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 .
Election/Restrictions
1. Applicant’s election with traverse of Group I (claims 23-24, 28, 30 and 33-35) and SEQ ID NO: 1 (encoded by SEQ ID NO: 2 (genomic sequence) and SEQ ID NO: 3 (cDNA sequence) and mutation corresponding to position 680 in SEQ ID NO: 1 in the reply filed on April 24, 2026 is acknowledged.
Applicant primarily argues, that Wu et al. or Huang et al. do not teach or suggest expressing a POLD1 polypeptide comprising a mutation in or near its active center results in disease resistance in a plant (response, page 9).
Applicant’s arguments are carefully considered but are deemed to be unpersusaive.
It is noted that the technical feature common to Groups I-IV is directed to a polynucleotide encoding a mutant POLD1 polypeptide or to reducing or eliminating expression of a POLD1 polypeptide in a plant. Furthermore, the scope of the recitation “near the active center of the POLD1 polypeptide” is broad and indefinite, as the term “near” lacks defined boundaries and, therefore, reasonably encompasses any location within the polypeptide. The issue presented is whether it would have been obvious to reduce or eliminate expression of the POLD1 polypeptide to obtain plants resistant to geminivirus infection. Wu et al. teach that silencing expression of POLD1 in plants results in reduced or eliminated geminivirus replication upon infection. Huang et al. further teach the production of transgenic plants and seeds exhibiting resistance to geminivirus disease by transforming plants with expression cassettes designed to suppress or eliminate viral replication. In view of these teachings, it would have been obvious to a person of ordinary skill in the art, at the time of the invention, to utilize a known POLD1 sequence, including, for example, the GenBank accession XP_021631270.1 sequence corresponding to SEQ ID NO: 1, as a starting template for mutagenesis. It would have been further obvious to inactivate or silence expression of the POLD1 protein by selectively editing or mutagenizing amino acid residues, including those at or near the active site, using routine and well-known techniques such as CRISPR/Cas9. Such techniques were widely known and routinely practiced prior to the earliest filing date of the claimed invention. Accordingly, modifying or inactivating the endogenous POLD1 gene to reduce or eliminate its expression, thereby conferring resistance to geminivirus, would have been an obvious matter of design choice in view of the combined teachings of Wu et al. and Huang et al.
Claims 1-6, 12, 22-24, 28, 30, 33-35, 40, 53, 61, 72 and 75 are pending. Claims 7-11, 13-21, 25-27, 29, 31, 32, 36-39, 41-52, 54-60, 62-71, 73-74 and 76-84 are cancelled by the Applicant. Claims 1-6, 12, 22, 40, 53, 61, 72 and 75 are directed to non-elected subject matter are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim. SEQ ID NOs: 5-9, 10-13, 14-17, 18-21, 22-25, 26-29, 30-33, 34-37, 38-41, 42-45, 46-49, 50-52, 53, 54, 55, 56, 57, and 58-60, and mutation(s) corresponding to positions 252 to 253, 290, 426 to 431, 452 to 458, 516 to 552, 593 to 604 to 609, 647 to 668, 674 to 679, 681-698, 708 to 719, 748 to 749, 780 to 787, and 818 in SEQ ID NO: 1 are also withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions.
Accordingly, Claims 23-24, 28, 30 and 33-35 and SEQ ID NO: 1 (encoded by SEQ ID NO: 2 (genomic sequence) and SEQ ID NO: 3 (cDNA sequence) and mutation corresponding to position 680 in SEQ ID NO: 1 are examined on merits in this Office action. This restriction is made FINAL.
Applicant is reminded that upon the cancellation of claims to a non-elected invention, the inventorship must be amended in compliance with 37 CFR 1.48(b) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. Any amendment of inventorship must be accompanied by a request under 37 CFR 1.48(b) and by the fee required under 37 CFR 1.17(i).
Information Disclosure Statement
2. Initialed and dated copy of Applicant’s IDS form 1449 filed January 27, 2025 is attached to the instant Office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
3. Claims 24 and 28 are objected to because of the following informalities:
Claim 24 is objected for having non-elected subject matter. The non-elected subject matter is mutation(s) corresponding to positions 252 to 253, 290, 426 to 431, 452 to 458, 516 to 552, 593 to 604 to 609, 647 to 668, 674 to 679, 681-698, 708 to 719, 748 to 749, 780 to 787, and 818 of SEQ ID NO: 1.
Claim 24 is objected for having non-elected subject matter. . The non-elected subject matter is. SEQ ID NOs: 5-9, 10-13, 14-17, 18-21, 22-25, 26-29, 30-33, 34-37, 38-41, 42-45, 46-49, 50-52, 53, 54, 55, 56, 57 and 58-60.
Appropriate action is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
4. Claims 23-24, 28, 30 and 33-35 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Step 1: Statutory Category
Claims 23-24, 28, 30 and 33-35 are directed to a statutory category of invention. Independent claim 23 recites a “method,” which is a process. The dependent claims further limit the method. Accordingly, the claims fall within one of the four statutory categories (process, machine, manufacture, or composition of matter).
Step 2A, Prong One: Judicial Exception
The claims are directed to a judicial exception. Specifically, the claims recite modifying a plant cell to express a mutated POLD1 polypeptide to enhance resistance to a geminivirus. This describes a relationship between a naturally occurring protein (POLD1) and a natural phenomenon (plant resistance to viral infection) due to naturally occurring mutation(s) which makes POLD1 protein inactive or exhibits reduced activity thereby preventing or reducing geminivirus infection resulting in resistance. Even, Applicant’s own specification admits Cassava (Mamhot esculenta Crantz) plant having mutation in POLD1 gene encoding protein and exhibiting resistance to geminivirus (See in particular, example 1, Table 2). Also see for example, Shen et al. (Theoretical Strazand Applied Genetics (2025) 138:22 https://doi.org/10.1007/s00122-024-04803-w; See in particular abstract; Figs. 1-8) who teach naturally occurring mutation in tomato POLD1 protein conferring geminivirus resistance.
Such relationships constitute natural laws or natural phenomena. The claimed mutation “in or near the active center” does not define a specific structural change but instead broadly encompasses alterations to a naturally occurring protein and its natural function. Therefore, the claims are directed to a judicial exception. See Mayo Collaborative Services v. Prometheus Laboratories, Inc. and Association for Molecular Pathology v. Myriad Genetics, Inc..
Step 2A, Prong Two: Integration into a Practical Application
The claims do not integrate the judicial exception into a practical application. The additional elements recited in the claims include steps such as modifying a plant cell, transforming a plant cell, performing genome editing, regenerating a plant, and selecting for resistance.
These steps are recited at a high level of generality and represent well-understood, routine, and conventional activities in the field of plant biotechnology. For example, claims 30 and 33 recite transformation and genome editing using ZFN, TALEN, or CRISPR/Cas systems, which are standard techniques.
The claims do not impose meaningful limits on the judicial exception or apply it in a manner that improves a technological process or provides a particular machine or transformation beyond what is routine. Accordingly, the claims fail to integrate the exception into a practical application.
Step 2B: Inventive Concept
The claims do not include additional elements that amount to significantly more than the judicial exception. The recited steps merely apply the natural relationship using conventional techniques.
The broad functional language, including mutations “in or near the active center” and sequence identity ranges of 80% to 99%, does not provide a specific or inventive implementation. Instead, these limitations encompass a wide range of naturally occurring or routine variations. When considered individually and as an ordered combination, the additional elements do not amount to an inventive concept sufficient to transform the judicial exception into patent-eligible subject matter. See Alice Corp. v. CLS Bank International.
Accordingly, claims 23-24, 28, 30 and 33-35 are directed to a judicial exception and do not recite significantly more than the exception. Therefore, the claims are not patent-eligible under 35 U.S.C. §101. This is not patent-eligible pursuant to the Supreme Court decision in Association for Myriad: Assoc. for Molecular Pathology v. Myriad Genetics, Inc. (2013), Alice Corp.: Alice Corp. Pty. Ltd. v. CLS Bank Int’l (2014), Mayo: Mayo Collaborative Services v. Prometheus Labs. Inc. (2012) and Bilski: Bilski v. Kappos (2010).
the time 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.
5. Claims 23-24, 28, 30 and 33-35 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 pre-AIA the applicant regards as the invention.
Claim 23 is rejected under 35 U.S.C. 112(b), as being indefinite in its recitation “near the active center" because it fails to provide objective boundaries for determining the scope of claim. The term “near” is a term of degree, but the claim and the specification do not provide (i) a defined spatial distance (e.g. number of residues from the active site); (ii) structural boundaries (e.g., specific domains or motifs) or (iii) any standard for measuring proximity to the active center.
Accordingly, one of ordinary skill in the art would not be reasonably certain as to which amino acid positions fall within the scope of “near the active center” and which do not.
Claim 23 is rejected under 35 U.S.C. 112(b), as being indefinite in its recitation “enhancing”, because the term "enhancing" is a relative term which renders the claim indefinite. The term “enhancing" is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The claim lacks comparative basis with a non-transgenic control plant of the same species lacking expression of the POLD 1 polypeptide which comprises a mutation of at least one amino acid in or near the active center of the POLD 1 polypeptide.
Dependent claims are also rejected because they fail to overcome the deficiencies of the parent claims.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
6. Claims 23-24, 28, 30 and 33-35 are rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention.
The Federal Circuit has recently clarified the application of the written description requirement. The court stated that a written description of an invention "requires a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials." University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568; 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). The court also concluded that "naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material." Id. Further, the court held that to adequately describe a claimed genus, Patent Owner must describe a representative number of the species of the claimed genus, and that one of skill in the art should be able to "visualize or recognize the identity of the members of the genus." Id.
Finally, the court held:
A description of a genus of cDNAs may be achieved by means of a recitation of a representative number of cDNAs, defined by nucleotide sequence, falling within the scope of the genus or a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. Id.
See also MPEP Section 2163, page 174 of Chapter 2100 of the August 2005 version, column 1, bottom paragraph, where it is taught that
[T]he claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.
See also Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ 2d 1016 at 1021, (Fed. Cir. 1991) where it is taught that a gene is not reduced to practice until the inventor can define it by "its physical or chemical properties" (e.g. a DNA sequence).
Claims are broadly drawn to a method of enhancing resistance of a plant to infection by a geminivirus, the method comprising: modifying at least one plant cell to comprise a polynucleotide encoding a POLD 1 polypeptide, wherein the POLD 1 polypeptide comprises a mutation of at least one amino acid in or near the active center of the POLD 1 polypeptide, or wherein the POLD1 polypeptide comprises a mutation of at least one amino acid at a position corresponding to position 680 of SEQ ID NO: 1, or wherein the POLD1 polypeptide has at least 80%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1 or wherein the polynucleotide encoding the POLD1 polypeptide has at least 80%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to at least one of the nucleotide sequences set forth in SEQ ID NOs: 2 or 3, or wherein the modifying comprises transforming at least one plant cell with a polynucleotide encoding the POLD 1 polypeptide, or wherein the modifying comprises using genome editing to modify the nucleotide sequence of a native gene in the genome of the plant cell, or wherein the genome editing comprises using a zinc-finger nuclease (ZFN), a TAL (transcription activator-like) effector nuclease (TALEN), or a Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR- associated nuclease (CRISPR/Cas nuclease) system, or wherein the plant cell is regenerated into a plant comprising in its genome the polynucleotide, or wherein the method further comprising selecting for a plant or a plant cell having enhanced resistance to the geminivirus as compared to a corresponding control plant or plant cell without the polynucleotide.
Claim 23 is directed to a polynucleotide encoding any POLD1 polypeptide from any source and having a mutation of at least one amino acid “in or near the active center” of said POLD1 polypeptide, wherein the plant has enhanced resistance to at least one geminivirus.
The breadth of claim encompasses any POLD1 polypeptide from any source and having any mutation or mutations in or around active center and having the function of imparting resistance to geminivirus.
The breadth of dependent claim 24 encompasses any type of mutation or mutations at position 680 of SEQ ID NO: 1, and having the function of imparting resistance to geminivirus.
The breadth of claim 28 encompasses unspecified changes in the amino acid sequence having 80%, to 99% identity to SEQ ID NO: 1 and unspecified nucleotide changes in the POLD1 nucleotide sequence having 80%, to 99% identity to SEQ ID NO: 2 (genomic sequence encoding SEQ ID NO: 1) or SEQ ID NO: 3 (cDNA sequence encoding SEQ ID NO: 1) and having the function of imparting resistance to a geminivirus.
The instant specification, however only describes naturally occurring Cassava (Mamhot esculenta Crantz) plant growing in wild having G680V substitution type of mutation in SEQ ID NO: 1, and exhibiting function of enhanced resistance to a geminivirus. The mutant amino acid SEQ ID NO: 1 sequence having G680V substitution type of mutation is shown in SEQ ID NO: 53 which is encoded by a mutant genomic sequence as set forth in SEQ ID NO: 54 or by a mutant cDNA sequence as set forth in SEQ ID NO: 56. See in particular, Example 1, Table 2 of the specification. While, the specification Only states in a prophetic manner to transfer plants with said mutant sequences using gene editing techniques, such as CRISPR/Cas nuclease, ZFN or TALEN at paragraphs [0135], [0076], [0078] or [0135], however it is noted that the specification lacks experimental guidance to produce a geminivirus resistant plant using said naturally occurring mutant sequence of SEQ ID NO: 1.
The specification does not provide an adequate written description for the structural boundaries of the “active center” of POLD1; what constitutes “near” the active center; and the correlation between any mutation in or near the active center and enhanced resistance to at least one geminivirus across the full scope of plants and geminiviruses encompassed by the claim. The claim encompasses any amino acid substitution in an undefined region of a large, multifunctional DNA polymerase subunit, in any transgenic plant, conferring resistance to any geminivirus. The disclosure does not demonstrate possession of such a broad genus. There is no representative number of species showing that mutations throughout the active center region uniformly confer enhanced geminivirus resistance, nor structural features common to the genus that would allow one skilled in the art to recognize the claimed members.
The specification does not provide sufficient written description support for the full breadth of substitutions encompassed by “at least one amino acid” in or near active center, which encompass 19 possible amino acids at each listed position; the combinatorial breadth of mutations across multiple listed positions; and a demonstrated nexus between each position, and enhanced resistance to at least one geminivirus. The claims encompass a vast number of possible sequence variants. The specification does not disclose a representative number of working examples covering the scope of the recited substitutions nor structural features common to the genus sufficient to show possession. Absent sufficient representative species or identifying characteristics, the written description requirement is not satisfied.
Additionally, claim 24 recite specific amino acid position corresponding position 680 of SEQ ID NO: 1. The specification does not provide sufficient written description support for the full breadth of substitutions encompassed by “at least one amino acid” which encompasses 19 possible amino acids at the position 680 of SEQ ID NO: 1; the combinatorial breadth of mutations across position 680 of SEQ ID NO: 1; and a demonstrated nexus between each recited substitution and enhanced resistance to at least one geminivirus. The claims encompass a vast number of possible sequence variants. The specification does not disclose a representative number of working examples covering the scope of the recited substitutions nor structural features common to the genus sufficient to show possession. Absent sufficient representative species or identifying characteristics, the written description requirement is not satisfied.
The specification fails to provide representative examples demonstrating that mutations across the claimed active center consistently confer enhanced resistance while maintaining plant function.
Furthermore, claim 28 recites POLD1 polypeptides having at least 80%, 90%, 95%, 98%, or 99% sequence identity to SEQ ID NO: 1 encoded by SEQ ID NOs: 2 (genomic) or 3 (cDNA). The disclosure does not demonstrate possession of the full scope of variants encompassed by as low as 80% identity to each listed sequence. An 80% to 99% identity threshold permits extensive sequence variation across a large catalytic protein.
Nucleic acid sequences having 80% sequence identity to the 1091 amino acid long SEQ ID NO: 1 would encode proteins with 218 random amino acid substitutions relative to SEQ ID NO: 1.
Nucleic acid sequences having 90% sequence identity to the 1091 amino acid long SEQ ID NO: 1 would encode proteins with 109 random amino acid substitutions relative to SEQ ID NO: 1.
Nucleic acid sequences having 95% sequence identity to the 1091 amino acid long SEQ ID NO: 1 would encode proteins with 54 random amino acid substitutions relative to SEQ ID NO: 1.
Nucleic acid sequences having 98% sequence identity to the 1091 amino acid long SEQ ID NO: 1 would encode proteins with 21 random amino acid substitutions relative to SEQ ID NO: 1.
Nucleic acid sequences having 99% sequence identity to the 1091 amino acid long SEQ ID NO: 1 would encode proteins with 10 random amino acid substitutions relative to SEQ ID NO: 1.
Nucleic acid sequences with 80% identity to instant SEQ ID NO: 2 would have 4497 substitutions relative to 22487 nucleotides of SEQ ID NO: 2; these encompass polynucleotide sequences that either encode no protein or encode proteins with 1091 amino acid substitutions relative to SEQ ID NO: 1. These proteins would have 0% identity to SEQ ID NO: 1.
Nucleic acid sequences with 90% identity to instant SEQ ID NO: 2 would have 2248 substitutions relative to 22487 nucleotides of SEQ ID NO: 2; these encompass polynucleotide sequences that either encode no protein or encode proteins with 1091 amino acid substitutions relative to SEQ ID NO: 1. These proteins would have 0% identity to SEQ ID NO: 1.
Nucleic acid sequences with 95% identity to instant SEQ ID NO: 2 would have 1124 substitutions relative to 22487 nucleotides of SEQ ID NO: 2; these encompass polynucleotide sequences that either encode no protein or encode proteins with 1091 amino acid substitutions relative to SEQ ID NO: 1. These proteins would have 0% identity to SEQ ID NO: 1.
Nucleic acid sequences with 98% identity to instant SEQ ID NO: 2 would have 449 substitutions relative to 22487 nucleotides of SEQ ID NO: 2; these encompass polynucleotide sequences that either encode no protein or encode proteins with 1091 amino acid substitutions relative to SEQ ID NO: 1. These proteins would have 58% identity to SEQ ID NO: 1.
Nucleic acid sequences with 99% identity to instant SEQ ID NO: 2 would have 224 substitutions relative to 22487 nucleotides of SEQ ID NO: 2; these encompass polynucleotide sequences that either encode no protein or encode proteins with 1091 amino acid substitutions relative to SEQ ID NO: 1. These proteins would have 79% identity to SEQ ID NO: 1.
Nucleic acid sequences with 80% identity to instant SEQ ID NO: 3 would have 812 substitutions relative to 4063 nucleotides of SEQ ID NO: 3; these encompass polynucleotide sequences that encode proteins with 812 amino acid substitutions relative to SEQ ID NO: 1. These proteins would have 25% identity to SEQ ID NO: 1.
Nucleic acid sequences with 90% identity to instant SEQ ID NO: 3 would have 406 substitutions relative to 4063 nucleotides of SEQ ID NO: 3; these encompass polynucleotide sequences that encode proteins with 406 amino acid substitutions relative to SEQ ID NO: 1. These proteins would have 62% identity to SEQ ID NO: 1.
Nucleic acid sequences with 95% identity to instant SEQ ID NO: 3 would have 203 substitutions relative to 4063 nucleotides of SEQ ID NO: 3; these encompass polynucleotide sequences that encode proteins with 203 amino acid substitutions relative to SEQ ID NO: 1. These proteins would have 81% identity to SEQ ID NO: 1.
Nucleic acid sequences with 98% identity to instant SEQ ID NO: 2 would have 81 substitutions relative to 4063 nucleotides of SEQ ID NO: 3; these encompass polynucleotide sequences that encode proteins with 81 amino acid substitutions relative to SEQ ID NO: 1. These proteins would have 92% identity to SEQ ID NO: 1.
Nucleic acid sequences with 99% identity to instant SEQ ID NO: 2 would have 40 substitutions relative to 4063 nucleotides of SEQ ID NO: 3; these encompass polynucleotide sequences that encode proteins with 40 amino acid substitutions relative to SEQ ID NO: 1. These proteins would have 96% identity to SEQ ID NO: 1.
The specification does not describe which residues may vary, what structural constraints are required, or which variants maintain the claimed functional property of enhanced geminivirus resistance. Accordingly, the specification does not reasonably convey possession of the full genus defined by the broad percent identity limitations.
Thus, the breadth of claims encompass a very large genus having species with unknown structures, whose function cannot be reliably predicted.
The state of the art for inferring a structure function relationship based on sequence homology is highly unpredictable. The functional prediction of a protein based on structural comparison is not consistent with an empirical assessment of its function. See for example, Doerks et al., (TIG, 14:248-250, 1998) who teach that sequence homology is not sufficient to determine functionality of an uncharacterized protein. The homologs that scored best in PSI-BLAST analysis failed to share same catalytic activity. The reference clearly emphasizes that computer analysis of genome sequences is flawed, and overpredictions are common because the highest scoring database protein does not necessarily share the same or even similar functions. See in particular, page 248, 1st paragraph; page 248, right column, 2nd paragraph.
Also see Smith et al. (Nature Biotechnology, 15:1222-1223, 1997) who teach that there are numerous cases in which proteins of very different functions are homologous. See in particular, page 1222, last paragraph.
Also see Bork et al. (TIG, 12:425-427, 1996) who teach that homology search methods are stretched and spurious hits are taken as real. The reference further teaches that similarities determined by homology search might only be restricted to certain domains of the uncharacterized protein, whereas the whole protein is required for the functionality of the protein. See page 426, right column, 1st paragraph.
The specification does not describe the structure for representative members of Applicant’s broadly claimed genus comprising variants derived from diverse sources as encompassed by the breadth of claims and thus their function of imparting resistance to geminivirus in a plant is either unknown or unpredictable.
The only species described in the specification is SEQ ID NO: 1 encoded by SEQ ID NOs: 2, or 3 from cassava plant species. Transgenic plants expressing mutant proteins are not described.
One of skill in the art would not recognize that Applicant was in possession of the necessary common attributes or features of the genus in view of the disclosed species. Since the disclosure fails to describe the common attributes that identify members of the genus, and because the genus is highly variant, SEQ ID NOs: 1-3 having G680V substitution type of mutation is insufficient to describe the claimed genus.
Therefore, given the lack of written description in the specification with regard to the structural and functional characteristics of the claimed compositions, it is not clear that Applicant was in possession of the claimed genus at the time this application was filed.
Accordingly, there is lack of adequate description to inform a skilled artisan that applicant was in possession of the claimed invention at the time of filing. See Written Description guidelines published in Federal Register/Vol.66, No. 4/Friday, January 5, 2001/Notices; p. 1099-1111.
Claim Rejections - 35 USC § 103
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
7. Claim(s) 23-24, 28, 30 and 33-35 are rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (Nature communication,12.1 (2021):2780, 10 pages), further in view of Huang et al. (US Patent publication No. 2019/0249189 A1, published), Xie et al. (Molecular Plant, 6:1975-1983, 2013) and (NCBI, GenBank NO. XP_021631270.1, Published 2017, see pages 1-2).
Wu et al. teach that geminiviruses rely exclusively on host DNA replication machinery and specifically identifies plant DNA polymerases α and δ as required host factors for productive viral replication. Wu further demonstrates that DNA polymerase α is required for conversion of the viral single-stranded DNA genome into a double-stranded DNA intermediate, while DNA polymerase δ mediates synthesis and amplification of new viral DNA genomes. Through protein interaction and functional assays, Wu shows that subunits of polymerases α and δ physically associate with the viral replication enhancer protein C3, which selectively recruits polymerase δ to promote efficient viral DNA accumulation. In addition, Wu demonstrates using polymerase-defective mutant backgrounds that plants with strongly reduced or null polymerase δ function exhibit markedly decreased viral DNA accumulation upon infection, consistent with an inability of the virus to replicate efficiently in the absence of functional polymerase δ, although such mutants are used as experimental systems and are associated with impaired host DNA replication. Importantly, Wu et al., further shows that reduction of polymerase δ function results in decreased viral DNA accumulation and impaired replication, whereas the presence of functional polymerase δ supports productive infection, thereby establishing polymerase δ as a required host susceptibility factor for geminivirus replication. See in particular, Abstract; Materials and Methods; Results; Discussion; and Figures 1–4.
Wu et al. do not expressly disclose modifying through mutation plant POLD1 to confer resistance to geminivirus infection. Wu et al. also do not teach modifying instant SEQ ID NO: 1.
Huang et al. teach methods of transforming crop plants, including soybean, maize, and tomato, with expression cassettes designed to suppress or eliminate geminivirus replication. Huang et al. further teach producing transgenic plants and seeds exhibiting resistance to geminivirus disease. See, e.g., paragraphs [0045], [0052], [0054], [0109]–[0113], [0151], [0156], [0159], [0162], [0163], [0175], [0176]; Figs. 13B, 14A; Examples 4 and 7; Tables 4 and 8.
Xi et al. teach using RNA-guided genome editing using CRISPR/Cas based system in targeting an endogenous plant gene to suppress or eliminate its expression in plant cells. The reference clearly suggests the advantages and precision of using CRISPR/Cas based system of targeting endogenous plant genes from diverse plant species to eliminate or suppress expression of said targeted endogenous gene. Xi et al. further teach that CRISPR-cas system can be used as an efficient and powerful tool for gene editing and precise genome editing in plants by using multiple guided RNAs (gRNAs) with a 20-22 nt region designed to pair with distinct genomic sites which are followed by the protospacer-adjacent motif (PAM). Xi et al. clearly suggest that using multiple guided RNAs (gRNAs) to achieve multiple edits within the targeted endogenous gene of the plant cell. See in particular, abstract; Figures 1-5; results and discussion, methods, pages 1975-1981; also see supplementary data at the end of the reference.
GenBank accession XP_021631270.1 discloses a nucleotide sequence encoding a DNA polymerase delta catalytic subunit isoform X1 having 100% identity to Applicant’s SEQ ID NO: 1. The sequence homology results are as follows:
Query Match 100.0%; Score 5658; DB 1; Length 1091;
Best Local Similarity 100.0%;
Matches 1091; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MNRNGNTRKRPPPTSQPTPSPPAPKHQATTPAVDDEFVDEDVFLDETLIAEEENLILRDL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MNRNGNTRKRPPPTSQPTPSPPAPKHQATTPAVDDEFVDEDVFLDETLIAEEENLILRDL 60
Qy 61 EERQALASRLAKWSRPSLSHEYTSQSRSIIFQQLEIDYVIGESHKELLPDRSGVAAIIRI 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 EERQALASRLAKWSRPSLSHEYTSQSRSIIFQQLEIDYVIGESHKELLPDRSGVAAIIRI 120
Qy 121 FGVTREGHSVCCLVHGFEPYFYISCPPGMGPDDISRFQQILEGRMKEMNRNSQVPKFVRR 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 FGVTREGHSVCCLVHGFEPYFYISCPPGMGPDDISRFQQILEGRMKEMNRNSQVPKFVRR 180
Qy 181 IEMVQKRSIMYYQQQPSHPFLKIVVALPTMVASCRGILDKGIHIDGLGMKSFMTYESNVL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 IEMVQKRSIMYYQQQPSHPFLKIVVALPTMVASCRGILDKGIHIDGLGMKSFMTYESNVL 240
Qy 241 FALRFMIDCNVVGGNWIEVPAGKYKKTSKNLSYGQLEFDCLYSELISHAPEGEFSKMAPF 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 FALRFMIDCNVVGGNWIEVPAGKYKKTSKNLSYGQLEFDCLYSELISHAPEGEFSKMAPF 300
Qy 301 RILSFDIECAGRKGHFPEPTHDPVIQVANLVTMQGEDQPFIRNVMTLNSCSPIVGVDVMS 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 RILSFDIECAGRKGHFPEPTHDPVIQVANLVTMQGEDQPFIRNVMTLNSCSPIVGVDVMS 360
Qy 361 FDTEREVLLAWRDFIREVDPDIIIGYNICKFDLPYLIERAETLGIAEFPVFGRVKNSRVR 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 FDTEREVLLAWRDFIREVDPDIIIGYNICKFDLPYLIERAETLGIAEFPVFGRVKNSRVR 420
Qy 421 VKDTTFSSRQYGTRESKEVTLEGRVQFDLLQAMQRDYKLSSYSLNSVSAHFLSEQKEDVH 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 VKDTTFSSRQYGTRESKEVTLEGRVQFDLLQAMQRDYKLSSYSLNSVSAHFLSEQKEDVH 480
Qy 481 HSIISDLQNGNAETRRRLAVYCLKDAYLPQRLLDKLMFIYNYVEMARVTGVPLSFLLSRG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 HSIISDLQNGNAETRRRLAVYCLKDAYLPQRLLDKLMFIYNYVEMARVTGVPLSFLLSRG 540
Qy 541 QSIKVLSQLLRKAKQKNLVIPNVKQAGSEQGTYEGATVLEARAGFYEKPIATLDFASLYP 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 QSIKVLSQLLRKAKQKNLVIPNVKQAGSEQGTYEGATVLEARAGFYEKPIATLDFASLYP 600
Qy 601 SIMMAYNLCYCTLVTPEDVRKLNIPPECVNKTPSGETFVKSNLQKGILPEILEELLAARR 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 SIMMAYNLCYCTLVTPEDVRKLNIPPECVNKTPSGETFVKSNLQKGILPEILEELLAARR 660
Qy 661 RAKADLKEAKDPLVKAVLDGRQLALKVSANSVYGFTGATIGQLPCIEISSSVTSYGRQMI 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 RAKADLKEAKDPLVKAVLDGRQLALKVSANSVYGFTGATIGQLPCIEISSSVTSYGRQMI 720
Qy 721 EHTKKLVEEKFTITGGYEHNAEVIYGDTDSVMVQFGVPTVEEAMKLGREAAECISGTFIK 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 EHTKKLVEEKFTITGGYEHNAEVIYGDTDSVMVQFGVPTVEEAMKLGREAAECISGTFIK 780
Qy 781 PIKLEFEKVYYPYLLISKKRYAGLFWTNPNKFDKMDTKGIETVRRDNCLLVKNLVNECLH 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 PIKLEFEKVYYPYLLISKKRYAGLFWTNPNKFDKMDTKGIETVRRDNCLLVKNLVNECLH 840
Qy 841 KILIDRDVPGAVQYVKNTISDLLMNRMDLSLLVITKGLTKTGDDYEVKAAHVELAERMRK 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 KILIDRDVPGAVQYVKNTISDLLMNRMDLSLLVITKGLTKTGDDYEVKAAHVELAERMRK 900
Qy 901 RDAATAPNVGDRVPYVIIKAAKGAKAYERSEDPIYVLENNIPIDPQYYLENQISKPLLRI 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 RDAATAPNVGDRVPYVIIKAAKGAKAYERSEDPIYVLENNIPIDPQYYLENQISKPLLRI 960
Qy 961 FEPILKNASKELLHGSHTRSISISTPSNSGIMKFAKKQLSCIGCKALISNSDRTLCTHCK 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 FEPILKNASKELLHGSHTRSISISTPSNSGIMKFAKKQLSCIGCKALISNSDRTLCTHCK 1020
Qy 1021 GREAELYCKTVSQVSELELLFGRLWTQCQECQGSLHQDVLCTSRDCPIFYRRKKAQKDMA 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 GREAELYCKTVSQVSELELLFGRLWTQCQECQGSLHQDVLCTSRDCPIFYRRKKAQKDMA 1080
Qy 1081 EAKRQLDRWNF 1091
|||||||||||
Db 1081 EAKRQLDRWNF 1091
Given (i) Wu et al. teach that reduction of POLD1 function results in decreased viral DNA accumulation and impaired replication, whereas the presence of functional POLD1 supports productive infection; (ii) Huang et al. teach methods of transforming crop plants, with expression cassettes designed to suppress or eliminate geminivirus replication; and (iii) Xi et al. teach using RNA-guided genome editing using CRISPR/Cas nuclease based system in targeting an endogenous plant gene to suppress or eliminate its expression in plant cells, it would have been obvious to one of ordinary skill prior to earliest filing of the claimed invention to down regulate expression of any plant endogenous POLD1 gene encoding protein using any technique, including commonly known and well tested CRISPR/Cas nuclease method of gene editing as taught by Xi et al., by specifically targeting/modifying any essential amino acid(s) within active center, including the one that corresponds to residue 680 as a matter of design choice using known plant transformation techniques, including the one taught by Huang et al., for the purpose of generating geminivirus-resistant transgenic crops and seeds derived therefrom. It may be noted that expanding a demonstrated resistance strategy from a model plant (tobacco) to agriculturally relevant species constitutes routine optimization and predictable use of prior art elements according to their established functions.
Further, it would have been obvious to utilize any known POLD1 sequence, including the XP_021631270.1 sequence corresponding to SEQ ID NO: 1, as the starting template for mutagenesis using Xi et al., CRISPR/Cas nuclease based technique. It may be noted that selection of a particular homologous POLD1 sequence for mutagenesis represents routine design choice, as the prior art establishes both the structure–function relationship of the active site and the predictable outcome of introducing mutations therein. No unexpected results are apparent from selecting the specific sequence corresponding to SEQ ID NO: 1.
Accordingly, the claimed invention represents the predictable combination of prior art elements with a reasonable expectation of success.
8. Claims 23-24, 28, 30 and 33-35 are rejected under 35 U.S.C. § 103 as being unpatentable over Nagar et al. (The Plant Cell, 7(6):705-719, 1995) and Strzalka et al. (Annals of Botany, 107(7):1127-1140, 2011), and further in view of Huang et al. (US Patent publication No. 2019/0249189 A1, published), Xie et al. (Molecular Plant, 6:1975-1983, 2013) and (NCBI, GenBank NO. XP_021631270.1, Published 2017, see pages 1-2).
Nagar et al. teach that geminivirus infection induces accumulation of host DNA replication proteins in differentiated plant cells and that geminiviruses rely on host DNA replication machinery because they do not encode their own DNA polymerase. The reference demonstrates induction of proliferating cell nuclear antigen (PCNA), a DNA synthesis factor required for replication. See Abstract; pp. 706-707; 713-716; Figs. 1-7. These teachings establish that geminivirus replication depends upon host DNA replication components.
Strzalka et al. teach that PCNA functions as the sliding clamp for DNA polymerase δ and that polymerase δ is a core replicative polymerase whose catalytic activity depends upon conserved active-site domains. The reference further explains that disruption of polymerase structure or its interaction with PCNA impairs DNA synthesis. Thus, polymerase δ catalytic activity is structurally conserved and functionally essential for DNA replication. See Abstract; pp. 1128-1130; 1131–1133; 1132–1134; Figs. 1–8.
Neither Nagar et al. nor Strzalka et al. expressly disclose transforming plants with a polynucleotide encoding mutant SEQ ID NO: 1.
Huang et al. a teach a method of transforming a plant (e.g. soybean, maize or tomato) with cells an expression cassette comprising sequences directed to target genes to suppress or eliminate geminivirus replication upon infection in a plant. Huang et al. also teach obtaining transgenic plants and transgenic seeds exhibiting resistance to geminivirus disease. See in particular, paragraphs [0109]-[0113]; Figs. 14A, 13B, paragraphs [0045]. [0052], [0054], [0151], [0156], [0159], [0162], [0163], [0175], [0176]; Examples 4 and 7; Tables 4 and 8.
Xi et al. teach using RNA-guided genome editing using CRISPR/Cas based system in targeting an endogenous plant gene to suppress or eliminate its expression in plant cells. The reference clearly suggests the advantages and precision of using CRISPR/Cas based system of targeting endogenous plant genes from diverse plant species to eliminate or suppress expression of said targeted endogenous gene. Xi et al. further teach that CRISPR-cas system can be used as an efficient and powerful tool for gene editing and precise genome editing in plants by using multiple guided RNAs (gRNAs) with a 20-22 nt region designed to pair with distinct genomic sites which are followed by the protospacer-adjacent motif (PAM). Xi et al. clearly suggest that using multiple guided RNAs (gRNAs) to achieve multiple edits within the targeted endogenous gene of the plant cell. See in particular, abstract; Figures 1-5; results and discussion, methods, pages 1975-1981; also see supplementary data at the end of the reference.
NCBI teach a nucleotide sequence encoding DNA polymerase delta catalytic subunit isoform X1 having 100% identity to instant SEQ ID NO: 1. The sequence homology results are as follows:
Query Match 100.0%; Score 5658; DB 1; Length 1091;
Best Local Similarity 100.0%;
Matches 1091; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MNRNGNTRKRPPPTSQPTPSPPAPKHQATTPAVDDEFVDEDVFLDETLIAEEENLILRDL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MNRNGNTRKRPPPTSQPTPSPPAPKHQATTPAVDDEFVDEDVFLDETLIAEEENLILRDL 60
Qy 61 EERQALASRLAKWSRPSLSHEYTSQSRSIIFQQLEIDYVIGESHKELLPDRSGVAAIIRI 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 EERQALASRLAKWSRPSLSHEYTSQSRSIIFQQLEIDYVIGESHKELLPDRSGVAAIIRI 120
Qy 121 FGVTREGHSVCCLVHGFEPYFYISCPPGMGPDDISRFQQILEGRMKEMNRNSQVPKFVRR 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 FGVTREGHSVCCLVHGFEPYFYISCPPGMGPDDISRFQQILEGRMKEMNRNSQVPKFVRR 180
Qy 181 IEMVQKRSIMYYQQQPSHPFLKIVVALPTMVASCRGILDKGIHIDGLGMKSFMTYESNVL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 IEMVQKRSIMYYQQQPSHPFLKIVVALPTMVASCRGILDKGIHIDGLGMKSFMTYESNVL 240
Qy 241 FALRFMIDCNVVGGNWIEVPAGKYKKTSKNLSYGQLEFDCLYSELISHAPEGEFSKMAPF 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 FALRFMIDCNVVGGNWIEVPAGKYKKTSKNLSYGQLEFDCLYSELISHAPEGEFSKMAPF 300
Qy 301 RILSFDIECAGRKGHFPEPTHDPVIQVANLVTMQGEDQPFIRNVMTLNSCSPIVGVDVMS 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 RILSFDIECAGRKGHFPEPTHDPVIQVANLVTMQGEDQPFIRNVMTLNSCSPIVGVDVMS 360
Qy 361 FDTEREVLLAWRDFIREVDPDIIIGYNICKFDLPYLIERAETLGIAEFPVFGRVKNSRVR 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 FDTEREVLLAWRDFIREVDPDIIIGYNICKFDLPYLIERAETLGIAEFPVFGRVKNSRVR 420
Qy 421 VKDTTFSSRQYGTRESKEVTLEGRVQFDLLQAMQRDYKLSSYSLNSVSAHFLSEQKEDVH 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 VKDTTFSSRQYGTRESKEVTLEGRVQFDLLQAMQRDYKLSSYSLNSVSAHFLSEQKEDVH 480
Qy 481 HSIISDLQNGNAETRRRLAVYCLKDAYLPQRLLDKLMFIYNYVEMARVTGVPLSFLLSRG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 HSIISDLQNGNAETRRRLAVYCLKDAYLPQRLLDKLMFIYNYVEMARVTGVPLSFLLSRG 540
Qy 541 QSIKVLSQLLRKAKQKNLVIPNVKQAGSEQGTYEGATVLEARAGFYEKPIATLDFASLYP 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 QSIKVLSQLLRKAKQKNLVIPNVKQAGSEQGTYEGATVLEARAGFYEKPIATLDFASLYP 600
Qy 601 SIMMAYNLCYCTLVTPEDVRKLNIPPECVNKTPSGETFVKSNLQKGILPEILEELLAARR 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 SIMMAYNLCYCTLVTPEDVRKLNIPPECVNKTPSGETFVKSNLQKGILPEILEELLAARR 660
Qy 661 RAKADLKEAKDPLVKAVLDGRQLALKVSANSVYGFTGATIGQLPCIEISSSVTSYGRQMI 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 RAKADLKEAKDPLVKAVLDGRQLALKVSANSVYGFTGATIGQLPCIEISSSVTSYGRQMI 720
Qy 721 EHTKKLVEEKFTITGGYEHNAEVIYGDTDSVMVQFGVPTVEEAMKLGREAAECISGTFIK 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 EHTKKLVEEKFTITGGYEHNAEVIYGDTDSVMVQFGVPTVEEAMKLGREAAECISGTFIK 780
Qy 781 PIKLEFEKVYYPYLLISKKRYAGLFWTNPNKFDKMDTKGIETVRRDNCLLVKNLVNECLH 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 PIKLEFEKVYYPYLLISKKRYAGLFWTNPNKFDKMDTKGIETVRRDNCLLVKNLVNECLH 840
Qy 841 KILIDRDVPGAVQYVKNTISDLLMNRMDLSLLVITKGLTKTGDDYEVKAAHVELAERMRK 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 KILIDRDVPGAVQYVKNTISDLLMNRMDLSLLVITKGLTKTGDDYEVKAAHVELAERMRK 900
Qy 901 RDAATAPNVGDRVPYVIIKAAKGAKAYERSEDPIYVLENNIPIDPQYYLENQISKPLLRI 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 RDAATAPNVGDRVPYVIIKAAKGAKAYERSEDPIYVLENNIPIDPQYYLENQISKPLLRI 960
Qy 961 FEPILKNASKELLHGSHTRSISISTPSNSGIMKFAKKQLSCIGCKALISNSDRTLCTHCK 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 FEPILKNASKELLHGSHTRSISISTPSNSGIMKFAKKQLSCIGCKALISNSDRTLCTHCK 1020
Qy 1021 GREAELYCKTVSQVSELELLFGRLWTQCQECQGSLHQDVLCTSRDCPIFYRRKKAQKDMA 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 GREAELYCKTVSQVSELELLFGRLWTQCQECQGSLHQDVLCTSRDCPIFYRRKKAQKDMA 1080
Qy 1081 EAKRQLDRWNF 1091
|||||||||||
Db 1081 EAKRQLDRWNF 1091
Given Nagar et al.’s teaching that geminiviruses depend on host DNA replication machinery, and Strzalka et al.’s identification of polymerase δ as a central catalytic component whose activity resides in its conserved active center, one of ordinary skill in the art would have been motivated to modify polymerase δ to interfere with viral replication. Because viral genome amplification requires host DNA synthesis activity, altering residues in or near the catalytic center of polymerase δ would have predictably modified enzymatic activity and thereby affected viral replication.
The motivation to combine arises from the recognized strategy of targeting host factors essential to pathogen replication to confer resistance. Under KSR Int’l Co. v. Teleflex Inc., when a known problem exists (geminivirus dependence on host replication machinery) and the art identifies a finite number of predictable solutions (modification of catalytic domains governing polymerase activity), pursuing such solutions constitutes obviousness. Targeted mutagenesis of catalytic residues was a routine molecular biology technique at the time of the invention.
Huang et al. provide established plant transformation methods for introducing nucleic acid constructs into crop plants to obtain geminivirus-resistant transgenic plants and seeds. GenBank accession XP_021631270.1 provides a nucleotide sequence identical to SEQ ID NO: 1, representing a suitable template for mutagenesis.
Accordingly, it would have been obvious to genetically engineer plants by introducing a mutagenized POLD1 nucleic acid sequence containing at least one mutation in or near the active site, using known gene editing techniques including CRISPR/Cas nuclease taught by Xi et al., combined with any plant transformation techniques including the one taught by Huang et al., to obtain transgenic plants expressing a modified POLD1 protein with altered DNA replication activity, thereby impairing geminivirus replication and conferring resistance.
It would have been obvious to utilize any known POLD1 sequence, including the XP_021631270.1 sequence corresponding to SEQ ID NO: 1, as the starting template for mutagenesis using Xi et al., CRISPR/Cas nuclease based technique. It may be noted that selection of a particular homologous POLD1 sequence for mutagenesis represents routine design choice, as the prior art establishes both the structure–function relationship of the active site and the predictable outcome of introducing mutations therein. No unexpected results are apparent from selecting the specific sequence corresponding to SEQ ID NO: 1. Selection of the specific XP_021631270.1 sequence for mutagenesis constitutes routine design choice among homologous POLD1 sequences, with a reasonable expectation of success and no evidence of unexpected results.
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 .
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the "right to exclude" granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
9. Claims 23 and 24 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 61 and 62 of copending Application No. 19/578,566 (‘566 thereafter). This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Instant method claims 23 and 24 recite the same method and claim limitations as copending ‘566 claims 61 and 62, respectively. It may be noted that instant claim 1 has 100% amino acid sequence identity to copending ‘655 SEQ ID NO: 1.
This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
10. Claims 28, 30, 33, 34 and 35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 63-69 of copending Application No. 19/578,566 (‘566 thereafter). .
Although claims 28, 30, 33, 34 and 35 at issue are not identical but they are not patentably distinct from each other from copending ‘566 claims 63-69. For example, claim 63 of copending ‘566 encompasses mutation at position 680 in its SEQ ID NO: 1 which has 100% amino acid sequence identity to instant SEQ ID NO: 1. Likewise claim 64 of copending ‘566 encompasses any mutation other than glycine at position 680 of its SEQ ID NO: 1 which has 100% amino acid sequence identity to instant SEQ ID NO: 1, and thus a species anticipating a genus. Furthermore, claim 65 of copending ‘566 encompasses a valine or an arginine mutation at position 680 of its SEQ ID NO: 1 which has 100% amino acid sequence identity to instant SEQ ID NO: 1, and thus a species anticipating a genus.
The subject matter of copending ‘655 claim 68 is basically a species directed to plant parts with a geminivirus resistance which anticipates the genus of instant claim 23. The copending ‘655 claim 66 is directed to at least 80% to 99% identity to SEQ ID NO: 1, which is encompassed by instant claim 28. Likewise, the copending ‘655 claim 67 is directed to at least 80% to 99% identity to SEQ ID NOs: 2-3, which is encompassed by instant claim 28.
Likewise, it would have been obvious to cross, genotype and select mutant plants having a mutation in POLD1 gene to obtain geminivirus resistant crop plants of copending claim 69 by adding these method steps to instant method claims. Genotyping and selection is a routinely used tools in obtaining transgenic plants with desired traits as discussed thoroughly in the entire instant and copending ‘655 specification, and thus rendering copending claim 69 obvious.
It would have been obvious to use genome editing techniques (routinely used as described in instant and copending specification) to insert desired mutations as recited in instant claim 33, to practice the claimed method of copending ‘655, and thus rendering instant and copending ‘655 claims obvious.
This is provisional nonstatutory double patenting rejections because the patentably indistinct claims have not in fact been patented.
Conclusion
11. Claims 23-24, 28, 30 and 33-35 are rejected.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Vinod Kumar whose telephone number is (571) 272-4445. The examiner can normally be reached on 8.30 a.m. to 5.00 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amjad A. Abraham can be reached on (571) 270-7058 The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA).
/VINOD KUMAR/Primary Examiner, Art Unit 1663
, to include wherein the plant is within a mixed population of plants comprising other
Prosecution Insights