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 .
Status of the Claims
Claims 4, 6-8, 12, 15-18, 21-23, 25-31, 34-39, and 42-55 are canceled.
Claims 1-3, 5, 9-11, 13-14, 19-20, 24, 32-33, 40-41, and 56-58 are pending.
Claims 1-3, 5, 9-11, 13-14, 19-20, 24, 32-33, 40-41, and 56-58 are examined herein.
The previous objection to the claim 41 has been withdrawn in view of Applicant’s amendments to the claims.
The rejections to claims 1-3, 5, 9-11, 13-14, 19-20, 24, 32-33, and 40-41 under 35 USC § 112(a) have been withdrawn in view of Applicant’s amendments to the claims.
The rejections to claims 40-41 under 35 USC § 101 have been withdrawn in view of Applicant’s amendments to the claims.
Claims 1-3, 5, 9-11, 13-14, 19-20, 24, 32-33, 40-41, and 56-58 are rejected.
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, 3, 5, 9-11, 13-14, and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dunse (US-20070219147-A1).
Claim 1 is drawn to a plant, or a plant cell thereof, with enhanced resistance to at least one bacterial pathogen, the plant comprising a heterologous polynucleotide encoding a protease inhibitor protein having at least 95% sequence identity to at least one of the amino acid sequences set forth in SEQ ID NOs: 1-5.
Claim 3 is drawn to the plant cell of claim 1, wherein the polynucleotide is operably linked to a promoter functional in a plant cell.
Claim 5 is drawn to the plant of claim 1, wherein the at least one bacterial pathogen is of the family Pectobacteriaceae, or wherein the at least one bacterial pathogen causes a bacterial soft rot.
Claim 9 is drawn to the plant of claim 1, wherein the plant is a potato plant.
Claim 10 is drawn to a fruit, tuber, leaf, or seed of the plant of claim 1, wherein the fruit, tuber, leaf, or seed comprises the heterologous polynucleotide.
Claim 11 is drawn to a method of enhancing the resistance of a plant to at least one bacterial pathogen, the method comprising: modifying at least one plant cell to comprise a polynucleotide encoding a protease inhibitor protein having at least 95% sequence identity to at least one of the amino acid sequences set forth in SEQ ID NOs: 1-5.
Claim 13 is drawn to the method of claim 11, further comprising regenerating a plant comprising in its genome the polynucleotide from the plant cell.
Claim 14 is drawn to the method of claim 11, wherein modifying at least one plant cell to comprise the polynucleotide comprises (a) introducing a heterologous polynucleotide encoding the protease inhibitor protein into at least one plant cell, or (b) using genome editing to modify the nucleotide sequences of a native or non-native gene in the genome of the plant cell to comprise the polynucleotide encoding the protease inhibitor protein.
Claim 24 is drawn to the method of claim 11, wherein the plant is a potato plant.
Regarding claims 1 and 11, Dunse discloses an invention related to a chemotrypsin protein (HpF5) that is resistant to Nicotiana alta serine protease inhibitors (NaPI), and identification of protease inhibitors that are effective against the NaPI-insenesitive chemotrypsin (title, abstract, entire document). Specifically, Dunse discloses a genetically modified plant comprising a nucleic acid molecule encoding PotIA and/or PotIB, and teaches PotIB has over 97% sequence identity to instant SEQ ID NO: 3 (claim 61, Table 1, SEQ ID NO: 77 of Dunse) (see alignment below).
RESULT 1
US-10-554-237A-77
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
Sequence 77, US/10554237A
Publication No. US20070219147A1
GENERAL INFORMATION
APPLICANT: Hexima Limited
APPLICANT: La Trobe University
APPLICANT: Anderson, Marilyn, Anne (US ONLY)
APPLICANT: Heath, Robyn, Louise (US ONLY)
APPLICANT: Dunse, Kerry, Michelle (US ONLY)
TITLE OF INVENTION: Novel insect enzymes and inhibitors thereof
FILE REFERENCE: 12440340/EJH
CURRENT APPLICATION NUMBER: US/10/554,237A
CURRENT FILING DATE: 2005-10-21
PRIOR APPLICATION NUMBER: US 60/465,054
PRIOR FILING DATE: 2003-04-23
NUMBER OF SEQ ID NOS: 93
SEQ ID NO 77
LENGTH: 107
TYPE: PRT
ORGANISM: potato
Query Match 97.6%; Score 532; Length 107;
Best Local Similarity 97.2%;
Matches 104; Conservative 2; Mismatches 1; Indels 0; Gaps 0;
Qy 1 MESKFAHIIVFFLLATSFETLLARKESDGPEVIELLKEFECNGKQFWPELIGVPTKLAKE 60
|||||||||||||||||||||:||||||||||||||||||||||||||||||||||||||
Db 1 MESKFAHIIVFFLLATSFETLMARKESDGPEVIELLKEFECNGKQFWPELIGVPTKLAKE 60
Qy 61 IIEKENSLINNVQILLNGSPVTMDYRCDRVRLFDNILGDVVQIPRVA 107
|||||||||||||||||||||||||||:|||||||||| ||||||||
Db 61 IIEKENSLINNVQILLNGSPVTMDYRCNRVRLFDNILGSVVQIPRVA 107
Regarding claim 3, Dunse discloses genetically engineered plants overexpressing the PotI gene(s) are operably linked to a 35S promoter (¶0280).
Regarding claims 9 and 24, Dunse discloses the plant is potato (claim 59).
Regarding claim 10, Dunse discloses the plant is genetically engineered, which is interpreted as stably genetically engineered (supported by example 6, ¶0280-0281). Dunsen also discloses reference to a "plant" includes a monocotyledonous or dicotyledonous plant and may be a plant regenerated from genetically transformed callus or tissue or progeny of such a plant, and the present invention further provides seeds and other reproductive material from the genetically modified plants of the present invention (¶0032). Therefore all parts of the plant including , e.g. a leaf as claimed, would comprise the heterologous PotIB polynucleotide.
Regarding claim 13, Dunsen discloses reference to a "plant" includes a monocotyledonous or dicotyledonous plant and may be a plant regenerated from genetically transformed callus or tissue or progeny of such a plant (¶0032) (i.e. regenerating a plant that comprises in its genome the polynucleotide from the plant cell).
Regarding claim 14, Dunsen discloses the present invention provides nucleic acid molecules which encode potato-derived protenase inhibitors such as but not limited to Pot1A and Pot1B or their homologs or derivatives as well as transgenic plants comprising and capable of expressing same (¶0034). Dunsen further discloses reference to a "plant" includes a monocotyledonous or dicotyledonous plant and may be a plant regenerated from genetically transformed callus or tissue or progeny of such a plant (¶0032). Therefore, Dunsen discloses introducing a heterologous polynucleotide encoding the protease inhibitor protein into at least on plant cell.
The remaining limitation of claim 1 that is the plant has increased resistance to at least one bacteria pathogen is also anticipated because the function is inherent to the anticipated amino acid sequence. The instant specification provides evidence that the claimed amino acid sequences have antimicrobial activity including to Pectobacterium including when expressed in plants (spec., p. 54). Because Dunse discloses expressing an amino acid sequence with nearly 98% sequence identity to instant SEQ ID NO: 3 in a plant, the claimed amino acid sequence (and plant expressing the sequence) disclosed by Dunse would reasonably be interpreted to be capable of the same recited function, without evidence to the contrary.
Claims 5 and 20 are also anticipated because the functions are inherent to the anticipated amino acid sequence. Dunse discloses the limitations of claims 1 and 11 from which claims 5 and 20 depend. Claims 5 and 20 require wherein the at least one bacterial pathogen is of the family Pectobacteriaceae, or wherein the at least one bacterial pathogen causes a bacterial soft rot. The instant specification provides evidence that the claimed amino acid sequences have antimicrobial activity to the bacterial pathogen Pectobacterium including when expressed in plants (spec., p. 54). Because Dunse discloses expressing an amino acid sequence with nearly 98% sequence identity to instant SEQ ID NO: 3 in a plant, the claimed amino acid sequence (and plant expressing the sequence) disclosed by Dunse would reasonably be interpreted to be capable of the same recited function, especially without evidence to the contrary.
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.
Claims 19, 32-33, and 40-41 are rejected under 35 U.S.C. 103 as being unpatentable over Dunse (US-20070219147-A1).
Claim 19 is drawn to the method of claim 11, further comprising selecting for a plant or a plant cell having enhanced resistance to at least one bacterial pathogen as compared to a corresponding control plant or plant cell without the polynucleotide.
Claim 32 is drawn to a method of limiting a plant disease caused by at least one bacterial pathogen in agricultural crop production, the method comprising: planting a seedling, tuber, or seed of the plant of claim 1; and growing the seedling, tuber, or seed under conditions favorable for the growth and development of a plant resulting therefrom.
Claim 33 is drawn to the method of claim 32, further comprising harvesting at least one fruit, tuber, leaf and/or seed from the plant.
Claim 40 is drawn to a method for introducing at least one protease inhibitor gene into a plant, the method comprising: (a) crossing the plant of claim 1 with a second plant, whereby at least one progeny plant is produced; and (b) selecting at least one progeny plant comprising the heterologous polynucleotide encoding the protease inhibitor protein.
Claim 41 is drawn to the method of claim 40, wherein the plant is a potato.
Regarding claims 19, 32-33, and 40-41, Dunse teaches the limitations of claim 1 and 11 as set forth in the previous anticipation rejection. The teachings of Dunse as they are applied to claims 1 and 11 are set forth previously herein and are incorporated by reference.
However, Dunse does not further explicitly teach in a single embodiment the limitations of claims 19, 32-33, and 40-41 as recited above.
Regarding claim 19, in an alternative embodiment, Dunse teaches expressing PotIA (rather than PotIB) in transgenic cotton by transforming embryos, and teaches the transgenic callus were selected for on selective media (¶0281). It would be obvious to combine the alternative embodiments, thereby expressing PotIB in transgenic cotton by transforming embryos and selecting for the transgenic callus on selective media. By doing so, because the PotIB sequence is anticipated by Dunse and the function of increased resistance to at least one bacteria pathogen is inherent to the anticipated amino acid sequence (see below), the method of selecting for a plant or plant cell having enhanced resistance to at least one bacterial pathogen as compared to a corresponding control plant or plant cell without the polynucleotide is also obvious in view of Dunse.
Regarding claim 32, in an alternative embodiment, Dunse teaches expressing PotIA (rather than PotIB) in transgenic cotton by transforming embryos, and the germinated embryos with roots and true leaves (i.e. seedlings) were transferred to containers for further development and then transferred to soil and grown in a growth cabinet (i.e. planting a seedling of a plant of claim 1 and growing the seedling under conditions favorable for the growth and development of a plant resulting therefrom) (¶0281).
Regarding claim 33, Dunse further teaches the plant expressing PotIA was crossed to a plant expressing NaPI, and progeny seed expressing both genes was collected and identified (i.e. further comprising harvesting a seed from the plant) (¶0282).
Regarding claim 40, in an alternative embodiment, Dunse teaches expressing PotIA (rather than PotIB) in transgenic cotton by transforming embryos,, and the germinated embryos with roots and true leaves (i.e. seedlings) were transferred to containers for further development and then transferred to soil and grown in a growth cabinet (¶0281). Dunse further teaches the plant expressing PotIA was crossed to a plant expressing NaPI, and progeny seed expressing both genes was collected and identified (¶0282). Therefore, Dunse teaches in an alternative embodiment crossing a plant expressing PotIB with a second plant and producing progeny that comprises the heterologous polynucleotide encoding the protease inhibitor protein.
Regarding claim 41, Dunse teaches in the working example the plant is cotton, however teaches in an alternative embodiment the plant is potato (claim 59 of Dunse).
Dunse teaches all of the limitations of the rejected claims in alternative embodiments, but does not disclose a single embodiment having all the limitations. As such, the claims are not rejected as anticipated under 35 USC §102 but are instead rejected as obvious under 35 USC §103. One of ordinary skill in the art would have been motivated to combine the limitations as taught by Dunse into a single embodiment to arrive at Applicant’s claimed inventions because each limitation is explicitly taught as an alternative embodiment of the invention. It would therefore be obvious to combine the methods taught by Dunse for the purpose of producing a transgenic plant expressing PotIB (rather than PotIA) to inhibit the chemotrypsin described in Dunse’s disclosure, crossing the plant, and collecting the progeny comprising the nucleotide encoding the protease inhibitor as explicitly taught by Dunse (¶0281-0282). One having ordinary skill in the art would have a reasonable expectation of success because Dunse teaches both PotIA and PotIB effectively inhibit the chemotrypsin described in the disclosure of Dunse, and the method Dunse teaches was functional and successful and the application to the alternative embodiments present no special technical obstacles.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Dunse (US-20070219147-A1) as applied to claim 1, and further in view of NCBI GenBank Accession No. L06137.1 (NCBI GenBank Accession No. L06137.1, Solanum tuberosum proteinase inhibitor 1 (pin1) mRNA, complete cds, published online 07/12/1995).
Claim 2 is drawn to the plant of claim 1, wherein the polynucleotide encoding the protease inhibitor protein has at least 95% sequence identity to at least one of the nucleotide sequences set forth in SEQ ID NOs: 6-15.
Regarding claim 2, Dunse teaches the limitations of claim 1 as set forth in the previous anticipation rejection. The teachings of Dusne as they are applied to claim 1 are set forth previously herein and are incorporated by reference.
However, Dunse does not explicitly teach the limitations of claim 2 as recited above.
In analogous art, NCBI GenBank Accession No. L06137.1 teaches a nucleotide sequence encoding a Solanum tuberosum-derived proteinase inhibitor 1 protein that has over 99% sequence identity to instant SEQ ID NO: 8 (title, see alignment below).
PNG
media_image1.png
517
817
media_image1.png
Greyscale
It would therefore have been obvious to a person of ordinary skill in the art to
modify the invention of as taught by Dunse to include the proteinase inhibitor I nucleotide sequence taught by NCBI GenBank Accession No. L06137.1 to arrive at the instantly claimed method with a reasonable expectation of success because it was a known and readily obtainable sequence. One having ordinary skill in the art would have been motivated to combine the teachings because it would have been prima facie obvious to back-translate the amino acid sequence taught by Dunse using a public domain (e.g., NCBI blast) to obtain a readily available nucleotide sequence that has high sequence identity encoding the amino acid sequence of Dunse. By doing so, one of ordinary skill would arrive at the nucleotide sequence of NCBI GenBank Accession No. L06137.1 which has over 99% sequence identity to instant SEQ ID NO: 8.
Claims 56-57 are rejected under 35 U.S.C. 103 as being unpatentable over Dunse (US-20070219147-A1) as applied to claim 1, and further in view of Uniprot Accession No. Q43651 (Uniprot Accession No. Q43651, Proteinase inhibitor 1 (pin1), Solanum tuberosum, published online 11/01/1996) and as evidenced by Hernandez (Hernández, G., Osnaya, V. G., & Pérez-Martínez, X. (2019). Conservation and variability of the AUG initiation codon context in eukaryotes. Trends in biochemical sciences, 44(12), 1009-1021).
Claim 56 is drawn to the plant of claim 1, wherein the polynucleotide encodes a protease inhibitor protein having at least 98% sequence identity to at least one of the amino acid sequences set forth in SEQ ID NOs: 1-5.
Claim 57 is drawn to the plant of claim 1, wherein the polynucleotide encodes a protease inhibitor protein having at least 99% sequence identity to at least one of the amino acid sequences set forth in SEQ ID NOs: 1-5.
Regarding claims 56-57, Dunse teaches the limitations of claim 1 as set forth in the previous anticipation rejection. The teachings of Dusne as they are applied to claim 1 are set forth previously herein and are incorporated by reference.
However, Dunse does not explicitly teach the limitations of claims 56-57 as recited above.
Regarding claim 56, in analogous art, Uniprot Accession No. Q43651 teaches a solanum tuberosum derived proteinase inhibitor 1 (pot1) amino acid sequence that has over 98% sequence identity to instant SEQ ID NO: 3 (see alignment below).
Regarding claim 57, the amino acid sequence of Uniprot Accession No. Q43651 has 105 matches of 107 amino acids that are present in the sequence of SEQ ID NO: 3. This is because the sequence of Uniprot Accession No. Q43651 does not include a methionine encoded by a start codon. However, a start codon encoding a methionine amino acid at the beginning of the sequence initiates translation of the protein of interest as evidenced by Hernandez, 2019 (see title, abstract, entire document, and initiation odcon definition on p. 1010 right column). Therefore, it would be obvious to include a methionine at the beginning of the sequence which would result in 106/107 matching amino acids, or the sequence of Uniprot Accession No. Q43651 including the methionine having over 99% sequence identity to instant SEQ ID NO: 3.
RESULT 1
Q43651_SOLTU
ID Q43651_SOLTU Unreviewed; 106 AA.
AC Q43651;
DT 01-NOV-1996, integrated into UniProtKB/TrEMBL.
DT 01-NOV-1996, sequence version 1.
DT 05-FEB-2025, entry version 68.
DE SubName: Full=Proteinase inhibitor I {ECO:0000313|EMBL:AAA72133.1};
DE Flags: Fragment;
GN Name=pin1 {ECO:0000313|EMBL:AAA72133.1};
OS Solanum tuberosum (Potato).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; lamiids; Solanales; Solanaceae; Solanoideae; Solaneae; Solanum.
OX NCBI_TaxID=4113 {ECO:0000313|EMBL:AAA72133.1};
RN [1] {ECO:0000313|EMBL:AAA72133.1}
RP NUCLEOTIDE SEQUENCE.
RC TISSUE=Tuber {ECO:0000313|EMBL:AAA72133.1};
RX PubMed=7807552; DOI=10.1007/BF00160410;
RA Beuning L.L., Spriggs T.W., Christeller J.T.;
RT "Evolution of the proteinase inhibitor I family and apparent lack of
RT hypervariability in the proteinase contact loop.";
RL J. Mol. Evol. 39:644-654(1994).
CC -!- SIMILARITY: Belongs to the protease inhibitor I13 (potato type I serine
CC protease inhibitor) family. {ECO:0000256|ARBA:ARBA00008210}.
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DR EMBL; L06985; AAA72133.1; -; mRNA.
DR AlphaFoldDB; Q43651; -.
DR MEROPS; I13.006; -.
DR ExpressionAtlas; Q43651; baseline and differential.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0009611; P:response to wounding; IEA:InterPro.
DR Gene3D; 3.30.10.10; Trypsin Inhibitor V, subunit A; 1.
DR InterPro; IPR000864; Prot_inh_pot1.
DR InterPro; IPR036354; Prot_inh_pot1_sf.
DR PANTHER; PTHR33091; PROTEIN, PUTATIVE, EXPRESSED-RELATED; 1.
DR PANTHER; PTHR33091:SF65; WOUND-INDUCED PROTEINASE INHIBITOR 1; 1.
DR Pfam; PF00280; potato_inhibit; 1.
DR PRINTS; PR00292; POTATOINHBTR.
DR SUPFAM; SSF54654; CI-2 family of serine protease inhibitors; 1.
DR PROSITE; PS00285; POTATO_INHIBITOR; 1.
PE 2: Evidence at transcript level;
KW Protease inhibitor {ECO:0000256|ARBA:ARBA00022690};
KW Serine protease inhibitor {ECO:0000256|ARBA:ARBA00022900};
KW Signal {ECO:0000256|SAM:SignalP}.
FT SIGNAL 1..22
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 23..106
FT /evidence="ECO:0000256|SAM:SignalP"
FT /id="PRO_5004231986"
FT NON_TER 1
FT /evidence="ECO:0000313|EMBL:AAA72133.1"
SQ SEQUENCE 106 AA; 12075 MW; 0CB4A72602D2B4E2 CRC64;
Query Match 98.2%; Score 535; Length 106;
Best Local Similarity 99.1%;
Matches 105; Conservative 1; Mismatches 0; Indels 0; Gaps 0;
Qy 2 ESKFAHIIVFFLLATSFETLLARKESDGPEVIELLKEFECNGKQFWPELIGVPTKLAKEI 61
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ESKFAHIIVFFLLATSFETLLARKESDGPEVIELLKEFECNGKQFWPELIGVPTKLAKEI 60
Qy 62 IEKENSLINNVQILLNGSPVTMDYRCDRVRLFDNILGDVVQIPRVA 107
||||||||||||||||||||||||||:|||||||||||||||||||
Db 61 IEKENSLINNVQILLNGSPVTMDYRCNRVRLFDNILGDVVQIPRVA 106
It would therefore have been obvious to a person of ordinary skill in the art to
modify the invention of as taught by Dunse to include the potato-derived proteinase inhibitor 1 (Pot1) amino acid sequence taught by Uniprot Accession No. Q43651 to arrive at the instantly claimed method with a reasonable expectation of success because the Pot1 amino acid sequence taught by Uniprot Accession No. Q43651 was a known and readily obtainable sequence. One having ordinary skill in the art would have been motivated to combine the teachings because it would have been prima facie obvious to substitute the Pot1 protein taught by Dunse with another Pot1 protein known in the art, Uniprot Accession No. Q43651, for the same purpose.
Claim 1 and 58 are rejected under 35 U.S.C. 103 as being unpatentable over Imai (JP-2007049922-A) and Uniprot Accession No. A0A0V0HDC8 (Uniprot Accession No. A0A0V0HDC8, Putative cysteine protease inhibitor 9-like, Solanum tuberosum, version 10, published online 08/12/2020).
Claim 1 is drawn to a plant, or a plant cell thereof, with enhanced resistance to at least one bacterial pathogen, the plant comprising a heterologous polynucleotide encoding a protease inhibitor protein having at least 95% sequence identity to at least one of the amino acid sequences set forth in SEQ ID NOs: 1-5.
Claim 58 is drawn to the plant of claim 1, wherein the polynucleotide encodes a protease inhibitor protein having at least one of the amino acid sequences set forth in SEQ ID NOs: 1-5.
Regarding claim 1, Imai teaches the protective function of cystatin against pests and pathogens, including bacteria, has been proved by transgenic plants overexpressing cysteine protease inhibitors (abstract, background ¶1).
However, Imai does not explicitly teach the remaining limitation of claim 1 that is the protease inhibitor has an amino acid sequence with 95% sequence identity to instant SEQ ID NO: 1, nor the limitations of claim 58 that is the protease inhibitor has an amino acid sequence with 100% sequence identity to instant SEQ ID NO: 1
Regarding claims 1 and 58, in analogous art, Uniprot Accession No. A0A0V0HDC8 teaches an amino acid sequence of a cysteine protease inhibitor that is 100% identical to instant SEQ ID NO: 1 (see alignment below).
RESULT 1
A0A0V0HDC8_SOLCH
ID A0A0V0HDC8_SOLCH Unreviewed; 222 AA.
AC A0A0V0HDC8;
DT 16-MAR-2016, integrated into UniProtKB/TrEMBL.
DT 16-MAR-2016, sequence version 1.
DT 05-FEB-2025, entry version 17.
DE SubName: Full=Putative cysteine protease inhibitor 9-like {ECO:0000313|EMBL:JAP18367.1};
OS Solanum chacoense (Chaco potato).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; lamiids; Solanales; Solanaceae; Solanoideae; Solaneae; Solanum.
OX NCBI_TaxID=4108 {ECO:0000313|EMBL:JAP18367.1};
RN [1] {ECO:0000313|EMBL:JAP18367.1}
RP NUCLEOTIDE SEQUENCE.
RA Liu Y., Joly V., Sabar M., Matton D.P.;
RT "Gene expression during late stages of embryo sac development: a critical
RT building block for successful pollen-pistil interactions.";
RL Submitted (DEC-2015) to the EMBL/GenBank/DDBJ databases.
CC -!- SUBCELLULAR LOCATION: Vacuole {ECO:0000256|ARBA:ARBA00004116}.
CC -!- SIMILARITY: Belongs to the protease inhibitor I3 (leguminous Kunitz-
CC type inhibitor) family. {ECO:0000256|ARBA:ARBA00005440}.
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DR EMBL; GEDG01021368; JAP18367.1; -; Transcribed_RNA.
DR AlphaFoldDB; A0A0V0HDC8; -.
DR GO; GO:0005773; C:vacuole; IEA:UniProtKB-SubCell.
DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR CDD; cd00178; STI; 1.
DR Gene3D; 2.80.10.50; -; 1.
DR InterPro; IPR011065; Kunitz_inhibitor_STI-like_sf.
DR InterPro; IPR002160; Prot_inh_Kunz-lg.
DR PANTHER; PTHR33107:SF44; CYSTEINE PROTEASE INHIBITOR 1; 1.
DR PANTHER; PTHR33107; KUNITZ TRYPSIN INHIBITOR 2; 1.
DR Pfam; PF00197; Kunitz_legume; 1.
DR SMART; SM00452; STI; 1.
DR SUPFAM; SSF50386; STI-like; 1.
DR PROSITE; PS00283; SOYBEAN_KUNITZ; 1.
PE 3: Inferred from homology;
KW Protease inhibitor {ECO:0000256|ARBA:ARBA00022690};
KW Signal {ECO:0000256|SAM:SignalP};
KW Thiol protease inhibitor {ECO:0000256|ARBA:ARBA00022704};
KW Vacuole {ECO:0000256|ARBA:ARBA00022554}.
FT SIGNAL 1..22
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 23..222
FT /evidence="ECO:0000256|SAM:SignalP"
FT /id="PRO_5006865818"
SQ SEQUENCE 222 AA; 24797 MW; 310E43AD0F8241EB CRC64;
Query Match 100.0%; Score 699; Length 222;
Best Local Similarity 100.0%;
Matches 131; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MSIPQFLGEGTPVKFVRKSESDYGDVVRVMTGVYIKFFVKTTKLCVDQTVWKVNHEGLVV 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 92 MSIPQFLGEGTPVKFVRKSESDYGDVVRVMTGVYIKFFVKTTKLCVDQTVWKVNHEGLVV 151
Qy 61 TGGQVGNENDIFKIRKTDLVTPEGSKFVYKLLHCPSHLQCKNIGGNFKNGYPRLVTVDDE 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 152 TGGQVGNENDIFKIRKTDLVTPEGSKFVYKLLHCPSHLQCKNIGGNFKNGYPRLVTVDDE 211
Qy 121 KDFLPFVFIKA 131
|||||||||||
Db 212 KDFLPFVFIKA 222
It would therefore have been obvious to a person of ordinary skill in the art to
modify the invention of as taught by Imia to include the amino acid sequence taught by Uniprot Accession No. A0A0V0HDC8 to arrive at the instantly claimed method with a reasonable expectation of success because ABCDE taught by Uniprot Accession No. A0A0V0HDC8 was a known and readily obtainable sequence. One having ordinary skill in the art would have been motivated to combine the teachings because it would have been prima facie obvious to substitute the cysteine protease inhibitor protein taught by Imia with another cysteine protease inhibitor protein known in the art, Uniprot Accession No. A0A0V0HDC8, for the same purpose.
Closest Prior Art
Claim 1 with respect to elected SEQ ID NO: 5 appears free of the prior art.
Regarding claim 1 with respect to elected SEQ ID NO: 5, the closest prior art is Uniprot Accession No. M1DYZ2 (Uniprot Accession No. M1DYZ2, Miraculin, Solanum tuberosum, published online 10/07/2020). Uniprot Accession No. M1DYZ2 teaches an amino acid sequence of a proteinase inhibitor that has 89.4% sequence identity to instant SEQ ID NO: 5. That is, a protease inhibitor protein comprising an amino acid sequence that has 95% identity to SEQ ID NO: 5 does not appear in the prior art, and therefore there is no teaching, suggesting, or motivation to express an amino acid sequence that has 95% identity to SEQ ID NO: 5 in a plant.
Claim 58 appears free of the prior art with respect to SEQ ID NOs: 2-5.
Regarding claim 58 with respect to SEQ ID NOs: 2-5, the closest prior art is Dunse (US-20070219147-A1). Dunse discloses an invention related to a chemotrypsin protein (HpF5) that is resistant to Nicotiana alta serine protease inhibitors (NaPI), and identification of protease inhibitors that are effective against the NaPI-insenesitive chemotrypsin (title, abstract, entire document). Specifically, Dunse discloses a genetically modified plant comprising a nucleic acid molecule encoding PotIA and/or PotIB, and teaches PotIB has over 97% sequence identity to instant SEQ ID NO: 3 (claim 61, Table 1, SEQ ID NO: 77 of Dunse) (see alignment below). Other PotI sequences up to 99% identical appear in the prior art. However, Dunse does not disclose, teach, or otherwise render obvious wherein the polynucleotide encodes a protease inhibitor protein having the amino acid sequence set forth in SEQ ID NO: 3 (i.e. claim 58). That is, a protease inhibitor protein comprising an amino acid sequence that has 100% identity to SEQ ID NO: 3 does not appear in the prior art. Therefore, there is no teaching, suggesting, or motivation to express an amino acid sequence that has 100% identity to SEQ ID NO: 3 in a plant.
Additionally, a protease inhibitor protein comprising an amino acid sequence that has 100% identity to SEQ ID NOs: 2 and 4-5 does not appear in the prior art. Therefore, there is no teaching, suggesting, or motivation to express an amino acid sequence that has 100% identity to SEQ ID NOs: 2 and 4-5 in a plant.
Response to Arguments
Applicant argues beginning on p. 8 of remarks dated 12/31/2025 the
following arguments:
Claims 1, 3, 10, 11, 13, 14, 19, 32, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Dunse (Dunse, K. M., Stevens, J. A., Lay, F. T., Gaspar, Y. M., Heath, R. L., & Anderson, M. A. (2010). Coexpression of potato type I and II proteinase inhibitors gives cotton plants protection against insect damage in the field. Proceedings of the National Academy of Sciences, 107(34), 15011-15015), Kim (Kim, J. Y., Park, S. C., Hwang, I., Cheong, H., Nah, J. W., Hahm, K. S., & Park, Y. (2009). Protease inhibitors from plants with antimicrobial activity. International journal of molecular sciences, 10(6), 2860-2872) and UniProt Accession No. A0A0V0HDC8 (version 10, published online 08/12/2020).
Dunse is said to teach expressing a heterologous potato-derived protease inhibitor in plants and modifying at least one plant cell to comprise a polynucleotide encoding a protease inhibitor protein. More specifically, Dunse discloses a Solanum tuberosum potato type I serine protease inhibitor (StPin1A) that reduced insect damage when expressed in cotton plants. Notably, Dunse relates to enhancing resistance to insects, not enhancing resistance to a bacterial pathogen as required by the present claims.
The Office Action further relies on Kim for teaching plant protease inhibitors with antimicrobial activity. Kim describes two protease inhibitors isolated from potato (Solanum tuberosum) tubers, namely potide-G and potamin-1. Kim reports that potide-G inhibited growth of various bacteria (including Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Clavibacter michiganense subsp. michiganense) and fungi (including Candida albicans and Rhizoctonia solani), and that potamin-1 inhibited several pathogenic microbial strains (including Candida albicans, Rhizoctonia solani, and Clavibacter michiganense subsp. michiganense).
Applicant respectfully submits that the cited references do not provide a person of ordinary skill in the art the requisite guidance, motivation, or expectation of success necessary to support an obviousness rejection. Even assuming, arguendo, that protease inhibitors as a broad class were known and that heterologous expression of certain protease inhibitors in plants had been performed (e.g., as in Dunse), the rejection still must articulate why a person of ordinary skill would have been led to select the specific protease inhibitor proteins recited in the claims (i.e., having at least 95% sequence identity to one of SEQ ID NOs: 1-5), with a reasonable expectation that doing so would confer enhanced resistance to at least one bacterial pathogen in a plant.
Aside from potide-G and potamin-1, Kim does not report any additional specific potato protease inhibitors that were tested for antibacterial activity. Moreover, it is clearly not the case that every known plant or potato protease inhibitor would be expected to enhance resistance to a bacterial pathogen when expressed in a plant. Protease inhibitors constitute a large and functionally diverse class of proteins, and the cited art provides no basis to treat them as interchangeable with respect to bacterial disease resistance in plants. Absent specific guidance or motivation in the prior art, the Office Action's reliance on the sequence of UniProt Accession No. A0A0V0HDC8 amounts to an arbitrary selection from among countless known plant or potato protease inhibitor sequences and constitutes impermissible hindsight reconstruction. For at least these reasons, there is no prima facie case of obviousness.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Dunse, Kim, and UniProt Accession No. AOAOVOHDC8 as applied to claim 1, and further in view of GenBank Accession No. X56874 (X56874, version X56874.1 published online 05/05/1995). Claims 5, 9, 20, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Dunse, Kim, and UniProt Accession No. AOAOVOHDC8 as applied to claims 1 and 11 and further in view of Lim (WO- 2011002126-A1).
GenBank Accession No. X56874 and Lim are further cited for teachings related to
dependent claims 2, 5, 9, 20, and 24. However, GenBank Accession No. X56874 and Lim fail to remedy the aforementioned deficiencies of Dunse, Kim, and UniProt Accession No. AOAOVOHDC8 in establishing obviousness of the independent claim from which these claims depend. As noted by the MPEP, "if an independent claim is nonobvious under 35 U.S.C. § 103, then any claim depending therefrom is nonobvious." (MPEP § 2143.03 citing In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988)).
Claims 40 and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Dunse, UniProt Accession No. AOAOVOHDC8, Oppenheimer (Oppenheimer, H. C. (1933). Cytogenetic investigations on tuber-bearing hybrids of Solanum species, I Solanum chacoense Bitt. x Solanum tuberosum L. s. str.), and Kim.
Claim 40 has been amended to refer to the plant of claim 1, and therefore, Applicant
respectfully submits that this rejection is also overcome for at least the reasons discussed above.
Reconsideration and withdrawal of the rejections of the claims under 35 U.S.C. § 103 are respectfully requested.
This argument has been fully considered and is found not persuasive for
the following reason(s):
In view of Applicant’s amendments and Applicant’s arguments, the claims are now rejected under modified 102 or 103 rejections (see above).
Conclusion
No claims are allowed.
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JESSICA N. STOCKDALE
Examiner
Art Unit 1663
/JESSICA NICOLE STOCKDALE/Examiner, Art Unit 1663
/CHARLES LOGSDON/Primary Examiner, Art Unit 1662
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