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 1-3, 8-11, 14, 16, 20, 23, 26, 71, 74-75, 80, 92-93 and 126-128 are pending.
Claims 1-3, 8-11, 14, 16, 20, 23, 26, 71, 74-75, 80, and 92 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected groups, there being no allowable generic or linking claim.
Newly added claim 128 reads on the elected invention and species and is thus examined herein.
Claims 93 and 126-128 are examined to the extent that they read on the elected species (i.e. the product of Group III; SEQ ID NOs: 69, 71, 75-89, and 95).
Examiner notes that in the previous Office action, claim 11 was not included among the pending claims. Examiner thanks the Applicant’s agent for identifying this error and apologizes for any confusion.
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 93 and 126-127 remain rejected and new claim 128 is rejected under 35 U.S.C. 103 as being unpatentable over Bull et al (2017, Nature Communications 8:936, pages 1-9) in view of NCBI Accession PWZ52556.1 (2018, ncbi.nlm.nih.gov/protein/PWZ52556.1) and Gao et al (2020, Nature Biotechnology 38: 579-581). Due to Applicant' s amendment of the claims, the rejection is modified from the rejection set forth in the previous Office action, mailed 17 November 2025. Applicant' s arguments filed 3 Feb 2026 have been fully considered but they are not persuasive.
The claims are broadly drawn to a guide nucleic acid that binds to a target site within histone demethylase gene that encodes an amino acid sequence with at least 80% identity SEQ ID NO: 71 (claim 93), wherein the target site is in a region of the gene having at least 90% identity to at least one of SEQ IDs: 75-86. The guide nucleic acid of claim 93, wherein said histone demethylase gene has a) a JmjN domain encoding an amino acid sequence with at least 80% to SEQ ID NO: 87; b) a Jmjc domain encoding an amino acid sequence with at least 80% to SEQ ID NO: 88; and/or c) a ZnF domain encoding an amino acid sequence with at least 80% to SEQ ID NO: 89 (claim 126). The guide nucleic acid of claim 93, wherein the guide nucleic acid comprises a spacer having the nucleotide sequence of SEQ ID NO: 95 (claim 127). The guide nucleic acid of claim 93 wherein the target site is in a region with at least 90% identity to any one of SEQ ID NOs: 75, 78, 81 or 84.
Bull et al 2017 teaches a barley Jumonji C-type H3K9me2/me3 demethylase (VRS3) whose loss of function is associated with gains in later spikelet fertility and that when mutant vrs3 alleles are combined with natural six-rowed barley alleles the result is an increase in lateral grain size (i.e. an increase in yield) and uniformity (page 2, column 2, paragraph 1; page 6, column 1, paragraph 2). Bull et al teaches that VRS3 had conserved synteny with OsJMJ706, a Jumonji C-type H3K9me2/me3 demethylase gene in rice, and that VRS3, also called HvJMJ706 is likely a functional ortholog of OsJMJ706 (page 2, column 2, paragraph 3). Bull et al teaches that VRS3/ HvJMJ706 comprises frame shift mutations in the zinc finger and JmjN functional domains, suggesting that VRS3/ HvJMJ706 may represent vrs3 loss of function mutants.
Bull et al does not teach a guide nucleic acid that binds to histone demethylase gene that encodes an amino acid sequence with at least 80% identity SEQ ID NO: 71. Bull et al does not teach a histone demethylase gene that has a) a JmjN domain encoded by a nucleic acid with at least 80% identity to SEQ ID NO: 75 or encoding an amino acid sequence with at least 80% to SEQ ID NO: 87; b) a JmjC domain encoded by a nucleic acid with at least 80% identity to SEQ ID NO: 76 or encoding an amino acid sequence with at least 80% to SEQ ID NO: 88; and/or c) a ZnF domain encoded by a nucleic acid with at least 80% identity to SEQ ID NO: 77 or encoding an amino acid sequence with at least 80% to SEQ ID NO: 89. Bull does not teach a nucleic acid that comprises a spacer having the nucleotide sequence of SEQ ID NO: 95.
NCBI Accession PWZ52556.1 teaches an amino acid sequence with 100% identity to SEQ ID NO: 71. NCBI Accession PWZ52556.1 teaches that said amino acid sequence is a maize Lysine-specific demethylase JMJ706, which comprises a JmjN domain, JmjC domain and ZnF domain (a C5HC2 zinc finger domain) and gives the positions of said domain.
Alignment of NCBI Accession PWZ52556.1 and SEQ ID NO: 71:
Score:1803 bits(4669), Expect:0.0,
Method:Compositional matrix adjust.,
Identities:861/861(100%), Positives:861/861(100%), Gaps:0/861(0%)
Query 1 MVEGRSYLPAEVRNGLETLKRRRLERVRLSAQNEAGDNPAVAARSGGDALRSPANCGVRL 60
MVEGRSYLPAEVRNGLETLKRRRLERVRLSAQNEAGDNPAVAARSGGDALRSPANCGVRL
Sbjct 1 MVEGRSYLPAEVRNGLETLKRRRLERVRLSAQNEAGDNPAVAARSGGDALRSPANCGVRL 60
Query 61 HSNNSTGLPGNVHDKSPFAKRKVEKFDMSNLEWIDKIPECPVYCPTKEEFEDPIAYIQKI 120
HSNNSTGLPGNVHDKSPFAKRKVEKFDMSNLEWIDKIPECPVYCPTKEEFEDPIAYIQKI
Sbjct 61 HSNNSTGLPGNVHDKSPFAKRKVEKFDMSNLEWIDKIPECPVYCPTKEEFEDPIAYIQKI 120
Query 121 SPEAAKYGICKIVSPVCASVPAGVVLMKEHPNFKFMTRVQPLRLAEWAEDDTVTFFMSGR 180
SPEAAKYGICKIVSPVCASVPAGVVLMKEHPNFKFMTRVQPLRLAEWAEDDTVTFFMSGR
Sbjct 121 SPEAAKYGICKIVSPVCASVPAGVVLMKEHPNFKFMTRVQPLRLAEWAEDDTVTFFMSGR 180
Query 181 KYTFRDYEKMANKVFSKKYSSSSCLPARYVEEEFWREIAFGKMDFVEYACDVDGSAFSSS 240
KYTFRDYEKMANKVFSKKYSSSSCLPARYVEEEFWREIAFGKMDFVEYACDVDGSAFSSS
Sbjct 181 KYTFRDYEKMANKVFSKKYSSSSCLPARYVEEEFWREIAFGKMDFVEYACDVDGSAFSSS 240
Query 241 PHDQLGKSNWNLKNFSWLPNSVLRLLQTPIPGVTDPMLYIGMLFSMFAWHVEDHYLYSIN 300
PHDQLGKSNWNLKNFSWLPNSVLRLLQTPIPGVTDPMLYIGMLFSMFAWHVEDHYLYSIN
Sbjct 241 PHDQLGKSNWNLKNFSWLPNSVLRLLQTPIPGVTDPMLYIGMLFSMFAWHVEDHYLYSIN 300
Query 301 YHHCGAFKTWYGIPGDAAPGFERVASQYVYNKDILIGDGEDAAFDVLLGKTTMFPPNVLL 360
YHHCGAFKTWYGIPGDAAPGFERVASQYVYNKDILIGDGEDAAFDVLLGKTTMFPPNVLL
Sbjct 301 YHHCGAFKTWYGIPGDAAPGFERVASQYVYNKDILIGDGEDAAFDVLLGKTTMFPPNVLL 360
Query 361 DHNVPVYKAVQRPGEFVITFPRSYHAGFSHGFNCGEAVNFAIGDWFPLGSLASKRYALLN 420
DHNVPVYKAVQRPGEFVITFPRSYHAGFSHGFNCGEAVNFAIGDWFPLGSLASKRYALLN
Sbjct 361 DHNVPVYKAVQRPGEFVITFPRSYHAGFSHGFNCGEAVNFAIGDWFPLGSLASKRYALLN 420
Query 421 RTPLLAHEELLCRSAVLLSQKLLNCDPRSLDKLEHPYSQNCVKSCFVRLIRFQRRARGLL 480
RTPLLAHEELLCRSAVLLSQKLLNCDPRSLDKLEHPYSQNCVKSCFVRLIRFQRRARGLL
Sbjct 421 RTPLLAHEELLCRSAVLLSQKLLNCDPRSLDKLEHPYSQNCVKSCFVRLIRFQRRARGLL 480
Query 481 AKMGSEICYKPKTFPNLSCSICRRDCYITHVLCRCNFDPVCLHHEQELRSCPCKSNRVVY 540
AKMGSEICYKPKTFPNLSCSICRRDCYITHVLCRCNFDPVCLHHEQELRSCPCKSNRVVY
Sbjct 481 AKMGSEICYKPKTFPNLSCSICRRDCYITHVLCRCNFDPVCLHHEQELRSCPCKSNRVVY 540
Query 541 VREDILELEALSRKFEQDVSSYKEGSCISPCKEVEISDTTDEQLPNLGITLDFVNSKAGS 600
VREDILELEALSRKFEQDVSSYKEGSCISPCKEVEISDTTDEQLPNLGITLDFVNSKAGS
Sbjct 541 VREDILELEALSRKFEQDVSSYKEGSCISPCKEVEISDTTDEQLPNLGITLDFVNSKAGS 600
Query 601 SGFMTVDGGNSSSAVSILTSSVHHEAYKHTEARVHATQSNHIYSIAKQAINTSMTKGTYT 660
SGFMTVDGGNSSSAVSILTSSVHHEAYKHTEARVHATQSNHIYSIAKQAINTSMTKGTYT
Sbjct 601 SGFMTVDGGNSSSAVSILTSSVHHEAYKHTEARVHATQSNHIYSIAKQAINTSMTKGTYT 660
Query 661 MDESSSGIDGACNEHGSCNASAMECSDNSDSECEIFRVKRRSTSFDKPTSEAKTSTLSEQ 720
MDESSSGIDGACNEHGSCNASAMECSDNSDSECEIFRVKRRSTSFDKPTSEAKTSTLSEQ
Sbjct 661 MDESSSGIDGACNEHGSCNASAMECSDNSDSECEIFRVKRRSTSFDKPTSEAKTSTLSEQ 720
Query 721 QVLRRLKKVHPEVQQVISKRQEESGNGSVRAAHMSQKSSNPAPADDETEDMAPIMWRIKR 780
QVLRRLKKVHPEVQQVISKRQEESGNGSVRAAHMSQKSSNPAPADDETEDMAPIMWRIKR
Sbjct 721 QVLRRLKKVHPEVQQVISKRQEESGNGSVRAAHMSQKSSNPAPADDETEDMAPIMWRIKR 780
Query 781 RQSETQDATCPGTRPQSYPPSSGGSGEEFVERTRDAAVELRPKRVKIRLPSNASRQIEQQ 840
RQSETQDATCPGTRPQSYPPSSGGSGEEFVERTRDAAVELRPKRVKIRLPSNASRQIEQQ
Sbjct 781 RQSETQDATCPGTRPQSYPPSSGGSGEEFVERTRDAAVELRPKRVKIRLPSNASRQIEQQ 840
Query 841 RSSGQRFAREDRLPLGFPRTF 861
RSSGQRFAREDRLPLGFPRTF
Sbjct 841 RSSGQRFAREDRLPLGFPRTF 861
Given the evidence provided in NCBI Accession PWZ52556.1 (i.e. the identification of the polypeptide as JMJ706 and the identification of the domain) and Applicant’s own teachings that SEQ ID NO: 71 is a Jumonji C-type H3K9me2/me3 demethylase also known as maize VRS3 (page 50, lines 13-32) the preponderance of evidence is that NCBI Accession PWZ52556.1 is a homolog of barley VRS3/HvJMJ706.
Gao et al teaches waxy corn hybrids with improved yield created by Crispr-Cas9 editing to generate deletions in the Waxy gene (page 579, column 1, first paragraph, last paragraph). Gao et al teaches plasmids comprising guide nucleic acids (sgRNA; 1st paragraph under “Methods”, unnumbered page following p. 581).
At the time of filing, it would have been obvious to one of ordinary skill in the art to make a guide nucleic acid that binds to a histone demethylase gene that encodes an amino acid sequence with at least 80% identity SEQ ID NO: 71, given that Bull et al teaches loss of function mutants of a Jumonji C-type H3K9me2/me3 demethylase (VRS3) in barley plants leads to increased grain size, given that NCBI Accession PWZ52556.1 teaches the maize homolog of Jumonji C-type H3K9me2/me3 demethylase (VRS3) and given that Gao et al teaches a method of using a guide nucleic acid to improve yield in a maize plant. One of ordinary skill would be motivated to do so given that increased grain size is a desirable trait in maize. One of ordinary skill would have had a reasonable expectation of success given the teachings of Gao et al which describe using guide nucleic acids in maize genome editing and given the teachings of Bull et regarding both the improved grain size of VRS3 loss of function mutants and the location of the deleterious frame shift mutations in the JmjN domain.
Regarding claims 93, 126, and 128 as SEQ ID NO: 71 comprises all the recited domains, so too will a polypeptide with 100% sequence identity to SEQ ID NO: 71, i.e. NCBI Accession PWZ52556.1. It would be obvious to target the JmjN domain present in the region of SEQ ID NO: 75 to generate modification which decrease or knock-out the function of a gene encoding a polypeptide with at least 80% sequence identity to SEQ ID NO: 71 given the additional teachings of Bull et al that describe the barley VRS3 loss of function mutants as comprising a frameshift mutation in the JmjN domain. Regarding claim 127, at the time of filing it would have been further obvious to one of ordinary skill in the art to make a guide nucleic acid which comprises the spacer of SEQ ID NO: 95, given the additional teachings of Bull et al that describe the barley VRS3 loss of function mutants as comprising a frameshift mutation in the JmjN domain, which is the target of SEQ ID NO: 95, based on an alignment of SEQ ID NO: 95 to SEQ ID NO:75, the claimed JmjN domain. Given that there are only a finite number of targets in the JmjN domain, it would have been obvious to a person of ordinary skill in the art to identify and test anyone of these finite number of sequences without undue experimentation. One would have had a reasonable expectation of success given the routine nature of designing guide nucleic acids in the art and the high skill level of one with ordinary skill in the art.
Response to Applicant’s remarks filed 3 Feb 2026:
Applicant argues that Bull fails to teach or suggest a guide nucleic acid as claimed or corn VSR3, but rather teaches mutations in a barley VRS3. Applicant argues that Accession No. PWZ25266.1 and Gao et al fail to teach a barley VSR3 and fail to teach or provide motivation to use the claimed target regions. Applicant further argues that the combination of cited references provides no teachings or suggestions to modify Bull to provide the claimed guide nucleic acid. Applicant further argues that Examiner is relying on hindsight reasoning and Applicant’s own disclosure to guide the obviousness analysis.
This is not found persuasive.
As a first matter, in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, as set forth above, one would be motivated to substitute the barely of Bull with the gene encoding Accession No. PWZ5256.1 (a homolog of the barley gene taught by Bull) and the methods of Gao et al given that increased grain size is a desirable trait in maize, which like barley is a cereal crop, and given the teachings of Gao et al directed to improving yield in a maize plant by Crispr-Cas9 mediated editing of an endogenous gene. Though the barley gene of Bull et al and Accession No. PWZ5256.1 share less than 80% sequence identity to one another the teachings of the prior art references would have enabled one of skill in the art to identify the two polypeptides as homologs. One would be further motivated to combine the prior art teachings, as also explained above, to target the JmjN domain (as recited in claims 93 and 128 as a target site given the teachings of Bull et al that frameshift mutations in said region in the barely homolog caused loss of function and increased grain size. Regarding claim 126, as explained above, a polypeptide with 100% identity to SEQ ID NO: 71 inherently comprises the recited domains. Finally, given that there are only a finite number of targets in the JmjN domain, it would have been obvious to a person of ordinary skill in the art to identify and test anyone of these finite number of sequences without undue experimentation and arrive at the guide nucleic acid as recited in claim 127.
For these reasons, the rejection is maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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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/ALEKSANDAR RADOSAVLJEVIC/Examiner, Art Unit 1662
/BRENT T PAGE/Primary Examiner, Art Unit 1663
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