DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Amendment Status
2. The amendment to the specification filed August 7, 2026 has been entered. Claims filed May 23, 2024 has been entered. Claims 1-11 are under consideration in this Office Action.
Specification
3. The objection to the disclosure is withdrawn in view of Applicants Amendments to the specification.
Maintained Grounds of Rejection
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
4. Claims 1-11 are rejected under 35 U.S.C. 103 as being unpatentable over Jang et al., (WO 2011075677 published June 2011; priority to Dec 2010) in view of Koike et al., (Industrial Biotechnology 9, no. 6:352-367. Published Dec. 1, 2013).
The claims are drawn to a protease deficient host cell comprising at least one inactivation in a chromosomal gene comprising a nucleic acid sequence encoding a polypeptide having at least 90% sequence identity with the amino acids 402-533 of SEQ ID NO: 13, wherein the protease deficient host cell has a lower expression level of aspartic proteases, serine proteases, glutamic proteases, and metalloproteases, compared to the expression level of aspartic proteases, serine proteases, glutamic proteases, and metalloproteases of a corresponding host cell in which the chromosomal gene is not inactivated.
Jang et al., teach mutants of a parent Trichoderma strain, comprising a polynucleotide encoding a polypeptide and one or more (several) genes selected from the group consisting of a first subtilisin-like serine protease gene, a first aspartic protease gene, a trypsin-like serine protease gene, a second subtilisin-like serine protease gene, and a second aspartic protease gene, wherein the one or more (several) genes are modified rendering the mutant strain deficient in the production of one or more (several) enzymes selected from the group consisting of a first subtilisin-like serine protease, a first aspartic protease, a trypsin-like serine protease, a second subtilisin-like serine protease, and a second aspartic protease, respectively, compared to the parent Trichoderma strain when cultivated under identical conditions. The present invention also relates to methods of producing a polypeptide in such mutants and methods for producing such mutants [abstract]. The enzyme-deficient Trichoderma mutant strain may be constructed by reducing or eliminating expression of one or more (several) genes selected from the group consisting of a subtilisin-like serine protease gene, an aspartic protease gene, and a trypsin-like serine protease gene using methods well known in the art, such as insertions, disruptions, replacements, or deletions [para 64]. Inactivated resulting in no expression or a weaker promoter may be substituted for the native promoter sequence to reduce expression of the coding sequence [para 65]. The Trichoderma mutant strains may be constructed by gene deletion techniques to eliminate or reduce expression of a gene. Gene deletion techniques enable the partial or complete removal of the gene thereby eliminating their expression [para 65]. The mutants of Trichoderma strains may contain additional modifications, e.g., deletions or disruptions, of other genes, which may encode substances detrimental to the production, recovery, or application of a polypeptide of interest [para 106]. The Trichoderma strain further comprises a modification, e.g., disruption or deletion, of one or more (several) genes encoding a proteolytic activity selected from the group consisting of an aminopeptidase, dipeptidylaminopeptidase, tripeptidylaminopeptidase, carboxypeptidase, metalloprotease, cysteine protease, and vacuolar protease [para 107]. Thus teaching the M1 and M28 aminopeptidase family of claim 3.
The term “deficient” is defined herein as a Trichoderma mutant strain that produces no detectable activity of one or more (several) enzymes selected from the group consisting of a subtilisin-like serine protease, an aspartic protease, and a trypsin-like serine protease compared to the parent Trichoderma strain when cultivated under identical conditions, or, in the alternative, produces preferably at least 25% less, more preferably at least 50% less, even more preferably at least 75% less, and most preferably at least 95% less of one or more (several) enzymes selected from the group consisting of a subtilisin-like serine protease, an aspartic protease, and a trypsin-like serine protease than the parent Trichoderma strain when cultivated under identical conditions [para 37]. Jang et al., teach Subtilisin-like serine protease: The term “subtilisin-like serine protease” is defined herein as a protease with a substrate specificity similar to subtilisin that uses a serine residue for catalyzing the hydrolysis of peptide bonds in peptides and proteins [para 34]. The term “aspartic protease” is defined herein as a protease that uses an aspartate residue for catalyzing the hydrolysis of peptide bonds in peptides and proteins. For purposes of the present invention, aspartic endopeptidase activity [para 35]; thus teaching claim 2. The deletion of one or more (several) of the subtilisin-like serine protease gene, the aspartic protease gene, and/or the serine protease gene may be partial or complete. The modification results in a decrease in or elimination (inactivation) of expression of the subtilisin-like serine protease gene, the aspartic protease gene, the serine protease gene, or a combination thereof. In a preferred aspect, one or more (several) of the subtilisin-like serine protease gene, the aspartic protease gene, and the serine protease gene are inactivated [para 58]. The mutants of Trichoderma strains may contain additional modifications, e.g., deletions or disruptions, of other genes, which may encode substances detrimental to the production, recovery, or application of a polypeptide of interest [para 106]. Thus teaching claims 4-5 and 7.
The Trichoderma mutant strains are cultivated in a nutrient medium for production of the polypeptide of interest using methods known in the art. The cultivation takes place in a suitable nutrient medium comprising carbon and nitrogen sources and inorganic salts, using procedures known in the art. Suitable media are available from commercial suppliers or may be prepared according to published compositions [para 111]. Thus teaching the inorganic salts as stabilizers just as recited by claims 8-9.
The secreted polypeptide can be recovered directly from the medium. If the polypeptide is not secreted, it may be obtained from cell lysates [para 111]. Thus teaching the protein preparation as recited by instant claims 10-11.
Therefore, Jang et al., teach a protease deficient host cell comprising at least one inactivation in a chromosomal gene comprising, wherein the protease deficient host cell has a lower expression level of aspartic proteases, serine proteases, glutamic proteases, and metalloproteases, compared to the expression level of aspartic proteases, serine proteases, glutamic proteases, and metalloproteases of a corresponding host cell in which the chromosomal gene is not inactivated; however Jang et al., does not specifically recite the nucleic acid sequence encoding a polypeptide having at least 90% sequence identity with the amino acids 402-533 of SEQ ID NO: 13.
Koike et al., teach Trichoderma reesei is a key fungus for industrial production [abstract]. Koike et al., a wide variety of filamentous fungi, including T. reesei, are used as production hosts for a multitude of proteins. Strains of T. reesei are reported to produce a complex mix of cellulolytic enzymes in excess of 100 g/L. The amount of the secreted enzymes is significant as it is not only elevated for cellulase production, but also more generally for protein secretion [Introduction]. Knowledge of the genetic factors responsible for the cellulase hyper-producing phenotype is important for improving biomass saccharification as well as for enhancing the expression of heterologous proteins. Genome-wide analysis of the mutations lays a genetic foundation that may be translated into more economical production of enzymes needed for renewable bioenergy applications [Introduction]. The amount of cellulolytic enzymes produced by T. reesei is significantly high, not only for cellulase production in fungi but also for protein production by microorganisms in general. Much research has been conducted to reveal the biology that underlies its high protein production and secretion mechanisms. Studies involving functional genomic analysis of T. reesei have continued to increase [Conclusion].
Therefore, it would have been prima facie obvious at the time of applicants’ invention to apply Koike et al’s T reesei strain and sequence for Jang et al’s protease deficient host cell comprising at least one inactivation in a chromosomal gene in order to provide a host cell known to protease deficient and able to produce and secrete enzymes. Jang et al., already teach a protease deficient T reesei host cell comprising at least one inactivation in a chromosomal gene wherein the protease deficient host cell has a lower expression level of aspartic proteases, serine proteases, glutamic proteases, and metalloproteases. One of ordinary skill in the art would have a reasonable expectation of success by incorporating the T reesei host cell where several genes are modified rendering the mutant strain deficient in the production of one or more (several) enzymes selected from the group consisting of a first subtilisin-like serine protease, a first aspartic protease, a trypsin-like serine protease, a second subtilisin-like serine protease, and a second aspartic protease.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". It is well known to take a
protease deficient T reesei host cell comprising at least one inactivation in a chromosomal gene comprising a nucleic acid sequence encoding a polypeptide having at least 90% sequence identity with the amino acids 402-533 of SEQ ID NO: 13, wherein the protease deficient host cell has a lower expression level of aspartic proteases, serine proteases, glutamic proteases, and metalloproteases, compared to the expression level of aspartic proteases, serine proteases, glutamic proteases, and metalloproteases of a corresponding host cell in which the chromosomal gene is not inactivated, where there is no change in the respective function of the host cell or the expression mechanics, thus the combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Thus, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Sequence Alignment with SEQ ID NO:13
A0A024S366_HYPJR
ID A0A024S366_HYPJR Unreviewed; 825 AA.
AC A0A024S366;
DT 09-JUL-2014, integrated into UniProtKB/TrEMBL.
DT 09-JUL-2014, sequence version 1.
DT 08-OCT-2025, entry version 25.
DE RecName: Full=Clr5 domain-containing protein {ECO:0000259|Pfam:PF14420};
GN ORFNames=M419DRAFT_85889 {ECO:0000313|EMBL:ETR99517.1};
OS Hypocrea jecorina (strain ATCC 56765 / BCRC 32924 / NRRL 11460 / Rut C-30)
OS (Trichoderma reesei).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Hypocreaceae; Trichoderma.
OX NCBI_TaxID=1344414 {ECO:0000313|EMBL:ETR99517.1, ECO:0000313|Proteomes:UP000024376};
RN [1] {ECO:0000313|Proteomes:UP000024376}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 56765 / BCRC 32924 / NRRL 11460 / Rut C-30
RC {ECO:0000313|Proteomes:UP000024376};
RX DOI=10.1089/ind.2013.0015;
RA Koike H., Aerts A., LaButti K., Grigoriev I.V., Baker S.E.;
RT "Comparative genomics analysis of Trichoderma reesei strains.";
RL Ind. Biotechnol. 9:352-367(2013).
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DR EMBL; KI911156; ETR99517.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A024S366; -.
DR KEGG; trr:M419DRAFT_85889; -.
DR HOGENOM; CLU_008755_0_0_1; -.
DR OrthoDB; 194358at2759; -.
DR Proteomes; UP000024376; Unassembled WGS sequence.
DR InterPro; IPR025676; Clr5_dom.
DR PANTHER; PTHR38788; CLR5 DOMAIN-CONTAINING PROTEIN; 1.
DR PANTHER; PTHR38788:SF3; CLR5 DOMAIN-CONTAINING PROTEIN; 1.
DR Pfam; PF14420; Clr5; 1.
PE 4: Predicted;
FT DOMAIN 367..419
FT /note="Clr5"
FT /evidence="ECO:0000259|Pfam:PF14420"
FT REGION 302..367
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 302..311
FT /note="Low complexity"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 325..335
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 825 AA; 92235 MW; CE24243B7AA2A6B5 CRC64;
Query Match 100.0%; Score 695; Length 825;
Best Local Similarity 100.0%;
Matches 132; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RPSREQVPAEAWEQYKSTIRTLYLEERKPLKEVMSVMAEQYGFQATPKMYKTRFSQWGFV 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 359 RPSREQVPAEAWEQYKSTIRTLYLEERKPLKEVMSVMAEQYGFQATPKMYKTRFSQWGFV 418
Qy 61 KNNTEEEVKRLLSMKFQRDAEGKVSEFVRNGRVVNLGTYLKRKGVTEYDLVDFELPADLP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 419 KNNTEEEVKRLLSMKFQRDAEGKVSEFVRNGRVVNLGTYLKRKGVTEYDLVDFELPADLP 478
Qy 121 AHIRCRTPTPPP 132
||||||||||||
Db 479 AHIRCRTPTPPP 490
Response to Arguments
5. Applicant's arguments filed August 7, 2026 have been fully considered but they are not persuasive. The rejection of claims 1-11 under 35 U.S.C. 103 as being unpatentable over Jang et al., in view of Koike et al., is maintained for reasons of record.
Applicants argue that Jang et al., does not teach or such reducing the production levels of more than one endogenous protease by inactivation of a single gene, such as a global protease regulator. However, Applicants attention is directed to the instant claims. The instant claims do not recite inactivation of a single gene such as a global protease regulator. Instead, the instant claims recite …a protease deficient host cell comprising at least one inactivation in a chromosomal gene comprising a nucleic acid sequence encoding a polypeptide having at least 90% sequence identity with the amino acids 402-533 of SEQ ID NO: 13, wherein the protease deficient host cell has a lower expression level of aspartic proteases, serine proteases, glutamic proteases, and metalloproteases, compared to the expression level of aspartic proteases, serine proteases, glutamic proteases, and metalloproteases of a corresponding host cell in which the chromosomal gene is not inactivated. 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 relies i.e., a single gene such as a global protease regulator are not recited in the rejected claims. 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). Therefore, the argument is not persaussive.
Applicants urge that Koike et al., do not anything specific about protease regulators. In response to applicant's arguments against the Koike et al., reference individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, Jang et al., teach a protease deficient host cell comprising at least one inactivation in a chromosomal gene comprising, wherein the protease deficient host cell has a lower expression level of aspartic proteases, and/or serine proteases, compared to the expression level of aspartic proteases, and/or serine proteases, of a corresponding host cell in which the chromosomal gene is not inactivated; however Jang et al., does not specifically recite the nucleic acid sequence encoding a polypeptide having at least 90% sequence identity with the amino acids 402-533 of SEQ ID NO: 13. One of ordinary skill in the art would have a reasonable expectation of success by incorporating the T reesei host cell where several genes are modified rendering the mutant strain deficient in the production of one or more (several) enzymes selected from the group consisting of a first subtilisin-like serine protease, a first aspartic protease, a trypsin-like serine protease, a second subtilisin-like serine protease, and a second aspartic protease.
Applicants argue that the Examiner must identify a reason that would have prompted a person of ordinary skill in the art in the relevant field to combine the elements in the way the now claimed invention does. In this case, it would have been prima facie obvious at the time of applicants’ invention to apply Koike et al’s T reesei strain and sequence for Jang et al’s protease deficient host cell comprising at least one inactivation in a chromosomal gene in order to provide a host cell known to protease deficient and able to produce and secrete enzymes, just as Koike et al., described. Moreover, it is well known to take a protease deficient T reesei host cell comprising at least one inactivation in a chromosomal gene comprising a nucleic acid sequence encoding a polypeptide having at least 90% sequence identity with the amino acids 402-533 of SEQ ID NO: 13, wherein the protease deficient host cell has a lower expression level of aspartic proteases, serine proteases, glutamic proteases, and metalloproteases, compared to the expression level of aspartic proteases, serine proteases, glutamic proteases, and metalloproteases of a corresponding host cell in which the chromosomal gene is not inactivated, where there is no change in the respective function of the host cell or the expression mechanics, thus the combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention.
Finally, Applicants assert that the prior art references do not teach the pea1 gene or its role as a protease regulator. Jang et al., taught the enzyme-deficient Trichoderma mutant strain may be constructed by reducing or eliminating expression of one or more (several) genes while Koike et al., teach the naturally occurring wild type SEQ ID NO:13 which is the full-length Pea1 protein. Koike et al., teach genome-wide analysis of the mutations regarding the more economical production of enzymes. In response to applicant's argument, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Therefore, Applicants arguments are not found persuasive and the rejection is maintained.
Double Patenting
6. 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.
7. Claims 1-2, 4 and 7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of U.S. Patent No.10,883,131. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to a protease deficient host cell comprising at least one inactivation in a chromosomal gene comprising a nucleic acid sequence encoding a polypeptide having at least 90% sequence identity with the amino acids 402-533 of SEQ ID NO: 13, wherein the protease deficient host cell has a lower expression level of aspartic proteases, serine proteases, glutamic proteases, and metalloproteases, compared to the expression level of aspartic proteases, serine proteases, glutamic proteases, and metalloproteases of a corresponding host cell in which the chromosomal gene is not inactivated.
The patented clams are drawn to a host cell comprising at least one inactivated chromosomal gene wherein the at least one inactivated chromosomal gene comprises a nucleic acid sequence encoding a polypeptide comprising a sequence having at least 90% sequence identity with the amino acids 402-533 of SEQ ID NO: 13; the at least one inactivated chromosomal gene is inactivated by disruption, inhibition of translation or transcription of the chromosomal gene, at least partial deletion, truncation, deletion, insertion, mutation, or silencing, by RNAi, or by CRISPR/Cas9 technology;
and the host cell has reduced protease activity compared to the host cell without said
inactivation.
Therefore, both sets of claims recite the same protease deficient host cell comprising at least one inactivation in a chromosomal gene comprising a nucleic acid sequence encoding a polypeptide having at least 90% sequence identity with the amino acids 402-533 of SEQ ID NO: 13 having reduced protease activity compared to the host cell without said inactivation. Accordingly, the instant claims and patented claims are not patentably distinct.
Response to Arguments
8. Applicant's arguments filed August 7, 2026 have been fully considered but they are not persuasive. Applicants requested the rejection be held in abeyance until the status of the claimed subject matter is finally resolved. Therefore, the rejection will be maintained.
Double Patenting
9. Claims 1, 6 and 8-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No.12,031,168. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to a protein preparation comprising secreted recombinant protein and a protein preparation comprising the protease deficient host cell comprising at least one inactivation in a chromosomal gene comprising a nucleic acid sequence encoding a polypeptide having at least 90% sequence identity with the amino acids 402-533 of SEQ ID NO: 13, wherein the protease deficient host cell has a lower expression level of aspartic proteases, serine proteases, glutamic proteases, and metalloproteases, compared to the expression level of aspartic proteases, serine proteases, glutamic proteases, and metalloproteases of a corresponding host cell in which the chromosomal gene is not inactivated.
Both sets of claims recite protein preparations comprising additional reagents. Both sets of claims recite a protein preparation comprising spent culture broth from production of a heterologous recombinant protein of interest in a host cell having at least one inactivated chromosomal gene wherein: the at least one inactivated chromosomal gene comprises a nucleic acid sequence encoding a polypeptide comprising a sequence having at least 90% sequence identity with the amino acids 402-533 of SEQ ID NO: 13; the at least one inactivated chromosomal gene is inactivated by disruption; and the host cell has reduced protease activity on the heterologous recombinant protein of interest in the host cell compared to protease activity on the heterologous recombinant protein of interest in the host cell without said inactivation, and wherein the spent culture broth has a reduced amount of endogenous proteases compared to a corresponding spent culture broth produced in a host cell with an intact nucleic acid sequence encoding a polypeptide comprising a sequence having at least 90% sequence identity with the amino acids 402-533 of SEQ ID NO: 13; and wherein the heterologous recombinant protein of interest has an increased stability in the spent culture broth compared to a protein preparation produced in the same host cell without said inactivation.
Therefore, the instant claims and patented claims are not patentably distinct.
Response to Arguments
10. Applicant's arguments filed August 7, 2026 have been fully considered but they are not persuasive. Applicants requested the rejection be held in abeyance until the status of the claimed subject matter is finally resolved. Therefore, the rejection will be maintained.
Pertinent Art
11. The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure.
In cell culture, inorganic salts and stabilizers are essential for maintaining the physiological environment that supports cell survival, growth, and function.
Inorganic Salts
See: Koike H., Aerts A., LaButti K., Grigoriev I.V., Baker S.E.; "Comparative genomics analysis of Trichoderma reesei strains."; Ind. Biotechnol. 9:352-367(2013). Teaching 100% sequence match
See also US Patents 5,000,939; 4,120,950. WO2015187697 and WO 2016132021. CA 2994320.
Conclusion
12. No claims allowed.
13. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JA-NA A HINES whose telephone number is (571)272-0859. The examiner can normally be reached Monday thru Thursday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor Peter Paras, can be reached on 571-272-4517. 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).
/JANA A HINES/Primary Examiner, Art Unit 1645
Prosecution Insights