DETAILED ACTION
Status of Application
Claims 1-3, 5-8, 10, 11, 14, 24 and 34 are pending
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A preliminary amendment of claim 11, and cancellation of claims 4, 9, 12-13, 15-23, 25-33, and 35-38 as submitted in a communication filed on 06/05/2026 is acknowledged.
Applicant’s election without traverse of Group 1, claims 1-3, 5-8, 10-11, drawn to a polypeptide having fumonisin esterase activity, as submitted in communication filed on 06/05/2026 is acknowledged.
Applicant’s species election without traverse of SEQ ID NO: 14 as submitted in communication filed on 06/05/2026 is acknowledged
Claims 6-8, 14, 24, and 34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 without traverse in the reply filed on 06/05/2026.
Claims 1-3, 5, and 11 are at issue and will be examined to the extent they encompass the elected invention.
Priority
Acknowledgment is made of applicant’s claim for domestic priority under 35
U.S.C. 119 (e) to provisional Application No. 63/303394 filed on 01/26/2022.
This is the US national application which entered the national stage from
Application No. PCT/IB2023/050690 filed on 01/26/2023.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 08/07/2024
are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The drawings submitted on 07/23/2024 have been reviewed and are accepted by
the examiner for examination purposes.
Claim Rejections - 35 USC § 112(a) or First Paragraph (pre-AIA )
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.
Claims 1-3 are 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
As stated in MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow.
Claims 1-3 are directed in part to a genus of polypeptides having fumonisin esterase activity having at least 70% identity with the amino acid sequence of SEQ ID NO: 1 wherein said polypeptides have increased residual fumonisin esterase activity, when measured after a heat challenge at a temperature of at least 37°C for at least 1 minute, when compared to the control polypeptide comprising the amino acid of SEQ ID NO: 3.
In University of California v. Eli Lilly & Co., 43 USPQ2d 1938, the Court of Appeals for the Federal Circuit has held that “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials”. As indicated in MPEP § 2163, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show that Applicant was in possession of the claimed genus. In addition, MPEP § 2163 states that a representative number of species means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The claims encompass a large genus of polypeptides having fumonisin esterase activity which are substantially unrelated in structure. A sufficient written description of polypeptides may be achieved by a recitation of a representative number of polypeptide sequences or a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. However, in the instant case, there is no recited structural feature which is representative of all the members of the genus of polypeptides with the recited limitations, and there is no information as to which are the structural elements of the polypeptides with the recited limitations that are essential for the recited increase of residual fumonisin esterase activity, when measured after a heat challenge at a temperature of at least 37°C for at least 1 minute, when compared to the control polypeptide comprising the amino acid of SEQ ID NO: 3, or a correlation between structure and function which would provide those unknown structural features. Furthermore, while one could argue that the species disclosed is representative of the structure of all the members of the genus of polypeptide sequences required, it is noted that the art teaches examples of how even highly structurally similar polypeptide sequences can have different functions and/or activity levels. For example, Das et al. (The FEBS Journal 281.24 (2014): 5602-5621) teach proteins with high sequence and structural similarity can have different functions (Page 5603 [2]). Therefore, since minor structural differences may result in changes affecting polypeptide function, and no additional information correlating structure with the desired functional characteristics has been provided, one cannot reasonably conclude that the species disclosed, including the listed polypeptide having the recited sequences, are representative of the structure of all the polypeptides having fumonisin esterase activity having at least 70% identity with the amino acid sequence of SEQ ID NO: 1 with the recited claim limitations, that can have the increased residual fumonisin esterase activity, when measured after a heat challenge at a temperature of at least 37°C for at least 1 minute, when compared to the control polypeptide comprising the amino acid of SEQ ID NO: 3, that is required by the claimed product. Therefore, one of ordinary skill in the art would not recognize from the disclosure that Applicant was in possession of the claimed invention.
Claims 1-3 are 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 polypeptide having fumonisin esterase activity that comprises SEQ ID NO: 14, does not reasonably provide enablement for any polypeptide having fumonisin esterase activity having at least 70% sequence identity with the protein of SEQ ID NO: 1 with the claimed limitations, wherein the polypeptide has increased residual fumonisin esterase activity, when measured after a heat challenge at a temperature of at least 37°C for at least 1 minute, when compared to the control polypeptide of SEQ ID NO: 3. 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.
Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2nd 1400 (Fed. Cir. 1988)) as follows: 1) quantity of experimentation necessary, 2) the amount of direction or guidance presented, 3) the presence and absence of working examples, 4) the nature of the invention, 5) the state of prior art, 6) the relative skill of those in the art, 7) the predictability or unpredictability of the art, and 8) the breadth of the claims. The factors which have led the Examiner to conclude that the specification fails to teach how to make and/or use the claimed invention without undue experimentation, are addressed in detail below.
The breadth of the claims. Claims 1-3 broadly encompass polypeptides having at least 70% sequence identity with the protein of SEQ ID NO: 1 with the claimed limitations, wherein the polypeptide has increased residual fumonisin esterase activity, when measured after a heat challenge at a temperature of at least 37°C for at least 1 minute, when compared to the control polypeptide of SEQ ID NO: 3. The enablement provided is not commensurate in scope with the claims due to the lack of knowledge regarding the structure/common features required in any polypeptide having the recited sequence identity percentage and fumonisin esterase activity. In the instant case, the specification enables the polypeptide of SEQ ID NO: 14.
The amount of direction or guidance presented and the existence of working examples. The specification discloses the polypeptide of SEQ ID NO: 14 as a working example. However, the specification fails to provide any clue as to the structural elements required in any polypeptide having fumonisin esterase activity that has increased residual fumonisin esterase activity, when measured after a heat challenge at a temperature of at least 37°C for at least 1 minute, when compared to the control polypeptide comprising the amino acid of SEQ ID NO: 3. No correlation between structure and function has been presented.
The state of prior art, the relative skill of those in the art, and the predictability or unpredictability of the art. The structure of a polypeptide determines its structural and functional properties. While the art discloses a limited number of polypeptides with fumonisin esterase activity, neither the specification nor the art provide a correlation between structure and function such that one of skill in the art can envision the structure of any polypeptide with fumonisin esterase activity that can have increased residual fumonisin esterase activity, when measured after a heat challenge at a temperature of at least 37°C for at least 1 minute, when compared to the control polypeptide comprising the amino acid of SEQ ID NO: 3. The art clearly teaches that highly structurally similar polypeptide sequences can have different functions and/or activity levels. For example, Das et al. (The FEBS Journal 281.24 (2014): 5602-5621) teach proteins with high sequence and structural similarity can have different functions (Page 5603 [2]). Therefore, it is unpredictable to determine which polypeptides having at least 70% sequence identity with the polypeptide of SEQ ID NO: 1 will have the desired fumonisin esterase activity.
The quantity of experimentation required to practice the claimed invention based on the teachings of the specification. A polypeptide having 70% sequence identity with the polypeptide of SEQ ID NO: 1 allows for any combination of 147 amino acid modifications within SEQ ID NO: 1 (147 = 0.3x490; SEQ ID NO: 1 has 490 amino acids). The total number of variants of a polypeptide having a specific number of amino acid substitutions can be calculated from the formula N!x19A/(N-A)!/A!, where N is the length in amino acids of the reference polypeptide and A is the number of allowed substitutions. Thus, the total number of variants having at least 70% sequence identity with the polypeptide of SEQ ID NO: 1 that result from amino acid substitutions is 490!x19147/(490-147)!/147! or 3.67x10316 variants. While methods of determining polypeptide function and activity were known in the art at the time of the invention, it was not routine in the art to screen by a trial and error process for an essentially infinite number of polypeptides to find the polypeptide with the desired function. In the absence of (i) a rational and predictable scheme for selecting those polypeptides most likely to have the desired functional features, (ii) a correlation between structure and the recited function, one of skill in the art would have to test an infinite number of polypeptides to find those with the desired fumonisin esterase activity.
Therefore, taking into consideration the extremely broad scope of the claim, the lack of guidance, the amount of information provided, the high degree of unpredictability regarding structural modifications and effects in function, one of ordinary skill in the art would have to go through the burden of undue experimentation in order to practice the claimed invention. Thus, Applicant has not provided sufficient guidance to enable one of ordinary skill in the art to make and use the invention in a manner reasonably correlated with the scope of the claims.
Double Patenting
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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 5, and 11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 7 of U.S. Patent No. US 20240084244 A1 (hereby referred to as ‘224). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 1-3, 5, and 11 of the instant application, ‘244 claim 7 teaches: “The recombinant yeast host cell of claim 6, wherein: the polypeptide having phospholipase activity comprises an amino acid sequence of SEQ ID NO. 1 or 4, is a variant of the amino acid sequence of SEQ ID NO: 1 or 4 having phospholipase activity, or is a fragment of the amino acid sequence of SEQ ID NO: 1 or 4 having phospholipase activity; the polypeptide having fumonisin esterase activity comprises an amino acid sequence of SEQ ID NO: 21, is a variant of the amino acid sequence of SEQ ID NO: 21 having fumonisin esterase activity, or is a fragment of the amino acid sequence of SEQ ID NO: 21 having fumonisin esterase activity; or the polypeptide having alpha-amylase activity comprises an amino acid sequence of SEQ ID NO: 23, is a variant of the amino acid sequence of SEQ ID NO: 23 having alpha-amylase activity, or is a fragment of the amino acid sequence of SEQ ID NO: 23 having alpha-amylase activity”. A sequence alignment of instant SEQ ID NO: 14 and SEQ ID NO: 21 of ‘244 were a 100% identity match. See alignment below. Furthermore, the specification of ‘244 discloses that the recombinant yeast host cell having the polypeptide having fumonisin esterase activity that comprises SEQ ID NO: 21 can be submitted to a temperature of between about 40° C. to about 70 ° C (Page 23 [111]). Therefore, claim 7 of ‘244 anticipates instant claims 1-3, 5, and 11.
RESULT 1
BLL60559
ID BLL60559 standard; protein; 490 AA.
XX
AC BLL60559;
XX
DT 01-SEP-2022 (first entry)
XX
DE Fumonisin esterase protein, SEQ ID 21.
XX
KW Fumonisin B1 protein; Fumonisin esterase; expression;
KW genetically engineered microorganism; propagation; recombination.
XX
OS Unidentified.
XX
CC PN WO2022162559-A2.
XX
CC PD 04-AUG-2022.
XX
CC PF 26-JAN-2022; 2022WO-IB050686.
XX
PR 26-JAN-2021; 2021US-0141807P.
XX
CC PA (DANS-) DANSTAR FERMENT AG.
XX
CC PI Wang Z, Ranade A, Argyros A, Froehlich A, Rice CF;
XX
DR WPI; 2022-98233X/067.
XX
CC PT New recombinant yeast host cell comprising first genetic modification,
CC PT and second genetic modification for increasing growth rate of recombinant
CC PT yeast host cell, useful to express heterologous polypeptide or
CC PT overexpress native polypeptide.
XX
CC PS Claim 7; SEQ ID NO 21; 73pp; English.
XX
CC The present invention relates to a recombinant yeast host cell useful for
CC expressing heterologous polypeptides or overexpressing native
CC polypeptides. The recombinant yeast host cell comprises (i) a first
CC genetic modification for (a) expressing a heterologous polypeptide or
CC over-expressing a native polypeptide and (b) a signal sequence
CC operatively associated with the heterologous or native polypeptide, and
CC (ii) a second genetic modification for increasing the growth rate of the
CC recombinant yeast host cell compared to the growth rate of a control
CC yeast host cell, where the heterologous or native polypeptide has
CC phospholipase activity of SEQ ID NO. 1 or 4, (see BLL60539 or BLL60542),
CC fumonisin esterase activity or alpha-amylase activity. The second genetic
CC modification is a modification in a yeast protein secretory and
CC trafficking pathway or a modulation in the expression of a gene involved
CC in polypeptide folding, glycosylation, and degradation in the endoplasmic
CC reticulum (ER). The invention further discloses an aerobic process for
CC propagating the recombinant yeast host cell by culturing the recombinant
CC yeast host cell in a culture medium under conditions. The recombinant
CC yeast host cells are useful for expressing a heterologous polypeptide or
CC overexpressing a native polypeptide.
XX
SQ Sequence 490 AA;
Query Match 100.0%; Score 2588; Length 490;
Best Local Similarity 100.0%;
Matches 490; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 FPVRRTDLGQVQGLAGDVISFRGIPYAAPPVGDLRWKPPQHARPWAGVRPATQFGSDCFG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 FPVRRTDLGQVQGLAGDVISFRGIPYAAPPVGDLRWKPPQHARPWAGVRPATQFGSDCFG 60
Qy 61 AAYLRKGSLAPGVSEDCLYLNVWAPSDAKPGQYPVMVWVYGGGFAGGTAAMPYYDGEALA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AAYLRKGSLAPGVSEDCLYLNVWAPSDAKPGQYPVMVWVYGGGFAGGTAAMPYYDGEALA 120
Qy 121 RQGVVVVTFNYRTNIFGFFAHPGLSRESPTGTSGNYGLLDILAALRWVQSNARAFGGDPG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 RQGVVVVTFNYRTNIFGFFAHPGLSRESPTGTSGNYGLLDILAALRWVQSNARAFGGDPG 180
Qy 181 RVTVFGESAGASAIGLLLTSPLSKGLFRGAILESPGLTRPLATLADSAASGERLDADLSR 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 RVTVFGESAGASAIGLLLTSPLSKGLFRGAILESPGLTRPLATLADSAASGERLDADLSR 240
Qy 241 LRSTDPATLMARADAARPASRDLRKPRPIGPIVDGHVLPQTDSDAIA AGQLAPVPVLIGT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LRSTDPATLMARADAARPASRDLRKPRPIGPIVDGHVLPQTDSDAIA AGQLAPVPVLIGT 300
Qy 301 NADEGRAFLGRAPIETPADYQAYLEALFGDQAAAVAACYPLDGRATPKEMVARIFGDNQF 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 NADEGRAFLGRAPIETPADYQAYLEALFGDQAAAVAACYPLDGRATPKEMVARIFGDNQF 360
Qy 361 NRGVSAFSEALVRHGVPVWRYQFIGNTEDGRAPATHGAEIPYVFGVFKLDELGLFDWPPE 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 NRGVSAFSEALVRHGVPVWRYQFIGNTEDGRAPATHGAEIPYVFGVFKLDELGLFDWPPE 420
Qy 421 GPTLADRALCQLMSSAWVRFAKNGDPAGDALTWPAYSTGKSTMTFGPEGRAAVVSPGPSI 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 GPTLADRALCQLMSSAWVRFAKNGDPAGDALTWPAYSTGKSTMTFGPEGRAAVVSPGPSI 480
Qy 481 PSCADGVKAG 490
||||||||||
Db 481 PSCADGVKAG 490
Conclusion
No claim is in condition for allowance.
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/S.L.S./Examiner, Art Unit 1652
/ROBERT B MONDESI/Supervisory Patent Examiner, Art Unit 1652
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