DETAILED ACTION
Status of the Application
Claims 1, 10, 18, 20-25, 32 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 .
Applicant’s amendment of claims 1, 10, 18, 20, 23-25, addition of claim 32, cancellation of claims 2-8, 11-17, 19, 26-31 and amendments to the specification as submitted in a communication filed on 1/7/2026 is acknowledged.
Applicant elected without traverse Group I, claims 1-8, 10-25, 31, drawn in part to a subtilisin variant and a composition comprising said variant, and the election of the combination of positions 39, 74 and 99, including the combination of substitutions 39E, 74D and 99R, in a communication filed on 5/8/2025 is acknowledged. In view of the election of the combination of substitutions 39E, 74D and 99R, in view of the amendment of claim 10, which is now limited to variants that include these three substitutions, and the fact that a variant of the polypeptide of SEQ ID NO: 1 having at least 90% sequence identity to the polypeptide of SEQ ID NO: 18 which comprises the substitutions that correspond to the substitutions S39E, N74D, and S99R in the polypeptide of SEQ ID NO: 85 is free of the prior art, claim 10 has been rejoined for examination on the merits. Claim 32 is directed to the elected invention.
Claims 1, 10, 18, 20-25 and 32 are at issue and will be examined only to the extent they encompass the elected invention.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Specification
The first paragraph of the specification was objected to because it did not provide the current status of related applications (e.g., now US Patent No. X). In view of Applicant’s amendment, this objection is hereby withdrawn.
Claim Rejections – Improper Markush Grouping
Claims 1-8, 12-25 and 31 were rejected on the basis that they contain an improper Markush grouping of alternatives. In view of Applicant’s amendment of claim 1, which is now directed to variants of the polypeptide of SEQ ID NO: 1 having at least 90% sequence identity to the polypeptide of SEQ ID NO: 18 which comprises the substitutions that correspond to the substitutions S39E, N74D, and S99R in the polypeptide of SEQ ID NO: 85, this rejection is hereby withdrawn.
Claim Rejections - 35 USC § 101
Claims 1-8, 12-20 were rejected under 35 U.S.C. 101 because the claimed invention was directed to natural phenomenon without significantly more. In view of Applicant’s amendment of claim 1 which now requires a protein having at least 90%sequence identity to the polypeptide of SEQ ID NO: 18 and the proteins of Goddette et al. (GenBank accession No. P29599, 10/1/1993), Garcia-Ramon et al. (GenBank accession No. KLK97980, 6/1/2015), and Kudo et al. (GenBank accession No. GAK08459, 5/21/2014) do not have the recited % sequence identity, this rejection is hereby withdrawn.
Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA )
Claims 1, 10, 18, 20-25 remain rejected and new claim 32 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 pre-AIA the applicant regards as the invention. New grounds of rejection are necessitated by amendment.
Claim 1 (claims 10, 18, 20-25, 32 dependent thereon) is indefinite in the recitation of “and comprising amino acid substitutions at positions corresponding to positions in the polypeptide of SEQ ID NO: 85 of S039E-N74D-S099R….improved thermostability in detergent” for the following reasons. The term “amino acid substitutions at positions corresponding to positions in the polypeptide of SEQ ID NO: 85 of” implies that the following phrase refers to positions. However, the following term refers to substitutions. In addition, it is unclear if the substitutions recited are substitutions that correspond to substitutions in the polypeptide of SEQ ID NO: 85. In addition, the term “a reference subtilisin having the amino acid sequence of SEQ ID NO: 85” encompasses a genus of proteins and is not limited to a single defined protein. Please note that the term encompasses not only the subtilisin of SEQ ID NO: 85 but any fusion protein that comprises SEQ ID NO: 85. Therefore, the protein used as a reference point is variable. Furthermore, it is totally unclear as to what is the meaning of the term “thermostability in detergent”. If the intended limitation is “having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 18, wherein said variant comprises substitutions that correspond to substitutions S039E, N74D and S99R in the polypeptide of SEQ ID NO: 85, wherein said variant has one or more improved properties compared to the subtilisin of SEQ ID NO: 85 selected from the group consisting of improved protease activity, improved cleaning activity, and improved thermostability”, the claim should be amended accordingly. Correction is required.
Claim 10 is indefinite in the recitation of “wherein said variant comprises an amino acid sequence comprising one or more amino acid substitutions selected from A037T-S039E-N074D-S099R-V102I, S126T….A037T….S158T-G160S-N242D; and combinations thereof” for the following reasons. The recitation of positions as they relate to substitutions is meaningless in the absence of the sequence identifier associated with those positions. In addition, while it appears that the substitutions to select from are sets of substitutions at different substitutions, they all require the substitutions S039E-N074D-S099R. Other sets of substitutions have overlapping substitutions. As such, it is unclear as to how one could have combinations of the sets of substitutions. For example, if set one comprises substitutions A-B-C-D and another set comprises substitutions X-B-C-Y, it is unclear as to how one could have a combination of substitutions A-B-C-D-X-B-C-Y (two times substitution B and two times substitution C). If the intended limitation is “wherein said variant comprises a combination of substitutions that correspond to substitutions in the polypeptide of SEQ ID NO: 85, wherein said combination is selected from the group consisting of A037T-S039E-N074D-S099R-V102I, S126T….; and A037T….S158T-G160S-N242D”, the claim should be amended accordingly. For examination purposes, claim 10 will be interpreted as a duplicate of claim 1. Correction is required.
Claim 18 is indefinite in the recitation of “wherein said variant has a PI>1…wherein said…variant has a BMI and/or egg stain cleaning PI >1….stability PI > 1”, “cleaning performance in detergent” and “thermostability in detergent” for the following reasons. It is unclear as to what “PI” is and how being greater than one is associated with protease activity, cleaning performance and thermostability. In addition, it is unclear as to which is the meaning of the terms “cleaning performance in detergent” and “thermostability in detergent”. For examination purposes, it will be assumed that the claim is a duplicate of claim 1 as interpreted above. Correction is required.
Claim 20 (claims 21-25 and 32 dependent thereon) is indefinite in the recitation of “comprising the one or more isolated subtilisin variants of claim 1” for the following reasons. There is no antecedent basis for “the one or more” isolated subtilisin variants of claim 1. For examination purposes, it will be assumed that claim 20 is directed to a composition that comprises the isolated subtilisin variant of claim 1. Correction is required.
Claim 23 is indefinite in the recitation of “further comprises one or more calcium…one or more enzyme stabilizer; from about 0.001% to about 1.0 weight% of said variant, …one or more additional enzymes or enzyme variants selected from….serine proteases, and combinations thereof” for the following reasons. The term “about” encompasses a range which includes values which are higher and lower than the recited reference value (i.e., 0.001%, 1.0%). The term “from X to Y”, implies a range where X and Y are the endpoints. Therefore, in the absence of a clear definition of what is encompassed by the term “about”, the term "from about X to about Y" is unclear and confusing because X and Y are endpoints which are undefined ranges. In addition, it is unclear if the enzyme variant is a structural variant or a functional variant. Therefore, it is unclear if the composition is required to have, for example, a structural variant of an acyl transferase, wherein said variant may or may not have acyl transferase activity, or a functional variant of an acyl transferase. If the enzyme variant refers to a functional variant, it is unclear as to which is the functional variant of an enzyme that has been already defined by its enzymatic activity (i.e., function). For example, which is the function of a functional variant of an acyl transferase. If the functional variant is one that has acyl transferase activity, how is this enzyme variant any different from the recited acyl transferase? Furthermore, it is unclear as to which are the combinations being referred to by the term “combinations thereof”. Does the term refer to combinations of the enzymes previously recited, or does the term refer to combinations of all the elements recited in the claim that should be present in the compositions, such as calcium ions, enzyme stabilizers, bleaching agents, and enzymes? Correction is required.
When amending the claims, applicant is advised to carefully review all examined claims and make the necessary changes to ensure proper antecedent basis and dependency.
Claim Rejections - 35 USC § 112(a) or First Paragraph (pre-AIA )
Claims 1, 18, 20-25 remain rejected and claims 10 and 32 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. This rejection as it relates to claim 32 is necessitated by amendment.
This rejection has been discussed at length in the prior Office action. It is maintained and further applied to claims 10 and 32 for the reasons set forth below.
Applicant argues that claim 1 has been amended to recite that the variants have at least 90% sequence identity with the polypeptide of SEQ ID NO: 18 and 3 specific substitutions. Applicant states that in view of the amendment and the description of several variants of the polypeptide of SEQ ID NO: 18, one of skill in the art would reasonably conclude that Applicant had possession of the claimed invention.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the instant rejection or avoid the rejection of claims 10 and 32. The Examiner acknowledges the amendments made to claim 1. However, the Examiner disagrees with Applicant’s contention that the entire genus of proteins is adequately described. Claims 1, 10, 18, 20-25 and 32 are directed in part to a genus of variants of the polypeptide of SEQ ID NO: 18 having at least 90% sequence identity to the polypeptide of SEQ ID NO: 18, wherein said variants have three substitutions that correspond to substitutions S39E, N74D, and S99R in the polypeptide of SEQ ID NO: 85 wherein said variants can have protease activity or any function. Please note that claim 1 as amended requires improved properties in the alternative. Therefore, improved protease activity is not required. As such, the variants of the claims are not required to have protease activity. A polypeptide having 90% sequence identity with the polypeptide of SEQ ID NO: 18 allows for any combination of 27 amino acid modifications within SEQ ID NO: 18 (27 = 0.1x269). 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 90% sequence identity to the polypeptide of SEQ ID NO: 18 that result from amino acid substitutions is 269!x1927/(269-27)!/27! (SEQ ID NO: 18 have 269 amino acids) or 3.21x1071 variants. While the specification in the instant application discloses the structure of a limited number of species of the recited genus of variants of the polypeptide of SEQ ID NO: 18 that have protease activity and have enhanced properties compared to the polypeptide of SEQ ID NO: 85, it provides no clue as to the structural elements required in any protease as recited, nor does it teach which structural elements of the proteins disclosed are required in any subtilisin for such protein to have the desired protease activity with enhanced thermostability and enhanced cleaning activity. No disclosure of a structure/function correlation has been provided which would allow one of skill in the art to recognize which variants of the polypeptide of SEQ ID NO: 18 have the desired enhanced properties.
Furthermore, while one could argue that the few species disclosed are representative of the structure of all the members of the genus, it is noted that the art teaches several examples of how even highly structurally homologous polypeptides can have different enzymatic activities. See the teachings of Witkowski et al., Tang et al. and Seffernick et al. previously discussed. Therefore, since minor structural differences may result in changes affecting function, and no additional information correlating structure with the desired functional characteristics has been provided, one cannot reasonably conclude that the few species disclosed are representative of the structure of all the variants required by the claims. As such, one cannot reasonably conclude that the entire genus of variants required by the claims are adequately described by the teachings of the specification and/or the prior art.
Claims 1, 18, 20-25 remain rejected and claims 10 and 32 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) a variant of the polypeptide of SEQ ID NO: 18 that has protease activity, wherein said variant comprises all of SEQ ID NO: 18 except for substitutions that correspond to substitutions S39E, N74D and S39R in the polypeptide of SEQ ID NO: 85, and (b) a composition comprising the polypeptide of (a), does not reasonably provide enablement for (i) variants of the polypeptide of SEQ ID NO: 18 having at least 90% sequence identity to the polypeptide of SEQ ID NO: 18, wherein said variants can have any function, or (ii) compositions comprising said variants. 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.
This rejection has been discussed at length in the prior Office action. It is maintained and further applied to claims 10 and 32 for the reasons set forth below.
Applicant argues that as amended, the claims are directed to variants have at least 90% sequence identity with the polypeptide of SEQ ID NO: 18 and 3 specific substitutions. Applicant states that the specification provides ample disclosure and guidance such that one of skilled in the art can practice the claimed invention without undue experimentation. Applicant states that the specification provides variants of the polypeptide of SEQ ID NO: 18 having the desired enhanced properties. Applicant states that the specification provides assay methods by which to analyze variants for the desired enhanced properties. Applicant states that the specification provides parameters for determining sequence identity.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the instant rejection or avoid the rejection of claims 10 and 32. The Examiner acknowledges the amendments made to the claims as well as the teachings of the specification. However, the Examiner disagrees with Applicant’s assertions that the entire scope of the claims is fully enabled by the teachings of the specification and/or the prior art.
As previously indicated, claims 1, 10, 18, 20-25 and 32 are directed in part to a genus of variants of the polypeptide of SEQ ID NO: 18 having at least 90% sequence identity to the polypeptide of SEQ ID NO: 18, wherein said variants have three substitutions that correspond to substitutions S39E, N74D, and S99R in the polypeptide of SEQ ID NO: 85 wherein said variants can have protease activity or any function. As indicated above, claim 1 as amended requires improved properties in the alternative. Therefore, improved protease activity is not required. As such, the variants of the claims are not required to have protease activity.
It is reiterated herein that the number of structural variants of the polypeptide of SEQ ID NO: 18 having 90% sequence identity to the polypeptide of SEQ ID NO: 18 is essentially infinite. The specification is silent with regard to the structural features required in any variant of the polypeptide of SEQ ID NO: 18 that have the desired enhanced characteristics. No structure/function correlation has been provided to recognize which variants of the polypeptide of SEQ ID NO: 18 have the desired functional characteristics. The specification fails to disclose how to use those variants of the polypeptide of SEQ ID NO: 18 that do not have protease activity. While it is agreed that enzymatic assays and methods to determine sequence identity are known in the art, in the absence of (i) a rational and predictable scheme for selecting those proteins most likely to have the desired functional features, and/or (ii) a correlation between structure and protease activity, one of skill in the art would have to test an essentially infinite number of proteins to determine which ones have the desired functional characteristics, and find a use for those variants that meet the recited structural limitations but do not have protease activity. This is not routine experimentation. Therefore, contrary to Applicant’s assertions, the entire scope of the claims is not fully enabled by the teachings of the specification and/or the prior art. .
Claim Rejections - 35 USC § 102 (AIA ).
Claims 1-8, 12-20 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Goddette et al. (GenBank accession No. P29599, 10/1/1993). In view of Applicant’s amendment of claim 1, which now requires a protein having at least 90% sequence identity to the polypeptide of SEQ ID NO: 18, and the protein of Goddette et al. does not have the required sequence identity, this rejection is hereby withdrawn.
Claims 1-8, 12, 14-20 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kudo et al. (GenBank accession No. GAK08459, 5/21/2014). In view of Applicant’s amendment of claim 1, which now requires a protein having at least 90% sequence identity to the polypeptide of SEQ ID NO: 18, and the protein of Kudo et al. does not have the required sequence identity, this rejection is hereby withdrawn.
Claims 1-8, 12, 14-20 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Garcia-Ramon et al. (GenBank accession No. KLK97980, 6/1/2015). In view of Applicant’s amendment of claim 1, which now requires a protein having at least 90% sequence identity to the polypeptide of SEQ ID NO: 18, and the protein of Garcia-Ramon et al. does not have the required sequence identity, this rejection is hereby withdrawn.
Claims 1-8, 12-25 and 31 were rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Minning et al. (US Patent No. 7507569, issued 3/24/2009). The variant of SEQ ID NO: 2 of Minning et al. has 88.1% sequence identity to the polypeptide of SEQ ID NO: 18. The variant of SEQ ID NO: 4 of Minning et al. has 86.2% sequence identity to the polypeptide of SEQ ID NO: 18. In view of Applicant’s amendment of claim 1, which now requires a protein having at least 90% sequence identity to the polypeptide of SEQ ID NO: 18, and the proteins of Minning et al. do not have the required sequence identity, this rejection is hereby withdrawn.
Double Patenting
Claims 1, 18, 20-25 remain rejected and claims 10 and 32 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over (i) claims 1-19 of U.S. Patent No. 11,421,189 (common inventors Babe, Goedegebuur, and Pricelius; different assignee), (ii) claims 1-9 of U.S. Patent No. 11,946,081 (common inventors Babe, Goedegebuur, Mulder and Pricelius), and (iii) claims 1-10 of U.S. Patent No. 11,499,146 (common inventors Babe, Bott, Estell, Yao, Scotcher, Goedegebuur, Mulder and Pricelius).
Applicant has requested the Office hold these rejections in abeyance until allowable subject matter is indicated.
Applicant’s arguments have been fully considered. In view of the fact that no arguments have been filed traversing the Examiner’s position and no terminal disclaimer has been filed, these rejections are maintained.
Claims 1, 10, 18, 20-25 and 32 are directed in part to a (A) variant of the polypeptide of SEQ ID NO: 18 having at least 90% sequence identity to the polypeptide of SEQ ID NO: 18, wherein said variant has substitutions that correspond to substitutions S39E, N74D, and S99R in the polypeptide of SEQ ID NO: 85, (B) a detergent composition comprising the variant of (A), wherein said composition is a laundry detergent, a fabric softening composition, a dishwashing detergent, or a hard surface cleaning detergent, and (C) a composition comprising the variant of (A), wherein said composition comprises calcium, phosphate, boron, an enzyme stabilizer, and/or additional enzymes selected from alpha-amylases, beta-amylases, cellulases, cutinases, galactanases, laccases, lipases, mannases, oxidases, pectinases, peroxidases, proteases, xylanases, metalloproteases, and serine proteases, wherein the composition can be a granular composition, a powder, a solid, a bar, a liquid composition, a tablet, or a paste. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
Claims 1-19 of U.S. Patent No. 11,421,189 are directed in part to an automatic dishwashing cleaning composition that comprises variants of the polypeptide of SEQ ID NO: 1 having at least 90% sequence identity to the polypeptide of SEQ ID NO: 1, wherein said variants comprise substitutions that correspond to substitutions X039E, X074D, and X099R in the polypeptide of SEQ ID NO: 1, wherein said variants have protease activity, wherein said cleaning composition is phosphate free, comprises bleaching agents (bleach activator and/or bleach catalyst), and an amylase. SEQ ID NO: 1 of U.S. Patent No. 11,421,189 is identical to SEQ ID NO: 85 of the instant application. An alignment of the protein of SEQ ID NO: 18 and the variant of claims 1-19 of U.S. Patent No. 11,421,189 shows this variant is 97% sequence identical to the polypeptide of SEQ ID NO: 18 of the instant application. See alignment below.
Therefore, the composition of claims 1-19 of U.S. Patent No. 11,421,189 anticipate the variants and compositions of claims 1, 10, 18, 20-25 and 32 of the instant application.
Query = SEQ ID NO:18
Sbjct = variant of SEQ ID NO:1 - US Patent No. 11,421,189
NW Score Identities Positives Gaps
1344 260/269(97%) 265/269(98%) 0/269(0%)
Query 1 QQTVPWGITRVQAPAVHNRGITGSGVRVAILDSGISTHEDLNVRGGVSFVPGEPTTADLN 60
QQTVPWGITRVQAPAVHNRGITGSGVRVAILDSGIS HEDLN+RGG SFVPGEPTTADLN
Sbjct 1 QQTVPWGITRVQAPAVHNRGITGSGVRVAILDSGISAHEDLNIRGGASFVPGEPTTADLN 60
Query 61 GHGTHVAGTVAALNNSIGVVGVAPSADLYAVKVLGANGRGSVSGIAQGLEWAAANNMHIA 120
GHGTHVAGTVAAL+NSIGV+GVAP+A+LYAVKVLGANGRGSVSGIAQGLEWAA NNMHIA
Sbjct 61 GHGTHVAGTVAALDNSIGVIGVAPNAELYAVKVLGANGRGSVSGIAQGLEWAATNNMHIA 120
Query 121 NMSLGSDAPSSTLERAVNYATSRDVLVIAATGNNGSGSVGYPARYANAMAVGATDQNNRR 180
NMSLGSD PSSTLERAVNYATSRDVLVIAATGNNGSGSVGYPARYANAMAVGATDQNNRR
Sbjct 121 NMSLGSDFPSSTLERAVNYATSRDVLVIAATGNNGSGSVGYPARYANAMAVGATDQNNRR 180
Query 181 ANFSQYGTGIDIVAPGVNVQSTYPGNRYVSMNGTSMATPHVAGAAALVKQRYPSWNATQI 240
ANFSQYGTGIDIVAPGVNVQSTYPGNRYVSMNGTSMATPHVAGAAALVKQRYPSWNATQI
Sbjct 181 ANFSQYGTGIDIVAPGVNVQSTYPGNRYVSMNGTSMATPHVAGAAALVKQRYPSWNATQI 240
Query 241 RNHLKNTATNLGNSSQFGSGLVNAEAATR 269
RNHLKNTATNLGNSSQFGSGLVNAEAATR
Sbjct 241 RNHLKNTATNLGNSSQFGSGLVNAEAATR 269
Claims 1-9 of U.S. Patent No. 11,946,081 are directed in part to a subtilisin variant having at least 90% sequence identity with the polypeptide of SEQ ID NO: 1, wherein said variant comprises substitutions corresponding to substitutions S039E, S099R in the polypeptide of SEQ ID NO: 1, and further comprises the substitution that correspond to substitution N074D in the polypeptide of SEQ ID NO: 1 (claim 2, variant S039E-T056Y-N074D-S099R-S126A-D127E-F128G), and a composition that comprises said subtilisin variant, wherein said composition comprises a detergent and additional enzymes including amylases, calcium ions, zinc ions, and bleaching agents, wherein said composition is phosphate-free or boron-free, wherein the composition is in the form of granules, liquid, solid, bar, gel , paste, or in a unit dose composition, wherein the composition comprises laundry detergent (textile cleaning). SEQ ID NO: 1 of U.S. Patent No. 11,946,081 is identical to SEQ ID NO: 85 of the instant application. An alignment of the protein of SEQ ID NO: 18 and the variant of claims 1-9 of U.S. Patent No. 11,946,081 (claim 2, variant S039E-T056Y-N074D-S099R-S126A-D127E-F128G ) shows this variant is 96% sequence identical to the polypeptide of SEQ ID NO: 18 of the instant application. See alignment below. Therefore, the variant and compositions of claims 1-9 of U.S. Patent No. 11,946,081 anticipate the variants and compositions of claims 1, 10, 18, 20-25 and 32 of the instant application as written/interpreted.
Query = SEQ ID NO:18
Sbjct = variant of SEQ ID NO:1 - US Patent No. 11,946,081
NW Score Identities Positives Gaps
1332 257/269(96%) 264/269(98%) 0/269(0%)
Query 1 QQTVPWGITRVQAPAVHNRGITGSGVRVAILDSGISTHEDLNVRGGVSFVPGEPTTADLN 60
QQTVPWGITRVQAPAVHNRGITGSGVRVAILDSGIS HEDLN+RGG SFVPGEPT ADLN
Sbjct 1 QQTVPWGITRVQAPAVHNRGITGSGVRVAILDSGISAHEDLNIRGGASFVPGEPTYADLN 60
Query 61 GHGTHVAGTVAALNNSIGVVGVAPSADLYAVKVLGANGRGSVSGIAQGLEWAAANNMHIA 120
GHGTHVAGTVAAL+NSIGV+GVAP+A+LYAVKVLGANGRGSVSGIAQGLEWAA NNMHIA
Sbjct 61 GHGTHVAGTVAALDNSIGVIGVAPNAELYAVKVLGANGRGSVSGIAQGLEWAATNNMHIA 120
Query 121 NMSLGSDAPSSTLERAVNYATSRDVLVIAATGNNGSGSVGYPARYANAMAVGATDQNNRR 180
NMSLG++ PSSTLERAVNYATSRDVLVIAATGNNGSGSVGYPARYANAMAVGATDQNNRR
Sbjct 121 NMSLGAEGPSSTLERAVNYATSRDVLVIAATGNNGSGSVGYPARYANAMAVGATDQNNRR 180
Query 181 ANFSQYGTGIDIVAPGVNVQSTYPGNRYVSMNGTSMATPHVAGAAALVKQRYPSWNATQI 240
ANFSQYGTGIDIVAPGVNVQSTYPGNRYVSMNGTSMATPHVAGAAALVKQRYPSWNATQI
Sbjct 181 ANFSQYGTGIDIVAPGVNVQSTYPGNRYVSMNGTSMATPHVAGAAALVKQRYPSWNATQI 240
Query 241 RNHLKNTATNLGNSSQFGSGLVNAEAATR 269
RNHLKNTATNLGNSSQFGSGLVNAEAATR
Sbjct 241 RNHLKNTATNLGNSSQFGSGLVNAEAATR 269
Claims 1-10 of U.S. Patent No. 11,499,146 are directed in part to variants of the polypeptide of SEQ ID NO: 18 having at least 90% sequence identity to the polypeptide of SEQ ID NO: 18 and protease activity, wherein said variants comprise substitutions that correspond to substitutions S039E, S099R and F128A in the polypeptide of SEQ ID NO: 85, wherein said variants can also comprise the substitution that correspond to the substitution N074D in the polypeptide of SEQ ID NO: 85 (claim 2), and a composition comprising said variants, wherein the composition is a laundry detergent composition that is phosphate-free or boron-free, wherein said composition is in the form of granules, powder, gel, tablet, paste, or is a unit dose composition, wherein said composition comprises calcium ions, zinc ions, enzyme stabilizers, bleaching agents, and enzymes, including amylases. SEQ ID NO: 18 and SEQ ID NO: 85 of U.S. Patent No. 11,499,146 and SEQ ID NO: 18 and SEQ ID NO: 85 of the instant application are identical. An alignment of the protein of SEQ ID NO: 18 and the variant of claims 1-10 of U.S. Patent No. 11,499,146 (S039E, S099R and F128A) shows this variant is 99% sequence identical to the polypeptide of SEQ ID NO: 18 of the instant application. See alignment below. Therefore, the variants and compositions of claims 1-10 of U.S. Patent No. 11,499,146 anticipate the variants and compositions of claims 1, 10, 18, 20-25 and 32 of the instant application as written/interpreted.
Query = SEQ ID NO:18
Sbjct = variant of SEQ ID NO:18 - US Patent No. 11,499,146
NW Score Identities Positives Gaps
1372 268/269(99%) 269/269(100%) 0/269(0%)
Query 1 QQTVPWGITRVQAPAVHNRGITGSGVRVAILDSGISTHEDLNVRGGVSFVPGEPTTADLN 60
QQTVPWGITRVQAPAVHNRGITGSGVRVAILDSGISTHEDLNVRGGVSFVPGEPTTADLN
Sbjct 1 QQTVPWGITRVQAPAVHNRGITGSGVRVAILDSGISTHEDLNVRGGVSFVPGEPTTADLN 60
Query 61 GHGTHVAGTVAALNNSIGVVGVAPSADLYAVKVLGANGRGSVSGIAQGLEWAAANNMHIA 120
GHGTHVAGTVAAL+NSIGVVGVAPSADLYAVKVLGANGRGSVSGIAQGLEWAAANNMHIA
Sbjct 61 GHGTHVAGTVAALDNSIGVVGVAPSADLYAVKVLGANGRGSVSGIAQGLEWAAANNMHIA 120
Query 121 NMSLGSDAPSSTLERAVNYATSRDVLVIAATGNNGSGSVGYPARYANAMAVGATDQNNRR 180
NMSLGSDAPSSTLERAVNYATSRDVLVIAATGNNGSGSVGYPARYANAMAVGATDQNNRR
Sbjct 121 NMSLGSDAPSSTLERAVNYATSRDVLVIAATGNNGSGSVGYPARYANAMAVGATDQNNRR 180
Query 181 ANFSQYGTGIDIVAPGVNVQSTYPGNRYVSMNGTSMATPHVAGAAALVKQRYPSWNATQI 240
ANFSQYGTGIDIVAPGVNVQSTYPGNRYVSMNGTSMATPHVAGAAALVKQRYPSWNATQI
Sbjct 181 ANFSQYGTGIDIVAPGVNVQSTYPGNRYVSMNGTSMATPHVAGAAALVKQRYPSWNATQI 240
Query 241 RNHLKNTATNLGNSSQFGSGLVNAEAATR 269
RNHLKNTATNLGNSSQFGSGLVNAEAATR
Sbjct 241 RNHLKNTATNLGNSSQFGSGLVNAEAATR 269
Claims 1, 8, 20-25 remain provisionally rejected and claims 10 and 32 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over (i) claims 1-14 of copending Application No. 18/720,046 (common inventors Babe, Goedegebuur, and Mulder), (ii) claims 1-14 of copending Application No. 17/613,224 (common inventors Babe, Goedegebuur, Mulder and Pricelius), and (iii) claims 1-7, 9-14 of copending Application No. 18/065, 644 (common inventors Babe, Goedegebuur, and Mulder; different assignee).
Applicant has requested the Office hold these rejections in abeyance until allowable subject matter is indicated.
Applicant’s arguments have been fully considered. In view of the fact that no arguments have been filed traversing the Examiner’s position and no terminal disclaimer has been filed, these rejections are maintained.
Claims 1, 10, 18, 20-25 and 32 of the instant application are directed in part to a (A) variant of the polypeptide of SEQ ID NO: 18 having at least 90% sequence identity to the polypeptide of SEQ ID NO: 18, wherein said variant has substitutions that correspond to substitutions S39E, N74D, and S99R in the polypeptide of SEQ ID NO: 85, (B) a detergent composition comprising the variant of (A), wherein said composition is a laundry detergent, a fabric softening composition, a dishwashing detergent, or a hard surface cleaning detergent, and (C) a composition comprising the variant of (A), wherein said composition comprises calcium, phosphate, boron, an enzyme stabilizer, and/or additional enzymes selected from alpha-amylases, beta-amylases, cellulases, cutinases, galactanases, laccases, lipases, mannases, oxidases, pectinases, peroxidases, proteases, xylanases, metalloproteases, and serine proteases, wherein the composition can be a granular composition, a powder, a solid, a bar, a liquid composition, a tablet, or a paste. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
Claims 1-14 of copending Application No. 18/720,046 are directed in part to a subtilisin variant of the polypeptide of SEQ ID NO: 1 having at least 80% sequence identity to the polypeptide of SEQ ID NO: 1, wherein said variant has substitutions that correspond to substitutions X039E and X099R in the polypeptide of SEQ ID NO: 1, or has substitutions that correspond to substitutions X039E, X099R, and X074D in the polypeptide of SEQ ID NO: 1, and compositions that comprise said variants and enzymes, including amylases, wherein said compositions are in the form of granules. SEQ ID NO: 1 of copending Application No. 18/720,046 is identical to SEQ ID NO: 85 of the instant application. The specification of copending Application No. 18/720,046 discloses compositions that comprise said variant, enzymes, detergents, bleaching agents, calcium, zinc, and enzyme stabilizers, wherein said compositions are boron-free or phosphate-free as preferred embodiments of the genus of compositions claimed. An alignment of the protein of SEQ ID NO: 18 and the variant of claims 1-14 of copending Application No. 18/720,046 (claim 3; S039E-N074D-S099R-F128G-D144G-R207Q-M211Q) shows this variant is 96% sequence identical to the polypeptide of SEQ ID NO: 18 of the instant application. See alignment below. Therefore, the variants and compositions of claims 1-14 of copending Application No. 18/720,046 either anticipate and/or render the variants and compositions of claims 1, 10, 18, 20-25 and 32 of the instant application obvious as written/interpreted in view of the preferred embodiments disclosed.
Query = SEQ ID NO:18
Sbjct = variant of SEQ ID NO:1 - copending application No. 18/720,046
NW Score Identities Positives Gaps
1330 257/269(96%) 263/269(97%) 0/269(0%)
Query 1 QQTVPWGITRVQAPAVHNRGITGSGVRVAILDSGISTHEDLNVRGGVSFVPGEPTTADLN 60
QQTVPWGITRVQAPAVHNRGITGSGVRVAILDSGIS HEDLN+RGG SFVPGEPTTADLN
Sbjct 1 QQTVPWGITRVQAPAVHNRGITGSGVRVAILDSGISAHEDLNIRGGASFVPGEPTTADLN 60
Query 61 GHGTHVAGTVAALNNSIGVVGVAPSADLYAVKVLGANGRGSVSGIAQGLEWAAANNMHIA 120
GHGTHVAGTVAAL+NSIGV+GVAP+A+LYAVKVLGANGRGSVSGIAQGLEWAA NNMHIA
Sbjct 61 GHGTHVAGTVAALDNSIGVIGVAPNAELYAVKVLGANGRGSVSGIAQGLEWAATNNMHIA 120
Query 121 NMSLGSDAPSSTLERAVNYATSRDVLVIAATGNNGSGSVGYPARYANAMAVGATDQNNRR 180
NMSLGSD PSSTLERAVNYATSR VLVIAATGNNGSGSVGYPARYANAMAVGATDQNNRR
Sbjct 121 NMSLGSDGPSSTLERAVNYATSRGVLVIAATGNNGSGSVGYPARYANAMAVGATDQNNRR 180
Query 181 ANFSQYGTGIDIVAPGVNVQSTYPGNRYVSMNGTSMATPHVAGAAALVKQRYPSWNATQI 240
ANFSQYGTGIDIVAPGVNVQSTYPGN+YVS NGTSMATPHVAGAAALVKQRYPSWNATQI
Sbjct 181 ANFSQYGTGIDIVAPGVNVQSTYPGNQYVSQNGTSMATPHVAGAAALVKQRYPSWNATQI 240
Query 241 RNHLKNTATNLGNSSQFGSGLVNAEAATR 269
RNHLKNTATNLGNSSQFGSGLVNAEAATR
Sbjct 241 RNHLKNTATNLGNSSQFGSGLVNAEAATR 269
Claims 1-14 of copending Application No. 17/613,224 are directed in part to a subtilisin variant of the polypeptide of SEQ ID NO: 1 having at least 80% sequence identity to the polypeptide of SEQ ID NO: 1, wherein said variant has substitutions that correspond to substitutions X039E, X099R, and X074D in the polypeptide of SEQ ID NO: 1, and compositions that comprise said variants and enzymes, including amylases, wherein said compositions are in the form of granules. SEQ ID NO: 1 of copending Application No. 17/613,224 is identical to SEQ ID NO: 85 of the instant application. The specification of copending Application No. 17/613,224 discloses compositions that comprise said variant, enzymes, detergents, bleaching agents, calcium, zinc, and enzyme stabilizers, wherein said compositions are boron-free or phosphate-free as preferred embodiments of the genus of compositions claimed. An alignment of the protein of SEQ ID NO: 18 and the variant of claims 1-14 of copending Application No. 17/613,224 (claim 3; S39E; S99R; D127E; N74D; M211Q, N212Q) shows this variant is 96% sequence identical to the polypeptide of SEQ ID NO: 18 of the instant application. See alignment below. Therefore, the variants and compositions of claims 1-14 of copending Application No. 17/613,224 either anticipate and/or render the variants and compositions of claims 1, 10, 18, 20-25 and 32 of the instant application obvious as written/interpreted in view of the preferred embodiments disclosed.
Query = SEQ ID NO:18
Sbjct = variant of SEQ ID NO:1 - copending application No. 17/613,224
NW Score Identities Positives Gaps
1329 257/269(96%) 263/269(97%) 0/269(0%)
Query 1 QQTVPWGITRVQAPAVHNRGITGSGVRVAILDSGISTHEDLNVRGGVSFVPGEPTTADLN 60
QQTVPWGITRVQAPAVHNRGITGSGVRVAILDSGIS HEDLN+RGG SFVPGEPTTADLN
Sbjct 1 QQTVPWGITRVQAPAVHNRGITGSGVRVAILDSGISAHEDLNIRGGASFVPGEPTTADLN 60
Query 61 GHGTHVAGTVAALNNSIGVVGVAPSADLYAVKVLGANGRGSVSGIAQGLEWAAANNMHIA 120
GHGTHVAGTVAAL+NSIGV+GVAP+A+LYAVKVLGANGRGSVSGIAQGLEWAA NNMHIA
Sbjct 61 GHGTHVAGTVAALDNSIGVIGVAPNAELYAVKVLGANGRGSVSGIAQGLEWAATNNMHIA 120
Query 121 NMSLGSDAPSSTLERAVNYATSRDVLVIAATGNNGSGSVGYPARYANAMAVGATDQNNRR 180
NMSLGS+ PSSTLERAVNYATSRDVLVIAATGNNGSGSVGYPARYANAMAVGATDQNNRR
Sbjct 121 NMSLGSEFPSSTLERAVNYATSRDVLVIAATGNNGSGSVGYPARYANAMAVGATDQNNRR 180
Query 181 ANFSQYGTGIDIVAPGVNVQSTYPGNRYVSMNGTSMATPHVAGAAALVKQRYPSWNATQI 240
ANFSQYGTGIDIVAPGVNVQSTYPGNRYVS GTSMATPHVAGAAALVKQRYPSWNATQI
Sbjct 181 ANFSQYGTGIDIVAPGVNVQSTYPGNRYVSQQGTSMATPHVAGAAALVKQRYPSWNATQI 240
Query 241 RNHLKNTATNLGNSSQFGSGLVNAEAATR 269
RNHLKNTATNLGNSSQFGSGLVNAEAATR
Sbjct 241 RNHLKNTATNLGNSSQFGSGLVNAEAATR 269
Claims 1-7, 9-14 of copending Application No. 18/065, 644 are directed in part to a fabric and home care composition comprising a surfactant and a protease, wherein protease is a subtilisin variant of the polypeptide of SEQ ID NO: 1 having at least 80% sequence identity to the polypeptide of SEQ ID NO: 1, wherein said variant has substitutions that correspond to substitutions X039E, X099R, and X074D in the polypeptide of SEQ ID NO: 1, wherein said composition comprises a bleaching system, and enzymes including amylases, SEQ ID NO: 1 of copending Application No. 18/065, 644 is identical to SEQ ID NO: 85 of the instant application. The specification of copending Application No. 18/065, 644 discloses compositions that comprise said variant, enzymes, detergents, bleaching agents, calcium, zinc, and enzyme stabilizers, wherein said compositions are boron-free or phosphate-free as preferred embodiments of the genus of compositions claimed. An alignment of the protein of SEQ ID NO: 18 and the variant of claims 1-7, 9-14 of copending Application No. 18/065, 644 shows this variant is 97% sequence identical to the polypeptide of SEQ ID NO: 18 of the instant application. See alignment below. Therefore, the variants and compositions of claims 1-7, 9-14 of copending Application No. 18/065, 644 either anticipate and/or render the variants and compositions of claims 1, 10, 18, 20-25 and 32 of the instant application obvious as written/interpreted in view of the preferred embodiments disclosed.
Query = SEQ ID NO:18
Sbjct = variant of SEQ ID NO:1 - copending application No. 18/065,644
NW Score Identities Positives Gaps
1344 260/269(97%) 265/269(98%) 0/269(0%)
Query 1 QQTVPWGITRVQAPAVHNRGITGSGVRVAILDSGISTHEDLNVRGGVSFVPGEPTTADLN 60
QQTVPWGITRVQAPAVHNRGITGSGVRVAILDSGIS HEDLN+RGG SFVPGEPTTADLN
Sbjct 1 QQTVPWGITRVQAPAVHNRGITGSGVRVAILDSGISAHEDLNIRGGASFVPGEPTTADLN 60
Query 61 GHGTHVAGTVAALNNSIGVVGVAPSADLYAVKVLGANGRGSVSGIAQGLEWAAANNMHIA 120
GHGTHVAGTVAAL+NSIGV+GVAP+A+LYAVKVLGANGRGSVSGIAQGLEWAA NNMHIA
Sbjct 61 GHGTHVAGTVAALDNSIGVIGVAPNAELYAVKVLGANGRGSVSGIAQGLEWAATNNMHIA 120
Query 121 NMSLGSDAPSSTLERAVNYATSRDVLVIAATGNNGSGSVGYPARYANAMAVGATDQNNRR 180
NMSLGSD PSSTLERAVNYATSRDVLVIAATGNNGSGSVGYPARYANAMAVGATDQNNRR
Sbjct 121 NMSLGSDFPSSTLERAVNYATSRDVLVIAATGNNGSGSVGYPARYANAMAVGATDQNNRR 180
Query 181 ANFSQYGTGIDIVAPGVNVQSTYPGNRYVSMNGTSMATPHVAGAAALVKQRYPSWNATQI 240
ANFSQYGTGIDIVAPGVNVQSTYPGNRYVSMNGTSMATPHVAGAAALVKQRYPSWNATQI
Sbjct 181 ANFSQYGTGIDIVAPGVNVQSTYPGNRYVSMNGTSMATPHVAGAAALVKQRYPSWNATQI 240
Query 241 RNHLKNTATNLGNSSQFGSGLVNAEAATR 269
RNHLKNTATNLGNSSQFGSGLVNAEAATR
Sbjct 241 RNHLKNTATNLGNSSQFGSGLVNAEAATR 269
These are provisional obviousness-type double patenting rejections because the conflicting claims have not in fact been patented.
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.
Conclusion
No claim is in condition for allowance.
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.
Applicant is advised that any Internet email communication by the Examiner has to be authorized by Applicant in written form. See MPEP § 502.03 (II). Without a written authorization by Applicant in place, the USPTO will not respond via Internet email to any Internet correspondence which contains information subject to the confidentiality requirement as set forth in 35 U.S.C. 122. Sample written authorization language can be found in MPEP § 502.03 (II). An Authorization for Internet Communications in a Patent Application or Request to Withdraw Authorization for Internet Communications form (SB/439) can be found at https://www.uspto.gov/patent/forms/ forms-patent-applications-filed-or-after-september-16-2012, which can be electronically filed.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to DELIA M RAMIREZ, Ph.D., whose telephone number is (571) 272-0938. The examiner can normally be reached on Monday-Friday from 8:30 AM to 5:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert B. Mondesi, can be reached at (408) 918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/DELIA M RAMIREZ/Primary Examiner, Art Unit 1652
DR
March 30, 2026