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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03/21/2025 has been entered.
Election/Restrictions
The amendments received on 04/23/2025 have been entered. Applicant’s amendment to claim 1 has necessitated the reanalysis of the claim resulting in new rejections, see below.
Claims 6-10 and 16 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made with traverse in the reply filed on 04/25/2022 and 10/10/2022.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Claims 1, 6-10, and 16 are pending. Claim 1 is examined in this Office Action.
Rejection that are withdrawn
35 USC § 101 - Lack of Patentable Utility rejection is withdrawn in light of applicant’s amendment of claim 1 by reciting the mutated eIF(iso)4e protein is in a plant cell.
Claim Rejections - 35 USC § 112 - Indefiniteness
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.
Claim 1 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 1, line 1 recite any of a “synthetic eukaryotic cell” wherein in last line it recites “protein is in a plant cell” which renders claim indefinite since it is not clear whether applicant is claiming the protein is in any eukaryotic cell or it is in a plant cell. Because applicant is claiming narrow and broad limitations in same claim, it has created ambiguity about which limitation is required therefore metes and bound of the claim cannot be determined.
Applicant are advised to include the broad claim in an independent claim and the narrower version in a separate, dependent claim.
Claim 1, is indefinite in the recitation of “non-functional”. There are various functions of eIF(iso)4E in plants known in the art. See for example, Salazar-Díaz et al., 2021, Arabidopsis thaliana eIF4E1 and eIF (iso)4E Participate in Cold Response and Promote Translation of Some Stress-Related mRNAs. Frontiers in plant science, 12. Salazar-Díaz teaches a role of eIF(iso)4e in cold acclimation and freezing tolerance by regulating the expression of stress-related genes using knockout mutants of AteIF4E1 or AteIF(iso)4E. (page 1, abstract). Furthermore, Martínez-Silva et al., 2012, Translation initiation factor AteIF(iso)4E is involved in selective mRNA translation in Arabidopsis thaliana seedlings. PloS one, 7(2), e31606, teaches presence of isoforms eIF4E and eIF(iso)4E, is required in a particular proportion for normal plant growth, as well as in the phosphate limitation stress using a knockout (KO) insertion mutant, AtelF(iso)4E-1 (page 2, right paragraph 2). Furthermore, the knockout of eIF(iso)4E in A. thaliana plant conferred resistance to infection by several potyviruses (page 2, right paragraph 4). Thus, it is not clear which of these known functions have to be missing to be considered “non-functional”. Therefore, the metes and bound of non-functional cannot be determined.
Claim 1 recite “the mutated eIF(iso)4e sequence additionally comprises G2046A and G105E substitutions relative to SEQ ID NO:20” renders claim indefinite since it is recited that the substitutions is relative to SEQ ID NO:20, the “relative to” would mean “with regard to : in connection with” (Merriam Webster dictionary, accessed at https://www.merriam-webster.com/dictionary/relative%20to, on 10/31/2025) and it does not specifically teach the mutation is in SEQ ID NO:20 therefore in connection would also mean specific sequence fragments or patterns in the sequence. Furthermore, since applicant recite “additionally comprises G2046A and G105E substitutions”, therefore it is not clear whether applicant is claiming one substitution or two substitutions in the any of the recited mutant relative to SEQ ID NO: 20.
Applicant are advised to claim the mutation is in SEQ ID NO:20 and the mutation in position G2046A encodes G105E substitutions.
Claim Rejections - 35 USC § 112 - - Inadequate Written Description
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.
Claim 1 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), 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 or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 is broadly drawn to any synthetic eukaryotic cell comprising a mutated eIF(iso)4e protein; wherein the mutated eIF(iso)4e protein is encoded by a mutated eIF(iso)4e sequence with at least 70% identity of SEO ID NO: 20; wherein the mutated eIF(iso)4e sequence additionally comprises a G2046A substitution relative to SEO ID NO:20; and, wherein the mutated eIF(iso)4e sequence additionally comprises a Gl05E mutation relative to SEO ID NO:20, wherein the mutated protein is in a plant cell.
Breadth of the Claim
A mutated eIF(iso)4e sequence with at least 70% identity of SEQ ID NO: 20 would encompass large variants of eIF(iso)4e sequence.
What is Described in the Specification
Applicant describes the following:
Applicant describes the mutation obtained using TILLING method in eIF(iso)4e where the sorting intolerant from tolerant (SIFT) analysis shows result of “Not Tolerated” and SIFT score of “0” (page 21, Table 2, No. 17) for M2(0.3)-552 which is mutant line that comprise nucleotide sequence as of SEQ ID NO: 21 that encodes SEQ ID NO: 25 (page 6);
Applicant describes the mutation obtained using TILLING method in eIF(iso)4e where the SIFT analysis shows result of “Not Tolerated” and SIFT score of “0” (page 21, Table 2, No. 2) for mutant line M2(0.4)-882.
Applicant describes an example of phenotypic analysis of the M2(0.4)-882 mutant by artificial inoculation (page 22 and 23) where the results showed that the M2(0.4)-882 is a eIF4e(iso) missense mutant with amino acid changes Y at position 70 to C (Y70C). Wherein the Table 4 shows mutant line M2(0.4)-882 has severity score of 4 as Severe mottling+ shoe-stinging and/or stunting which is same as WILD TYPE (Table 3 and 4).
Difference Between What was Reduced to Practice and What is Claimed
Applicant has described any mutated eIF(iso)4e sequence with at least 70% identity of SEQ ID NO: 20 other than SEQ ID NO: 21 that has a G2046A substitution, encoding a G105E mutation.
Applicant has not described any of the mutated eIF(iso)4e sequence that comprises a G105E mutation other than SEQ ID NO: 25.
Applicant has not described any mutation in eIF4e(iso) gene other than SEQ ID NO:20 from wild type papaya (gblABIM01010894. ll:25000-29500, Carica papaya chromosome LG6 contig_l0909, whole genome shotgun sequence).
Applicant has not described any use of a mutation of eIF(iso)4e gene that has a G2046A substitution, encoding a G105E mutation in the eIF(iso)4e protein, other than with SIFT score wherein with same score in the existing disclosed example would not have any use and would have same function as wildtype.
Applicant has not described any effect of the G2046A substitution, encoding a G105E mutation in the recited mutated eIF(iso)4e gene with at least 70% identity of SEQ ID NO: 20 in any eukaryotic cell.
Applicant has not describe which function of the eIF(iso)4e protein get lost upon substitution mutation for example whether it is virus susceptibility or other biotic or abiotic stress susceptibility?
Analysis
The purpose of the written description is to ensure that the inventor had possession at the time the invention was made, of the specific subject claimed. For a broad generic claim, the specification must provide adequate written description to identify the genus of the claim.
Applicant has described any mutated eIF(iso)4e sequence with at least 70% identity of SEQ ID NO: 20 other than SEQ ID NO: 21 that has a G2046A substitution, encoding a G105E mutation. The SEQ ID NO:20 is 5001 nucleotides long wherein a variant of SEQ ID NO:20 having at least 80% identity would have 1000 nucleic acid (NA) changes (i.e., substitutions, deletions, insertions, or additions) relative to SEQ ID NO: 20, and this encompasses a genus of nucleic acid sequence that includes at least ~41000 different molecules. For this reason, the genus of nucleic acid molecules having at least 70% identity to SEQ ID NO: 20 is a very large genus of molecules. Joshi et al., 2005, Phylogenetic analysis of eIF4E-family members. BMC evolutionary biology, 5(1), 1-20; teaches within Bootstrap values greater than 70% there are large numbers of sequences of EIF(iso)4E in different eukaryotic species with various taxonomic divisions (Joshi et al. page 9, Figure 4) Wherein applicant has not described any sequence other than a eIF(iso)4e sequence as SEQ ID NO:20 gblABIM01010894. ll:25000-29500, from Carica papaya chromosome LG6 contig_l0909 that has a G2046A substitution, encoding a G105E mutation.
Furthermore, a conserved reason has been described in the eIF(iso)4E across different species of plants, insects, and yeast, wherein the absence by deletion of the region would cause different function of the sequence in eukaryotic organism for example in S. cerevisiae (Joshi, page 3, left last paragraph and right first paragraph). For this reason the evidence shows that any of the mutated eIF(iso)4e sequence with at least 70% identity of SEQ ID NO: 20 would have various functions. Applicant has not described any region that would be conserved in the recited eIF(iso)4e sequence with at least 70% identity of SEQ ID NO: 20 that would have the disclosed function described in specification for any of its use.
Applicant describes SEQ ID NO: 25 pertains to mutated eIF(iso)4e amino acid sequence in papaya (papaya line number M2(0.3)-552), wherein SEQ ID NO: 21 pertains to e1F(iso)4e mutant nucleotide sequence in papaya (papaya mutant line number, M2(0.3)-552 G2046A (GGG->GAG) Gl05E) (Spec, page 6). Applicant has not described structure of any sequence that has G105E mutation other than SEQ ID NO: 25.
Applicant has not described any mutation in eIF4e(iso) gene other than SEQ ID NO:20 from wild type papaya (gblABIM01010894. ll:25000-29500, Carica papaya chromosome LG6 contig_l0909, whole genome shotgun sequence).
Applicant has described an example of phenotypic analysis of the M2(0.4)-882 mutant by artificial inoculation (page 22 and 23) where the results showed that the M2(0.4)-882 is a eIF4e(iso) neutral mutant with amino acid changes Y at position 70 to C (Y70C). The table 4 demonstrates observations , Where the Table 4 shows mutant line M2(0.4)-882 has severity score of 4 as Severe mottling+ shoe-stinging and/or stunting which is same as WILD TYPE (Table 3 and 4).
Hence a mutation of eIF(iso)4e gene that has a G2046A substitution, encoding a G105E mutation in the eIF(iso)4e protein, may not have any disease resistance as M2(0.4)-882 mutant with same SIFT score and analysis and will have same disease severity as WILD TYPE.
Applicant does not describe any function of eIF(iso)4e gene that has a G2046A substitution, encoding a G105E mutation in the eIF(iso)4e protein other than SIFT analysis. SIFT analysis does not provide any credible function for example mutant line M2(0.4)-882 with same SIFT analysis showing result of “Not Tolerated” and SIFT score of “0” as M2(0.3)-552 which is mutant line that comprise nucleotide sequence as of SEQ ID NO: 21 that encodes SEQ ID NO: 25 (page 6),is virus susceptible (see table 4 above).
Flanagan et al., 2010, Using SIFT and PolyPhen to predict loss-of-function and gain-of-function mutations. Genetic testing and molecular biomarkers, 14(4), 533-537, teaches the predictive value of SIFT and concludes that SIFT may be useful in prioritizing changes that are likely to cause a loss of protein function, their low specificity means that their predictions should be interpreted with caution and further evidence to support/refute pathogenicity should be sought before reporting novel missense changes (Flanagan, page 533, Abstract). Furthermore, Miosge et al., 2015, Comparison of predicted and actual consequences of missense mutations. Proceedings of the National Academy of Sciences, 112(37), E5189-E5198, teaches comparison of predicted and actual consequences of missense mutations by SIFT and finds the missense mutation inferred as damaging were only predicted 20% of the time to be accurate (Miosge, page E5192, left paragraph 1, page E5191, Table 1) and suggests requirement of direct experimental measurement of the consequences and phenotyping to interpret missense variation (Miosge, page E5197, left paragraph 1). Thus a function of a gene or mutation is very unlikely to be predicted accurately by SIFT analysis.
Applicant fails to describe which function of the eIF(iso)4e protein get lost upon substitution mutation. There are various functions of eIF(iso)4E in plants known in the art. See for example, Salazar-Díaz et al., 2021, Arabidopsis thaliana eIF4E1 and eIF (iso)4E Participate in Cold Response and Promote Translation of Some Stress-Related mRNAs. Frontiers in plant science, 12. Salazar-Díaz teaches a role of eIF(iso)4e in cold acclimation and freezing tolerance by regulating the expression of stress-related genes using knockout mutants of AteIF4E1 or AteIF(iso)4E. (page 1, abstract). Furthermore, Martínez-Silva et al., 2012, Translation initiation factor AteIF(iso)4E is involved in selective mRNA translation in Arabidopsis thaliana seedlings. PloS one, 7(2), e31606, teaches presence of isoforms eIF4E and eIF(iso)4E, is required in a particular proportion for normal plant growth, as well as in the phosphate limitation stress using a knockout (KO) insertion mutant, AtelF(iso)4E-1 (page 2, right paragraph 2). Furthermore, the knockout of eIF(iso)4E in A. thaliana plant conferred resistance to infection by several potyviruses (page 2, right paragraph 4) and eIF4E may fulfill the function lacking in eIF(iso)4E for the resistance (page 7, right paragraph 3). Therefore it is not clear which of these known functions have to be missing to be considered “non-functional”. These references also uses gene knockout (KO) mutant for eIF(iso)4E that make the gene that does not encode a functional eukaryotic RNA translation initiation factor, however they have different effect to the plants. Therefore written description is not clear which of these known functions of eIF(iso)4E has to be missing to be considered “non-functional”.
Given the large size and structural diversity associated with the claimed genus, Applicant’s disclosure is not representative of the claimed genus as a whole. This point is particularly relevant because, as discussed above, the prior art speaks to the disconnection between the structure of the broadly claimed variants without reciting or describing any function.
"The test for sufficiency is whether the disclosure of the application relied upon reasonably conveys to one skilled in the art that the inventor had possession of the claimed subject matter as of the filing date." Ariad Pharm, Inc, v EH Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010). To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Lockwood v. Amer. Airlines, ina, 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). "An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations. Lockwood, 107 F.3d at 1572, 41 USPG2d at 1966". While the written description requirement does not demand either examples or an actual reduction, actual "possession" or reduction to practice outside of the specification is not enough. Ariad Pharm, Inc. v. Eli Lilly & Co., 598 F,3d 1336,1352 (Fed. Cir. 2010). Rather, it is the specification itself that must demonstrate possession. Id.
The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. The court stated that, “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 of a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus.” See University of California v. Eli Lilly and Co., 119 F. 3d 1559; 43 USPQ2d 1398, 1406 (Fed. Cir. 1997).
Thus, based on the analysis above, Applicant has not met either of the two elements of the written description requirement as set forth in the court's decision in Eli Lilly. As a result, it is not clear that Applicant was in possession of the claimed genus at the time this application was filed.
Response to Argument
Applicant's arguments filed on 04/23/2025 have been fully considered but they are not persuasive.
Applicant argues Applicants have amended claim 1 as presented, specifically, indicating that the eukaryotic cell is a plant cell (supported throughout the Specification) and further specifying that the protein is of no activity (as seen at least at p. 12 <]{2 of the as-filed Specification). Applicant argues one of ordinary skill in the art can appreciate that a protein with 70% sequence identity may also bear the requisite mutations and cessation of activity without undue experimentation (Response to Rejection, page 5, last paragraph).
Applicant's arguments have been fully considered but they are not persuasive since applicant has not showed the protein is non-0functional protein. Furthermore, applicant has not described any polynucleotide with 70% sequence identity to SEQ ID NO: 20, with the mutation in G2046A would make the protein non-functional causing usable function when the encoded protein is present in the plant cell.
Therefore the written description rejection has been maintained.
Claim Rejections - 35 USC § 112 – Scope of enablement
Since applicant does not teach the mutation cause the “non-functional eIF(iso)4e protein” the Scope of enablement rejection is added, see analysis below.
Claim 1 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a plant cell comprising a mutated eIF(iso)4e sequence of SEQ ID NO:20 having mutation of G2046A encoding G105E substitutions, does not reasonably provide enablement for a plant cell comprising a non-functional eIF(iso)4e protein having mutation of G2046A encoding G105E substitutions. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
An “analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention.” MPEP 2164.01. “A conclusion of lack of enablement means that. . . the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention [i.e. commensurate scope] without undue experimentation.” In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); MPEP 2164.01.
In In re Wands, 858 F.2d 731,8 USPQ2d 1400 (Fed. Cir. 1988), several factors implicated in determination of whether a disclosure satisfies the enablement requirement and whether any necessary experimentation is “undue” are identified. These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731,737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). No single factor is independently determinative of enablement; rather “[i]t is improper to conclude that a disclosure is not enabling based on an analysis of only one of the above factors while ignoring one or more of the others.” MPEP 2164.01. Likewise, all factors may not be relevant to the enablement analysis of any individual claim.
The Breadth of the Claims and nature of invention:
Claim 1 is broadly drawn to any synthetic eukaryotic cell comprising a mutated eIF(iso)4e protein; wherein the mutated eIF(iso)4e protein is encoded by a mutated eIF(iso)4e sequence with at least 70% identity of SEO ID NO: 20; wherein the mutated eIF(iso)4e sequence additionally comprises a G2046A and G105E mutation substitution relative to SEO ID NO:20; and wherein the mutated protein is a plant cell.
Claim 1 requires mutated protein eIF(iso)4e to be non-functional.
Applicant has described the protein was non-functional based on SIFT analysis.
Applicant assert embodiment of the present invention may provide a papaya plant having increased resistance as compared to the wild type papaya plant to the papaya ringspot virus due to a mutation in the eIF4e and/or e1F(iso)4e gene leading to non-functional eIF4e and/or eIF(iso)4E protein (page 3, last paragraph, page 4, first paragraph) as their described utility.
The state of the prior art:
Flanagan et al. teaches the predictive value of SIFT and concludes that SIFT may be useful in prioritizing changes that are likely to cause a loss of protein function, their low specificity means that their predictions should be interpreted with caution and further evidence to support/refute pathogenicity should be sought before reporting novel missense changes (Flanagan, page 533, Abstract).
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Furthermore, Miosge et al. teaches comparison of predicted and actual consequences of missense mutations by SIFT and finds the missense mutation inferred as damaging were only predicted 20% of the time to be accurate (Miosge et al., page E5192, left paragraph 1, page E5191, Table 1) and suggests requirement of direct experimental measurement of the consequences and phenotyping to interpret missense variation (Miosge et al., page E5197, left paragraph 1). Therefore a function of gene or mutation is very unlikely to be predicted accurately by SIFT analysis.
The amount of direction provided by the inventor:
Applicant assert embodiment of the present invention may provide a papaya plant having increased resistance as compared to the wild type papaya plant to the papaya ringspot virus due to a mutation in the eIF4e and/or e1F(iso)4e gene leading to non-functional eIF4e and/or eIF(iso)4E protein (page 3, last paragraph, page 4, first paragraph).
SEQ ID NO: 21 pertains to e1F(iso)4e mutant nucleotide sequence in papaya (papaya mutant line number, M2(0.3)-552 G2046A (GGG->GAG) Gl05E) (page 6).
SEQ ID NO: 25 pertains to mutated eIF(iso)4e amino acid sequence in papaya (papaya line number M2(0.3)-552) (page 6).
Several natural resistance genes against potyviruses, from distinct crops, were shown to encode defective forms of eIF4e and e1F(iso)4e for example pvr2, mol etc. (page 8, last paragraph).
Based on the type of mutation(s), the increase in disease resistance may be 60%-100% compared to wildtype (page 9, paragraph 3).
In an embodiment, if the initial assessment of a mutation in an M2 plant indicates it to be of a desirable nature and in a useful position within the eIF4e and/or e1F(iso)4e gene, then phenotypic analysis of the selected papaya plant containing that mutation maybe pursued using artificial inoculation with the PRSV strain and Enzyme-linked immunosorbent assay (ELISA) tests (page 13, first paragraph).
Applicant teaches the mutation obtained using TILLING method in eIF(iso)4e where the sorting intolerant from tolerant (SIFT) analysis shows result of “Not Tolerated” and SIFT score of “0” (page 21, Table 2, No. 17) for M2(0.3)-552 which is mutant line that comprise nucleotide sequence as of SEQ ID NO: 21 that encodes SEQ ID NO: 25 (Spec, page 6) which is variants of SEQ ID NO: 20 which pertains to e1F(iso)4e gene nucleotide sequence in wild type papaya (Spec, page 6);
Applicant also teaches the mutation obtained using TILLING method in eIF(iso)4e where the SIFT analysis shows result of “Not Tolerated” and SIFT score of “0” for mutant line M2(0.4)-882 where in the mutation is also in exon as in M2(0.3)-552 (page 21, Table 2, No. 2).
Applicant has not taught any example of phenotypic/functional analysis of the M2(0.3)-552 mutant by artificial inoculation.
Applicant has taught an example of phenotypic analysis of the M2(0.4)-882 mutant by artificial inoculation (page 22 and 23) where the results showed that the M2(0.4)-882 is a eIF4e(iso) missense mutant with amino acid changes Y at position 70 to C (Y70C). The table below demonstrates observations (Table 4). Where the Table 4 shows mutant line M2(0.4)-882 has severity score of 4 as Severe mottling+ shoe-stinging and/or stunting which is same as WILD TYPE (Table 3 and 4).
Thus, a mutation of eIF(iso)4e gene that has a G2046A substitution, encoding a G105E mutation in the eIF(iso)4e protein, may not have any disease resistance as showed by M2(0.4)-882 mutant with same SIFT score and analysis and will have same disease severity as WILD TYPE.
The existence of working examples:
The Specification or state of the art does not teach a person with skill in the art how to make and/or use the subject matter within the full scope of these claims because:
Applicant does not teach any function of eIF(iso)4e gene that has a G2046A substitution, encoding a G105E mutation in the eIF(iso)4e protein other than SIFT analysis.
SIFT analysis does not provide any credible function for example mutant line M2(0.4)-882 with same SIFT analysis showing result of “Not Tolerated” and SIFT score of “0” as M2(0.3)-552 which is mutant line that comprise nucleotide sequence of SEQ ID NO: 21 that encodes SEQ ID NO: 25 (page 6), is virus susceptible (see table 4 above).
Lack of a working example is a critical factor to be considered, especially in a case involving an unpredictable and undeveloped art. See MPEP § 2164.
Genetech, 108 F.3d at 1366, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
In the absence of guidance from either the instant disclosure or the art, it would require undue trial and error experimentation for a skilled artisan to use the broadly claimed polynucleotide and polypeptides with a mutation, with no reasonable expectation of success in arriving at a protein variant wherein the mutated eIF(iso)4e protein is non-functional that would have asserted function of virus resistance.
For at least this reason, the Specification does not teach a person with skill in the art how to make and/or use the subject matter within the full scope of these claims.
Summary
No claim is allowed.
Examiner’s Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SANTOSH SHARMA whose telephone number is (571)272-8440. The examiner can normally be reached Mon-Fri 8:00 AM - 5:00 PM.
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/SANTOSH SHARMA/Examiner, Art Unit 1663
/DAVID H KRUSE/Primary Examiner, Art Unit 1663