)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 .
Application Status and Election
The amendments and remarks filed 11/3/25 in response to the office action of 8/4/25 are acknowledge and have been entered. Claims 1, 2, 4-16 are pending. Claim 17 has been canceled. Claims 1, 2, 5-12, and 15, 16 have been amended.
Applicant’s election with traverse of group I (claims 1, 2, 4, 5, 6, 17) in the Remarks filed 7/15/25 remains acknowledged. Applicant elected without traverse the species of signal peptide FAK-alpha factor from S. cerevisiae, with SEQ ID NO. 3, and nucleic acid sequence SEQ ID NO. 13. Claims 7-10 are included within group 1. Claims 11-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Examination on the merits commences on claims 1, 2, 4-10 and 16.
35 USC § 103 and NSDP rejections are maintained. Amendments to claim 16 to remove “or a fragment thereof” necessitate a new §112d rejection.
Examiner acknowledges the Declaration under 37 CFR 1.132 by Dr. Ravi Chandra Beeram filed 11/3/25.
Applicants are informed that the rejections and/or objections of the previous Office action not stated below have been withdrawn from consideration in view of the Applicant' s arguments and/or amendments. Applicant’s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Claim Rejections - 35 USC § 112(d) - NEW
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 16 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 16 recites, “The modified polypeptide as claimed in claim 1
Examiner notes that a product claim with intended use does not carry patentable weight and the contents of the intended use applied to a further dependent claim would also then not carry patentable weight. MPEP 2111.02.II. states, “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.” However, even if the intended use is recited in the body of a product claim, if the intended use does further limit the structure of the product, it is also not considered a limitation.
Claim Rejections - 35 USC § 103 – Modified Maintained
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.
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.
Claim(s) 1 and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over US’927 of record (US10131927, 2018, to Centro de Ingenieria Genetica y Biotecnologia CIGB) and US’332 of record (US20170298332, 2015, currently to Stellenbosch University), and GenBank_β-Fructofuranosidase of record (GenBank_β-Fructofuranosidase, ACCESSION BAB67771, https://www.ncbi.nlm.nih.gov/protein/15620806?sat=3&satkey=5643270, version 9/15/2001, retrieved 7/29/25, printed as pages 1/1 to 1/2), as evidenced by VanWyk of record (Van Wyk, Niel, et al. "Identification of the gene for β-fructofuranosidase from Ceratocystis moniliformis CMW 10134 and characterization of the enzyme expressed in Saccharomyces cerevisiae." BMC biotechnology 13.1 (2013): 100.)
Independent claim 1 is understood to be representative of pending claim scope. The applicable claim interpretation is set forth below.
The preamble of claim 1 recites, “A modified polypeptide”. The peptide is the fructosyltransferase from Aspergillus niger comprising SEQ ID NO.1., and a signal peptide elected species FAK which is the α-factor signal peptide from Saccharomyces cerevisiae (see, specification, p3 line20-end).
Regarding claim 1, US’927 teaches, a recombinant (modified) fructosyltransferase (see, US’927, claim 1). US’927 teaches industrial fructooligosaccharides (FOS) synthesis using β-fructofuranosidase with high transfructosylase activity or FTF, produced mainly by fungi including Aspergillus niger (Col 1 para 3). US’927 further teaches, α-factor signal peptide from Saccharomyces cerevisiae (FAK) (see, FIG. 1., and FIG. 2.). US’927 teaches a signal peptide fused to the fructosyltransferase peptide, which is an α-factor signal sequence from Saccharomyces cerevisiae (see, US’927, FIG. 1., and FIG. 2.) to ease the extracellular secretion of the peptide (see, US’927, Table 1).
US’332 teaches a modified variant of fructosyltransferase from A. japonicus for industrial protein synthesis production (see, US’332, abstract). Examiner notes that Aspergillus niger has been renamed Aspergillus japonicus, as evidenced by VanWyk (pg 8 col2 para 2).
US’927 and US’332, do not teach the sequence (the SEQ ID NO. 1.) of the fructosyltransferase from A. niger.
However, GenBank_β-Fructofuranosidase teaches bete-fructofuranosidase [Aspergillus niger] ACCESSION AB67771 with 100% identity to Applicant’s SEQ ID NO: 1.
At the time of application, one ordinary with the skill in art would combine the teaching of US’927, US’332, VanWyk, and GenBank_β-Fructofuranosidase to arrive at the instantly claimed sequence to produce/express the modified β-Fructofuranosidase polypeptide enzyme. Because US’927 teaches a fructosyltransferase fused to the FAK signal peptide, one of ordinary skill in the art would have found it obvious to substitute the fructosyltransferase with another known fructotransferase, such as the sequence of GenBank_β-Fructofuranosidase, allowing similar and predictably efficacious synthesis of β-Fructofuranosidase with the FAK signal peptide to apply to enhancing methods of industrial protein synthesis.
Claim(s) 16 depends from claim 1. Claim(s) 16 is understood as the modified polypeptide as SEQ ID NO. 1., with signal sequence. However, “for use in the production of fructooligosacharides” is an intended use. Examiner notes that a product claim with intended use does not carry patentable weight and the contents of the intended use applied to a further dependent claim would also then not carry patentable weight. MPEP 2111.02.II. states, “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.” However, even if the intended use is recited in the body of a product claim, if the intended use does further limit the structure of the product, it is also not considered a limitation.
Claim(s) 1, 2, 4-10 and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over US’927 of record (US10131927, 2018, to Centro de Ingenieria Genetica y Biotecnologia CIGB) and of US’332 of record (US20170298332, 2015, currently to Stellenbosch University), and GenBank_β-Fructofuranosidase of record (GenBank_β-Fructofuranosidase, ACCESSION BAB67771, https://www.ncbi.nlm.nih.gov/protein/15620806?sat=3&satkey=5643270, version 9/15/2001, retrieved 7/29/25, printed as pages 1/1 to 1/2), as evidenced by VanWyk of record (Van Wyk, Niel, et al. "Identification of the gene for β-fructofuranosidase from Ceratocystis moniliformis CMW 10134 and characterization of the enzyme expressed in Saccharomyces cerevisiae." BMC biotechnology 13.1 (2013): 100.) as applied to claim 1, and in further view of Yu of record (Yu, Wenwen, et al. "Batch isolation of novel sequences targeting regions of rapid viral variations." Indian J Anim Sci 82.7 (2012): 665-670.).
The teachings of US’927, US’332, GenBank_β-Fructofuranosidase, and VanWyk as applied above for claim 1 are incorporated here.
Claim 2 is depended from claim 1 and recites, sequence of signal sequence FAK which is the α-factor from Saccharomyces cerevisiae (see, specification, p3 line20-end). The sequence is SEQ ID NO. 3.
US’927 teaches a signal peptide fused to the fructosyltransferase peptide, which is an α-factor signal sequence from Saccharomyces cerevisiae (see, US’927, FIG. 1., and FIG. 2.) to ease the extracellular secretion of the peptide (see, US’927, Table 1).
US’927 does not teach the FAK signal protein peptide sequence of SEQ ID NO: 3.
However, Yu et al teaches a signal peptide sequence with GenBank ID: AFJ80404 which has a 100% sequence identity with SEQ ID NO. 3., (see below) and the sequence is from S. cerevisiae α-factor secretion signal peptide to make a chimeric protein (see, attached NPL GenBank ID AFJ80404 file and below).
PNG
media_image1.png
337
807
media_image1.png
Greyscale
At the time of application, one ordinary with the skill in art would combine the teaching of US’927, US’332, VanWyk, GenBank_β-Fructofuranosidase, and Yu to arrive at the instantly claimed sequence to produce/express the modified β-Fructofuranosidase polypeptide enzyme. Because US’927 teaches a fructosyltransferase fused to the FAK signal peptide, one of ordinary skill in the art would have found it obvious to substitute the FAK with another known FAK signal peptide, such as the GenBank ID: AFJ80404 taught by Yu et al, allowing similar and predictably efficacious synthesis to apply to enhancing methods of industrial protein synthesis.
Claim(s) 4 is dependent from claim 1 and claim(s) 5 is dependent from claim 4.
Claim(s) 4-5 is/are understood, the nucleic acid sequence, SEQ ID NO. 13., encoding the β-Fructofuranosidase (SEQ ID NO: 1) with the signal peptide FAK (SEQ ID NO. 3.) as claimed in claim 1 and 2.
US’927 teaches, a FAK signal peptide (see, US’927, FIG. 1., and FIG. 2.). US’927 does not teaches the nucleic acid sequence. Yu et al teaches, a sequence with GenBank ID: JN088769 which has a 99% sequence identity with SEQ ID NO. 13. The only difference in sequence is the 3rd base of the codon 2nd to the last, but it is a silent mutation and code for the same amino acid Lys (K)(see below).
PNG
media_image2.png
519
753
media_image2.png
Greyscale
At the time of application, one ordinary with the skill in art would combine the teaching of US’927, US’332, VanWyk, GenBank_β-Fructofuranosidase, and Yu et al to arrive at the instantly claimed nucleic acid signal sequence to produce the enzyme. Because, US’927 teaches the signal peptide α-factor one of ordinary skill in the art would have found it obvious to substitute the FAK nucleotide sequence with another known signal peptide nucleotide sequence, such as the GenBank ID: AFJ80404 taught by Yu et al., given the obviousness rational applied above for claim 2.
Claim(s) 6 is/are dependent from claim 4, claim(s) 7-8 is/are dependent from claim 6. Claim(s) 6-8 is/are understood, the expression vector (examples pGAPZαA, pGAPZαB, pGAPZαC) and the promotor (AOX1) for the expression/production of beta-fructosyltransferase by expressing SEQ ID NO. 1.
US’927 teaches, a promoter (see, US’927, claim 1) that is AOX1 (see, US927, p1 line4), and plasmid Vector pGAPZαA, pGAPZαB, pGAPZαC (see, US’927, FIG. 1.) for the expression/ production of fructosyltransferase. US’927 does not teach the SEQ ID NO 1., for the expression/production of fructosyltransferase. As stated above GenBank_β-Fructofuranosidase and Yu et al teaches sequences which are 100% identical to SEQ ID NO. 1 and SEQ ID NO. 3., (see, above).
At the time of application, one ordinary with the skill in art would combine the teaching of US’927, US’332, VanWyk, GenBank_β-Fructofuranosidase, and Yu et al to arrive at the instantly claimed sequence with claimed promotor in a claimed vector, to produce the enzyme. Because, US’927 teaches the expression/production fructosyltransferase with a promoter AOX1, in a plasmid from Vector pGAPZaA, pGAPZaB, pGAPZaC, one of ordinary skill in the art would have found it obvious to substitute the nucleotide sequence corresponding to SEC ID NO.1, and SEQ ID NO.3 with other known corresponding nucleotide sequence, taught by GenBank_β-Fructofuranosidase and Yu et al.
Claim(s) 9 is/are dependent from claim 6, and claim(s) 10, is/are dependent from claim 9. Claims(s) 9-10 is/understood, Pichia pastoris yeast host cell of strain GS115 or any strain of the P. pastoris yeast host cell, to harbor the recombinant plasmid for the expression/ production of fructosyltransferase by expressing SEQ ID NO. 1 and SEQ ID NO. 3., In a plasmid vector mentioned in claim 8.
US’927 teaches, Pichia pastoris (see, US’527, claim 2, and 3,) yeast host cell of strain GS115 (see, US’927, FIG. 2) for the expression/production of fructosyltransferase. US’927 does not teach the SEQ ID NO. 1 and SEQ ID NO. 3., for the expression/production of fructosyltransferase. As stated above GenBank_β-Fructofuranosidase and Yu et al teaches sequences which are 100% identical to SEQ ID NO. 1 and SEQ ID NO. 3. (see, above).
At the time of application, one ordinary with the skill in art would combine the teaching of US’927, US’332, GenBank_β-Fructofuranosidase, and Yu et al, to arrive at the instantly claimed P. pastoris yeast host cell of strain GS115 to produce/express the β-fructosyltransferase. One of ordinary skill in the art would have found it obvious to substitute the nucleotide sequence corresponding to SEC ID NO.1, and SEQ ID NO.3 with other known corresponding nucleotide sequence, taught by GenBank_β-Fructofuranosidase and Yu et al, described in the obviousness rationale provided above.
Double Patenting - Maintained
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, 2, 4-10 and 16 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over co-pending Application No. 17779012 (reference application), in view of US’927 of record (US10131927, 2018, to Centro de Ingenieria Genetica y Biotecnologia CIGB) and further in view of US’332 of record (US20170298332, 2015, currently to Stellenbosch University), GenBank_β-Fructofuranosidase of record (GenBank_β-Fructofuranosidase, ACCESSION BAB67771, https://www.ncbi.nlm.nih.gov/protein/15620806?sat=3&satkey=5643270, version 9/15/2001, retrieved 7/29/25, printed as pages 1/1 to 1/2), claim 1 as evidenced by VanWyk of record (Van Wyk, Niel, et al. "Identification of the gene for β-fructofuranosidase from Ceratocystis moniliformis CMW 10134 and characterization of the enzyme expressed in Saccharomyces cerevisiae." BMC biotechnology 13.1 (2013): 100.) as applied to claim 1, and in further view of Yu of record (Yu, Wenwen, et al. "Batch isolation of novel sequences targeting regions of rapid viral variations." Indian J Anim Sci 82.7 (2012): 665-670.).
Regarding instant claims 1, 2, 4-10 and 16-17, Examiner notes that Aspergillus niger has been renamed Aspergillus japonicus, as evidenced by VanWyk (pg 8 col2 para 2). Examiner also notes that instant SEQ ID NO: 1 is 99.5% identical to reference SEQ ID NO: 1 with a single mismatch.
The Copending claims teach:
1. (Currently Amended) A modified polypeptide, wherein the modified polypeptide comprises fructosyltransferase of Aspergillus japonicus comprising the amino acid sequence of SEQ ID NO: 1 fused to a signal peptide, wherein the signal peptide is alpha-factor of Saccharomyces cerevisiae (FAK), alpha-factor full of S.cerevisiae (FAKS), alpha factor T of S. cerevisiae (AT), alpha-amylase of Aspergillus niger(AA), glucoamylase of Asperigillus awamori (GA), inulinase of Kluyveromyces maxianus (IN), invertase of S. cerevisiae (IV), killer protein of S. cerevisiae (KP), lysozyme of Gallus (LZ), or serum albumin of Homo sapiens (SA).
2. (Currently Amended) The modified polypeptide as claimed in claim 1, wherein:[[a.]]a) FAK comprises the amino acid sequence of SEQ ID NO: 3 or variants thereof;[[b.]]b FAKS comprises the amino acid sequence of SEQ ID NO: 4 or variants thereof;[[c.]] AT comprises the amino acid sequence of SEQ ID NO: 5;[[d.]]dl AA comprises the amino acid sequence of SEQ ID NO: 6 or variants thereof;[[e.]]} GA comprises the amino acid sequence of SEQ ID NO: 7 or variants thereof;[[f.]]comprises the amino acid sequence of SEQ ID NO: 8;[[g.]]g} IV comprises the amino acid sequence of SEQ ID NO: 9;[[h.]]hl KP comprises the amino acid sequence of SEQ ID NO: 10 or variants thereof;[[i.]]il LZ comprises the amino acid sequence of SEQ ID NO: 11;and [[j.]]j) SA comprises the amino acid sequence of SEQ ID NO: 12;and wherein the signal peptide enables the extracellular secretion of the modified polypeptide comprising the amino acid sequence of SEQ ID NO: 1.
4. (Original) A nucleic acid encoding the peptide as claimed in claim 1.
5. (Currently Amended) The nucleic acid as claimed in claim 4, wherein the nucleic acid comprises the sequence of SEQ ID NO: 13, SEQ ID NO:
14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21,or SEQ ID NO: 22.
6. (Currently Amended) An expression vector comprising the nucleic acid as claimed in claim 4 operably linked to a promoter.
7. (Currently Amended) The expression vector as claimed in claim 6, wherein the promoter for fructosyltransferase gene is a promoter for the gene: alcohol oxidase 1 (AOX1), alcohol dehydrogenase (ADH3), dihydroxyacetone phosphatase (DAS), formaldehyde dehydrogenase (FLD1), L-rhamnonate dehydratase (LRA3), thiamine biosynthesis protein (THI11), glyceraldehyde-3-phosphate dehydrogenase (GAP), GTPase involved in secretion (YPT1), translation elongation factor-1 alpha (TEF1),glycosylphosphatidyl inositol (GCw14), or phosphoglycerate kinase (PGK1).
8. (Currently Amended) The expression vector as claimed in claim 6, wherein the expression vector is pPICZaA, pPICZaB, pPICZaC, pGAPZaA, pGAPZaB, pGAPZaC, pPIC3, pPIC3.5, pPIC3.5K, PA0815, pPIC9, pPIC9K, IL- D2, orpHIL-S 1= and wherein the expression vector is configured for secretory or intracellular expression of fructosyltransferase from Aspergillus japonicus as set forth in SEQ ID NO: 1.
9. (Currently Amended) A recombinant Pichia pastoris host cell comprising [[an]]the expression vector as claimed in claim 6.
10. (Currently Amended) The recombinant Pichia pastoris host cell as claimed in claim 9, wherein the host cell is Pichia pastoris Mut+, Pichia pastoris Mut S, Pichia pastoris Mut-, Pichia pastoris KM71H, Pichia pastoris KM71, Pichia pastoris SMD1168H, Pichia pastoris SMD1168, Pichia pastoris X33, or Pichia pastoris GS115.
11. (Currently Amended) A method of producing [[a]]the recombinant Pichia pastoris host cell according to claim 9 capable of expressing fructosyltransferase of Aspergillus japonicus comprising the amino acid sequence of SEQ ID NO: 1, the process comprising the steps of:[[a.]])synthesizing a modified nucleic acid encoding fructosyltransferase from Aspergillus japonicus comprising the sequence as set forth in SEQ ID NO: 1;[[b.]]b constructing a vector comprising the modified nucleic acid; and [[c.]] transforming a Pichia pastoris host cell with the vector of step (b) to obtain a recombinant Pichia pastoris host cell.
12. (Withdrawn - Currently Amended) A process for expressing fructosyltransferase of Aspergillus japonicus comprising the sequence as set forth in SEQ ID NO: 1 according to claim 1, the process comprising:[[a.]]) culturing recombinant Pichia pastoris host cells capable of expressing fructosyltransferase of Aspergillus japonicus comprising the sequence as set forth in SEQ ID NO: 1 in a suitable fermentation medium to obtain a fermentation broth;[[b.]]b harvesting supernatant from the fermentation broth, wherein the supernatant contains recombinant p-fructofuranosidase; and purifying recombinant 3-fructofuranosidase.
16. (Currently Amended) The modified polypeptide as claimed in claim 1 or a fragment thereof for use in the production of fructooligosaccharides.
It would have been obvious to modify the copending claims to arrive at the instant claimed invention, given the rationale applied above.
This is a provisional rejection because the copending claims have not yet been patented.
Response to Arguments
Examiner acknowledges the Declaration under 37 CFR 1.132 by Dr. Ravi Chandra Beeram filed 11/3/25. Dr. Ravi Chandra Beeram declares that experimental data presented herein demonstrate that, compared to the β-fructofuranosidase of Aspergillus niger lacking the native signal peptide (Δ19aa-fructofuranosidase) and fused with alpha-factor of Saccharomyces cerevisiae signal peptide (α-factor signal peptide), the full length β-fructofuranosidase of Aspergillus niger (full length β-fructofuranosidase) fused with α-factor signal peptide exhibits surprising and unexpected advantages that render the claims of the application non-obvious.
Applicants argue (Remarks pg 9) that the cited references fail to teach or suggest a modified protein comprising the claimed Beta-fructofuranosidase of Aspergillus niger comprising the amino acid sequence of SEQ ID NO: 1 and the signal peptide as instantly claimed. Applicants argue (Remarks pg 10) that US '927 and US '332 describe polypeptides (wild type or mutants) devoid of native signal peptides fused to heterologous signal peptides for the expression of the polypeptide and that supporting references do not remedy this failure. Applicants further argue (Remarks pg 7-12), that a person of ordinary skill in the art would not have been motivated to fuse a signal peptide to a “full-length” β-fructofuranosidase. Applicants argue that as routinely practiced in the art, when a heterologous signal peptide is fused to a protein, the native signal peptide is removed before fusing the heterologous signal peptide, and therefore a skilled artisan would not have been motivated to retain the native signal peptide of the fused protein and further fuse a heterologous signal peptide. Applicants further argue (Remarks pg 12-13) that that a prima facie case of obviousness can be rebutted by showing that the claimed invention exhibits one or more superior properties or advantages that a person of ordinary skill in the art would have found surprising or unexpected.
Applicant’s arguments have been thoroughly reviewed and found unpersuasive for the following reasons: In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395; B/E Aerospace, Inc. v. C&D Zodiac, Inc., 962 F.3d 1373, 1379, 2020 USPQ2d 10706 (Fed. Cir. 2020); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atl. & P. Tea Co. v. Supermarket Equip. Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950). Additionally, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant arguments and declaration relies (i.e., a modified signal peptide with “full-length” β-fructofuranosidase still containing the native signal peptide and further fuse a heterologous signal peptide) are not recited in the rejected claim(s). Claim 1 discloses a modified Beta-fructofuranosidase protein of SEQ ID NO: 1 where SEQ ID NO: 1 is 100% identical and well-known in the art, as taught by GenBank_β-Fructofuranosidase and the FAK secretion signal is well-known in the art. Examiner notes that although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Examiner notes that US’927 teaches a signal peptide fused to the fructosyltransferase peptide, which is an α-factor signal (FAK) sequence from Saccharomyces cerevisiae (FIG. 1., and FIG. 2.) in order to ease the extracellular secretion of the peptide (see, US’927, Table 1). Yu et al teaches a signal peptide sequence with GenBank ID: AFJ80404 which has a 100% sequence identity with the claimed FAK SEQ ID NO. 3 where the sequence is a S. cerevisiae α-factor secretion signal peptide fused to make a chimeric protein. It would therefore be predictable that such as FAK sequence would predictably enhance the secretion of the claimed β -fructofuranosidase of Aspergillus niger comprising the amino acid sequence of SEQ ID NO: 1 taught by GenBank_β-Fructofuranosidase.
Therefore, Examiner maintains the obviousness rejection of record such that one ordinary with the skill in art could combine the reference teachings to arrive at the instantly claimed sequence to produce/express the modified β-Fructofuranosidase polypeptide enzyme. Because US’927 teaches a fructosyltransferase fused to the FAK signal peptide, one of ordinary skill in the art would have found it obvious to substitute the fructosyltransferase with another known fructotransferase, such as the sequence of GenBank_β-Fructofuranosidase which is 100% identical to the claimed SEQ ID NO: 1, allowing similar and predictably efficacious synthesis of β-Fructofuranosidase with the FAK signal peptide, which is well known as a booster secretion sequence, in order to enhance methods of industrial protein synthesis.
Conclusion
No claims are allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN CHARLES MCKILLOP whose telephone number is (703)756-1089. The examiner can normally be reached Mon-Fri 8:30-5:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner' s supervisor, Jennifer Dunston, can be reached on (571) 272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JOHN CHARLES MCKILLOP/Examiner, Art Unit 1637
/EKATERINA POLIAKOVA-GEORGANTAS/Primary Examiner, Art Unit 1637