicum ARF8A (SIARF8A) including atarf8-1, and atarf8-4, as described above, besides SlARF8 (abstract) which is also an ortholog of SlARF8A.
Regarding claim 8, Goetz et al. teaches a polypeptide (SIARF8) (GenBank Accession No. EF667342; Protein id: ABS83388.1) having more than 90% sequence identity to SEQ ID NO: 83, as shown below.
Title: US-18-629-315-83
Perfect score: 4439
Sequence: 1 MKLSTSGMGQQAHEGGEKKC..........TNADDRDLISGMPSLGSLEY 842
Searched: 1 seqs, 844 residues
Database : AASEQ2_08042025_101038.pep:*
RESULT 1
AASEQ2_08042025_101038
Query Match 92.6%; Score 4109; DB 1; Length 844; Best Local Similarity 92.7%;
Matches 783; Conservative 20; Mismatches 38; Indels 4; Gaps 3;
Qy 1 MKLSTSGMGQQAHEGGEKKCLNSELWHACAGPLVCLPTVGSRVVYFPQGHSEQVAATTNK 60
|||||||||||||| || ||||||||||||||||||||||||||||||||||||||||||
Db 1 MKLSTSGMGQQAHE-GENKCLNSELWHACAGPLVCLPTVGSRVVYFPQGHSEQVAATTNK 59
Qy 61 EVDAHIPNYPNLSPQLICQLHNVTMHADVETDEVYAQMTLQPLTPEEQKDTYLPVEFGIP 120
|:| |||||||| ||||| ||||||||||||||||||||||||| :|||||||||| |||
Db 60 ELDIHIPNYPNLPPQLICPLHNVTMHADVETDEVYAQMTLQPLTLQEQKDTYLPVELGIP 119
Qy 121 SKQPTNYFCKTLTASDTSTHGGFSVPRRAAEKVFPPLDFSQTPPAQELIARDLHDVEWKF 180
|:|||||||||||||||||||||||||||||||||||||||||| ||||||||||:||||
Db 120 SRQPTNYFCKTLTASDTSTHGGFSVPRRAAEKVFPPLDFSQTPPCQELIARDLHDIEWKF 179
Qy 181 RHIFRGQPKRHLLTTGWSVFVSAKRLVAGDSVLFIWNEKNQLLLGIRRAVRPQTVMPSSV 240
|||||||||||||||||||||||||||||||||||||||||| |||||| ||||||||||
Db 180 RHIFRGQPKRHLLTTGWSVFVSAKRLVAGDSVLFIWNEKNQLFLGIRRATRPQTVMPSSV 239
Qy 241 LSSDSMHIGLLAAAAHAAATNSCFNVFFNPRASPSEFVIPLSKYIKAVYHTRVSVGMRFR 300
||||||||||||||||||:||||| |||||||||||||||||||||||||||||||||||
Db 240 LSSDSMHIGLLAAAAHAASTNSCFIVFFNPRASPSEFVIPLSKYIKAVYHTRVSVGMRFR 299
Qy 301 MLFETEESSVRRYMGTITGIGDLDPVRWANSHWRSVKVGWDESTAGERQPRVSLWEIEPL 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 300 MLFETEESSVRRYMGTITGIGDLDPVRWANSHWRSVKVGWDESTAGERQPRVSLWEIEPL 359
Qy 361 TTFPMYPSLFPLRLKRPFYQGTSSYQDSNNEAINRMSWLRGNAGELGHHSMNLQSFGMLP 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 360 TTFPMYPSLFPLRLKRPFYQGTSSYQDSNNEAINRMSWLRGNAGELGHHSMNLQSFGMLP 419
Qy 421 WMQQRVDSTILPNDINQHYQAMLATGLQSFGSGDLLKQQLMQFQQPVQYLQHASTENSIL 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 420 WMQQRVDSTILPNDINQHYQAMLATGLQSFGSGDLLKQQLMQFQQPVQYLQHASTENSIL 479
Qy 481 HQQQQQQQQIMQQAVHQHMLPAQTQMLSENLQRQSQHQSNNQSEEQAHQHTYQEAFQLPH 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 480 HQQQQQQQQIMQQAVHQHMLPAQTQMLSENLQRQSQHQSNNQSEEQAHQHTYQEAFQLPH 539
Qy 541 DQLQQRQPSNVTSPFLKADFADLTSKFSASVAPSGVQNMLGSLCSEGSNNSLNINRTGQS 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 540 DQLQQRQPSNVTSPFLKADFADLTSKFSASVAPSGVQNMLGSLCSEGSNNSLNINRTGQS 599
Qy 601 VIIEQSPQQSWMSKFTESQLNTCSNSSSLPTYGKDTSNPRGNCSLDSQNQALFGANIDSS 660
|||||||||||||||||||||||||||||||||||| |||||||||||||:|||||:|||
Db 600 VIIEQSPQQSWMSKFTESQLNTCSNSSSLPTYGKDTFNPRGNCSLDSQNQSLFGANVDSS 659
Qy 661 GHLLPTTVSNVTTTC--ADMSLMPLGASGYQNSLYGYVQDSSELLHNAGQIDPPNATHTF 718
| ||||||||| || ||:| |||| ||: | || |||||::|||| || | ||
Db 660 GLLLPTTVSNVATTSIDADISSMPLGTSGFPNPLYSYVQDSTDLLHNVGQADAQTVPRTF 719
Qy 719 VKVYKSGCVGRSLDITQFHSYHELRRELGQMFGIEGFLEDPQRSGWQLVFVDRENDILLL 778
|||||| :|||||||:|:||||||:|||||||||| |||||||||||||||||||:|||
Db 720 VKVYKSASLGRSLDITRFNSYHELRQELGQMFGIEGLLEDPQRSGWQLVFVDRENDVLLL 779
Qy 779 GDDPWEAFVNNVWYIKILSPEDVQKLGKEEAESLNRGAVERMSSTN-ADDRDLISGMPSL 837
|||||| ||||||||||||||||||||||| ||||| ||||| | || || :||:||:
Db 780 GDDPWEEFVNNVWYIKILSPEDVQKLGKEEVGSLNRGPPERMSSNNSADGRDFMSGLPSI 839
Qy 838 GSLEY 842
|||:|
Db 840 GSLDY 844
Regarding claims 10-12, Goetz et al. describes identifying a SlARF8 cDNA sequence comprising a 5-bp deletion in the DNA binding domain of the encoded polypeptide. The deletion introduced an early stop codon immediately after the deletion within in a truncated AFR8 protein containing N-terminal 185 amino acids (page 358, left column, para 2, line 1-9; Fig. 6A), wherein all of its PB1 domain consisting of amino acid residues 712-811 (Spec, page 4, para 0014; Fig. 1a), as discussed above, is deleted.
Regarding claim 13, the 5-bp deletion in the DNA binding domain of the encoded polypeptide introduces a stop codon immediately after the deletion resulting in a polypeptide consisting of amino acids 1-185, as discussed above. The polypeptide is interpretated as a truncated SlARF8A comprising part of the amino acids 1-716 of SEQ ID NO: 1.
Regarding claims 15-16, claims 15-16 are drawn to a genetically modified flowering plant of claim 6, wherein the modified S1ARF8A ortholog comprises Solanum lycopersicum S1ARF8B comprising a deletion of full length or a portion of amino acids 715-803 of SEQ ID NO: 83. As SlARF8A and SlARF8B are orthologs, the Examiner interprets claims 15-16 would include a S1ARF8A ortholog comprising a deletion that includes deletion of all of amino acids 715-803 of SEQ ID NO: 83. Thus, the genetically modified flowering plant containing an ortholog of SlAFR8, as described by Goetz et al. and as discussed above, fulfils all the claim limitations of the claims 15-16.
Regarding claim 19, tomato and Arabidopsis plants, as described by Goetz et al., belong to Angiospermae (flowering plant) (Wikipedia).
Regarding claims 20-23, the genetically modified tomato plants (Solanum lycopersicum), as described by Goetz et al., is a Solanaceae plant, as known in the art.
Regarding claim 25, , Goetz et al. teaches that parthenocarpy is a desirable trait in horticultural crops, as it enables fruit set and growth to be independent of pollination, fertilization, and seed development. Thus, it circumvents the environmental constraints
on fruit production and ensure yield stability leading to improving yield (as recited in claim 25) besides other benefits (page 11, right column, last par,a5).
Regarding claim 26, Goetz et al. describes that fruit set in tomato is temperature dependent and commercial fruit quantities because of problems in pollen formation limit fruit set if night temperature is lower than 13°C or when the day temperature is higher than 38°C (page 11, right column, last para, first 6 lines). It implies that any method of fruit setting including parthenocarpy that does not need pollen and, thus, does not encounter the issues fruit setting due to in pollen formation at lower than 13°C or higher than 38°C would exhibit increased yield in terms of fruit yield.
Regarding claims 28-29, Goetz et al. describes a genetically modified flowering plant that express an ortholog of Auxin Responsive Factor 8A (ARF8A). The gene encoding the ortholog of ARF8A comprises a 5-bp deletion mutation that introduces a stop codon immediately after the deletion within the DNA-binding domain around the intro-exon boundary in the genomic sequence (page 358, left column, para 2; Fig. 6a). The deletion mutation deletes the entire PB1 domain, as discussed above.
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 31-34 and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Goetz et al., as applied to claims 1-8, 10-13, 15-16, 19-23, 28-29 above, and further in view of Guilfoyle, TJ (The PB1 Domain in Auxin Response Factor and Aux/IAA Proteins: A Versatile Protein Interaction Module in the Auxin Response, 2015, The Plant Cell, 27: 33–43), and in evidence of Yan et al. (Genome-Wide Identification and Expression Analysis of Auxin Response Factor (ARF) Gene Family in Panax ginseng Indicates Its Possible Roles in Root Development, 2023, Plants, 12:3943) and Sharif et al. (Hormonal interactions underlying parthenocarpic fruit formation in horticultural crops, 2022, Horticulture Research, 2022, 9:uhab024).
Claim 31 is drawn to a genetically modified flowering plant of claim 1, wherein the plant comprises an expression construct, and wherein the expression construct comprises a promoter operably linked to a recombinant nucleic acid sequence encoding ARF8A or an ortholog thereof comprising a mutation in the Phox and Bem l (PB1) domain.
Goetz et al. describes a genetically modified flowering plant wherein the plant comprises an expression construct comprising Atarf8-4 (page 352, left column, para 2, line 11-20) and introducing the Atarf8-4 gene into flowering plants including Arabidopsis (page 352, right column, para 3, line 3-5) and tomato (page 355, left column, last para, last 2 lines). AtARF8 gene, including the atarf8-4 allele, is an ortholog of ARF8A gene, as described above. The expression constructs comprising Atarf8-4 gene are cloned in pBIN19 vector (page 363, right column, last para and page 364, left column, first para). It is well known and widely practiced in the art to clone a nucleic acid sequence encoding the transgene, i.e. atarf8-4 gene in this case, operably linked to a promoter. Goetz et al. also describes that introduction of aberrant molecules, including the atarf8-4 gene, and the 5-bp deletion mutation in the SlARF8 protein deletes the C-terminal protein interaction domain or the PB1 domain in SlARF8 gene (as described above) destabilizes the formation of an inhibitory complex controlling the transition from flower to fruit development, allowing fruit initiation in the absence of fertilization (page 359, right column, last para, line 12-16). It employs dosage effects involving the competitive interference of aberrant proteins, inhibiting the N-terminal DNA-binding domain of ARF8 from binding to the correct promoter sequences in auxin responsive genes, preventing the C-terminal protein interaction domain to bind to Aux/IAA proteins, and/or preventing the dimerization with other proteins that makes up the repressive complex (page 359, right column, last para, last 6 lines and page 360, left column, first 3 lines). The C-terminal protein interaction domain or the C-terminal domain in ARFs is also known as PB1 domain (Yan et al., Genome-Wide Identification and Expression Analysis of Auxin Response Factor (ARF) Gene Family in Panax ginseng Indicates Its Possible Roles in Root Development, 2023, Plants, 12:3943; page 5, para 1, line 3-4).
However, Goetz et al. does not explicitly describe any expression construct comprising a mutation in the Phox and Bem l (PB1) domain.
Guilfoyle, TJ describes modified ARFs where domain III/IV (PB1 domain) is artificially removed from ARFs containing an AD and these modified ARFs constitutively activate auxin response genes in protoplast transfection assays and confer “high auxin” phenotypes when overexpressed in transformed plants ( page 34, right column, last para, last 4 lines and page 35, left column, first para, first line; Fig. 3). “High auxin” phenotype includes induction of parthenocarpic fruits. The treatment of unpollinated ovaries with auxin and its analogs can bypass fertilization and generate seedless (parthenocarpic) fruits in crops plants, such as tomato, cucumber, pear, and watermelon (Sharif et al., Hormonal interactions underlying parthenocarpic fruit formation in horticultural crops, 2022, Horticulture Research, 2022, 9:uhab024; page 4, right column, para 2, first 4 lines)
Before the effective filing date of the invention, it would have been obvious to an ordinarily skilled artisan to mutate the C-terminal domain or the PB1 domain of an ortholog of ARF8A, as described by Goetz et al. and Guilfoyle, TJ, and clone the nucleic acid sequence encoding the modified ARF8A ortholog in an expression construct to transform a flowering plant to produce ovary-derived seedless fruits, as described Goetz et al. (2007).
Before the effective filing date, an ordinarily skilled artisan would have been motivated to mutate the C-terminal domain or the PB1 domain of an ortholog of ARF8A and clone the nucleic acid sequence encoding the modified ARF8A ortholog in an expression construct to transform a flowering plant to produce ovary-derived seedless fruits.
Regarding claim 32, Goetz et al. describes the C-terminal protein interaction domain (CTD) (Fig. 6; page 359, right column, last para, last 6 lines and page 360, left column, first 3 lines), which is also known as PB1 domain, as described above.
Regarding claims 33-34, Goetz et al. describes a method of producing genetically modified flowering plant (page 363 right column, last para and page 364, left column, first para). The method comprises modifying the genome of flowering plant cells is by contacting or transforming the cells with an expression construct comprising a nucleic acid sequence encoding ARF8 ortholog (Atarf8-4) and as described above. Goetz et al. also describes generating flowering plants from the transformed cells in the transgenic seeds of T0 transgenic plants (page 364, left column, para 1-2 and para 9). The transformed plants produce ovary-derived seedless fruits, as described above.
However, Goetz et al. (2007) does not describe introducing a mutation into the nucleic acid sequence of the PB1 domain.
Guilfoyle, TJ describes modified ARFs where domain III/IV (PB1 domain) is artificially removed from ARFs containing an AD and these modified ARFs constitutively activate auxin response genes in protoplast transfection assays conferring “high auxin” phenotypes when overexpressed in transformed plants ( page 34, right column, last para, last 4 lines and page 35, left column, first para, first line; Fig. 3). “High auxin” phenotype includes induction of parthenocarpic fruits, as discussed above.
Before the effective filing date of the invention, it would have been obvious to an ordinarily skilled artisan to mutate the C-terminal domain or the PB1 domain of ARF8A, as described Guilfoyle, TJ, and clone the nucleic acid sequence encoding the modified ARF8A ortholog in an expression construct to transform a flowering plant to produce (parthenocarpic) ovary-derived seedless fruits, as described Goetz et al.
Before the effective filing date, an ordinarily skilled artisan would have been motivated to mutate the C-terminal domain or the PB1 domain of ARF8A and clone the nucleic acid sequence encoding the modified ARF8A ortholog in an expression construct to transform a flowering plant to produce ovary-derived seedless fruits.
Regarding claim 36, Goetz et al. (2007) describes obtaining parthenocarpic fruits from the flowering plants (page 364, left column, para 8, last 2 lines).
Claims 35 and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Goetz et al. in view of Guilfoyle, TJ in evidence of Yan et al. and Sharif et al., as applied to claims 31-34 and 36 above, and further in view of Chen et al. (CRISPR/Cas Genome Editing and Precision Plant Breeding in Agriculture, 2019, Annu. Rev. Plant Biol., 70:667–97).
Claim 35 depends from claim 33, and is drawn to the genome of the one or more flowering plant cells which is modified by using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) gene editing.
Goetz et al. in view of Guilfoyle, TJ describe a method of producing the genetically modified flowering plant wherein the method comprises a) modifying an allele of an arf8a ortholog in the plant cells to introduce a mutation into the nucleic acid sequence of the PB1 domain; and b) generating flowering plants from the transformed plant cells, as described above. However, Goetz et al. in view of Guilfoyle, TJ do not explicitly describe using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) gene editing technique.
Chen et al. describes CRISPR/Cas genome editing technique that allows efficient targeted modification in plants to accelerate crop improvement (abstract). It also describes various mutation breeding techniques including introducing random mutations using chemical or physical irradiation (page 668, last 2 lines). These procedures are restricted by their stochastic nature and generating and screening large numbers of mutants are challenging. Such time-consuming, laborious, untargeted breeding programs cannot keep pace with the demands for increased crop production, even if marker-assisted breeding approaches are adopted to enhance selection efficiency (page 669, first 4 lines). Targeted genome editing using CRISPR/Cas system (page 670, para 2) addresses those issues and provides a simple, efficient, and versatile tool for the study of plant biology and precision plant breeding (page 688, summary, line 1-2).
Before the effective filing date of the invention, it would have been obvious to an ordinarily skilled artisan to mutate an ortholog of ARF8A by introducing a mutation into the PB1 domain, as described by Goetz et al. in view of Guilfoyle, TJ and in evidence of Yan et al. and Sharif et al. above, using the CRISPR/Cas targeted genome editing technique to make the process simple and efficient, as described by Chen et al., with the realistic goal to produce ovary-derived seedless fruits.
Before the effective filing date, an ordinarily skilled artisan would have been motivated to mutate an ortholog of ARF8A by introducing a mutation into the PB1 domain using the CRISPR/Cas targeted genome editing technique to make the process simple and efficient with the realistic goal to produce ovary-derived seedless fruits.
Regarding claim 37, Chen et al. describes cross breeding to improving a trait through crossing an elite recipient line with a donor line and selecting outstanding progeny with the desired trait. To introduce the desired trait from the donor line into the elite recipient line, the selected progeny must be backcrossed with the recipient line for several generations to eliminate unexpected linked traits (page 669, Fig. 1). The recipient line often is the elite parental line used for initial mutagenesis which can be a wild type plant of the same species. Crossing is also done to obtain transgene-free plants (page 676, para 4, line 7-8; Fig. 4).
Before the effective filing date of the invention, it would have been obvious to an ordinarily skilled artisan to cross the transgenic plants; as described by Goetz et al. and Guilfoyle, TJ. and as described above; with the parental wildtype plant of the same species to eliminate any unexpected linked trait and/or to obtain transgene-free plants, as described by Chen et al.
Before the effective filing date, an ordinarily skilled artisan would have been motivated to cross the transgenic plants; as described by Goetz et al. and Guilfoyle, TJ., and as described above; with the parental wildtype plant of the same species to eliminate any unexpected linked trait and/or to obtain transgene-free plants.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Goetz et al., as applied to claims 1-8, 10-13, 15-16, 19-23, 28-29 above, and further in view of Hu et al. (The Interaction between DELLA and ARF/IAA Mediates Crosstalk between Gibberellin and Auxin Signaling to Control Fruit Initiation in Tomato, 2018, The Plant Cell, 30:1710–1728).
Claim 24 depends from claim 1 and is drawn to the genetically modified flowering plant of claim 1, wherein fruit from the plant exhibits placental growth that is at least 80% of the placental growth exhibited by fruit from a wildtype plant of the same species.
Goetz et al. describes a genetically modified flowering plant that expresses a modified Auxin Response Factor 8A (ARF8A) or an ortholog thereof, wherein the modified ARF8A or an ortholog thereof comprises a mutation in a Phox and Beml (PB1) domain, and wherein the flowering produces ovary-derived, seedless fruit, as discussed above.
However, Goetz et al. does not describe placental growth.
Hu et al. teaches that a loss-of-function mutation in Arabidopsis ARF8, downregulation of the eggplant ARF8 (SmARF8) by RNAi, and even overexpression of SmARF8 in Arabidopsis also promotes parthenocarpy (page 1710, right column, last para, last 2 lines and page 1711, left column, first para, first 4 lines). Hu et al. also describes that (elected level of) Auxin increases fruit size by increasing the number of pericarp cell layers and enlarging the placenta (page 1711, left column, last para, line 26-27) and observed more developed placenta in many mutant lines including silencing ARF7 (an ortholog of ARF8A) with either entire (IAA9) or procera (della) mutants (page 1720, left column, last para, line 23-25). Silencing of ARF7 using RNAi in tomato itself confer parthenocarpy, similar to loss-of-function mutation in Arabidopsis and eggplant AFR8 (page 1710 right column, last para, last 2 lines; and page 1711, right column, first para, first 2 lines), while downregulating expression of multiple ARFs (abstract, line 9).
Before the effective filing date of the invention, it would have been obvious to an ordinarily skilled artisan to modify an orthologue of ARF8 including AFR7 (as described by Hu et al) and/or AFR8 itself (as described by Goetz et al.) with a realistic goal to produce ovary derived, seed-less, parthenocarpic fruit which would have more developed placenta, described by Hu et al. Enlarged and “more developed” placenta implies that the placental growth is more than 100% (reads on to “at least 80%”) of the placental growth exhibited by fruit from a wildtype plant, as recited in claim 24. This observation is also supported by the fact that auxin levels are elevated in the ovary of different mutant lines of SlARFs including ARF7 and ARF8 (Spec, page 10, para 0031) and elevated level of auxin increases fruit size by increasing the number of pericarp cell layers and enlarging the placenta, as described by Hu et al. (page 1711, left column, last para, line 26-27).
Before the effective filing date, one with ordinary skill in the art would have been motivated to mutate ARF8 and/or its orthologue ARF7 to produce ovary derived, seed-less, parthenocarpic fruit which would have more developed placenta that is at least 80% of the placental growth exhibited by fruit from a wildtype plant of the same species.
Conclusion
Claims 1-13, 15-17 and 19-37 are rejected.
Claims 14 and 18 are free of prior art rejection.
However, claims 14 and 18 are objected to as the base claims are rejected. The claims may be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Communication
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Jay Chatterjee
Patent Examiner
Art Unit 1662
/Jay Chatterjee/Examiner, Art Unit 1662
/BRATISLAV STANKOVIC/Supervisory Patent Examiner, Art Units 1661 & 1662