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 .
DETAILED ACTION
This application is a 371 of PCT/EP2021/073869.
The response filed on September 29, 2025 has been entered.
Election/Restrictions
Applicant's election with traverse of Group I with a species election of (1) SEQ ID NO:1 as the parent protease and (2) X215K/R/Q/N/T and at least three alterations selected from X3T, X4l, X9E, I35ID, X43R, X76D, X99D, X99F, X101E, X101L, X103A, X108T, X104I, X120D, X160S, X195E, X205I, X206L, X209W, X235L, X259D, X261W, and X262E in the reply filed on September 29, 2025 is acknowledged. The traversal is on the ground(s) that the identified Groups are related as product and process for the manufacture of the product (Groups I and III) and product and a process of use of said product (Groups I and IV). This is not found persuasive because the instant application is a national stage of a PCT application and Unity of Invention under PCT applies, not Restriction Practice. Therefore, section 806 of the MPEP does not apply in the instant national stage of 371 of PCT/EP2021/073869.
The requirement is still deemed proper and is therefore made FINAL.
Claims 6-19 and 24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on September 29, 2025.
A search and examination of protease variants having A215K and at least three amino acid substitutions selected from the group consisting of X3T, S3T, S9E, N43R, N76D, S99D, S101E, H120D, G195E, Q206L, Y209W, K235L, S259D, and L262E are disclosed in the prior art. See the rejections under 102 below. Therefore, examination has not been extended to a subsequent species.
Status of Claims
Claims 1-22 and 24 are pending.
Claims 16-19 and 24 are withdrawn.
Claims 1-15 and 20-22 are under examination.
Claim for Foreign Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on February 28, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 7, and 13-14 and claims 2-6, 8-12, 15 and 20-22 depending therefrom are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 1, 7, and 14, the phrase "e.g." renders the claims indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 2-6 and 9-11 and claims 7-8 depending therefrom are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 2-6 and 9-11 recite the phrase “preferable” and/or “most preferably”. The phrase renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 6 and claims 7-12 depending therefrom are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 6 recites the limitation “at least 4%, at least 10%... at least 500% or more”. The metes and bounds of the limitation in the context of the above claim is not clear. Use of a narrow numerical range that falls within a broader range in the same claim renders the claim indefinite because the boundaries of the claim are not discernible. Therefore, it is not clear whether the claimed narrower range is a limitation. Clarification is requested.
Claims 9 and 11 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 9 and 11 recite the limitation “10-30°C..15-25°C..20°C” and “15-20°C..20°C”, respectively. The metes and bounds of the limitation in the context of the above claim is not clear. Use of a narrow numerical range that falls within a broader range in the same claim renders the claim indefinite because the boundaries of the claim are not discernible. Therefore, it is not clear whether the claimed narrower range is a limitation. Clarification is requested.
Claims 10 and 11 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 10 and 11 recite the limitation “pH 3-9..pH 4-8..pH 4.5” and “pH 4-6.. pH 4-5”, respectively. The metes and bounds of the limitation in the context of the above claim is not clear. Use of a narrow numerical range that falls within a broader range in the same claim renders the claim indefinite because the boundaries of the claim are not discernible. Therefore, it is not clear whether the claimed narrower range is a limitation. Clarification is requested.
Claim 12 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.
Claim 12 recites the limitation "according to Example 1". The metes and bounds of the limitation in the context of the claims are not clear. Claims are to be complete in themselves. Incorporation by reference to a specific portion of the specification is permitted only in exceptional circumstances. See MPEP 2173.05(s).
Claims 13 and 15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “on par” in claims 13 and 15 is a relative term which renders the claim indefinite. The term “on par” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear as to how much protease activity is considered as “on par”. Clarification is requested.
Claim 13 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 13 recites the limitation “at least 100%, ..at least 101%.. at least 500% or more”. The metes and bounds of the limitation in the context of the above claim is not clear. Use of a narrow numerical range that falls within a broader range in the same claim renders the claim indefinite because the boundaries of the claim are not discernible. Therefore, it is not clear whether the claimed narrower range is a limitation. Clarification is requested.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 6-12 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.
MPEP 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow.'' In this case, the claims have been broadly interpreted to encompass any protease variants having at least 80% but less than 100% sequence identity to SEQ ID NO:1 and a X215K/R/Q/N/S/T amino acid substitution and at least three amino acid substitutions recited in claim 1 (amino acid position corresponding to SEQ ID NO:2), wherein the protease variant has an improved solubility of at least 4% to at least 500% or more compared to SEQ ID NO:1, has an improved solubility at 10-30°C, an improved solubility at a pH of 3-9, and has an improved solubility at 15-25°C and pH 4-6. Therefore, the claims are drawn to a genus of protease variants having at least 80% but less than 100% sequence identity and having the amino acid substitutions identified above, wherein the protease variant an improved solubility of at least 4% to at least 500% or more compared to SEQ ID NO:1, has an improved solubility at 10-30°C, an improved solubility at a pH of 3-9, and has an improved solubility at 15-25°C and pH 4-6.
MPEP 2163 I. states that to “satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention.
MPEP 2163. II.A.3.(a) sates that “Possession may be shown in many ways. For example, possession may be shown by describing an actual reduction to practice of the claimed invention. Possession may also be shown by a clear depiction of the invention in detailed drawings or in structural chemical formulas which permit a person skilled in the art to clearly recognize that inventor had possession of the claimed invention. An adequate written description of the invention may be shown by any description of sufficient, relevant, identifying characteristics so long as a person skilled in the art would recognize that the inventor had possession of the claimed invention.
According to MPEP 2163.II.A.3.(a).ii), “Satisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’"
The recitation of “improved solubility of at least 4% .. at least 500% or more” compared to SEQ ID NO:1, “improved solubility at 10-30°C”, “improved solubility at a pH of 3-9”, and “improved solubility at 15-25°C and pH 4-6” fails to provide a sufficient description of the genus of the protease variants as it merely describes the functional features of the genus without providing any definition of the structural features of the species within the genus. The specification does not specifically define any of the species that fall within the genus. The specification does not define any structural features commonly possessed by members of the genus that distinguish them from others. One skilled in the art therefore cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus.
Bacillus lentus protease was known in the art. Babe CN 109715791 – form PTO-892 and English Translation of CN 109715791. Retrieved on December 3, 2025 – form PTO-892) discloses a Bacillus lentus having 100% sequence identity to SEQ ID NO:1 of the instant application (Figure 1 and see the sequence alignment below). Although Babe discloses protease variants having improved protease activity and improved thermostability (2nd paragraph at page 89 of the English Translation), neither Babe, the prior art, nor the instant specification teach Bacillus lentus protease variants having at least 80% but less than 100% sequence identity to SEQ ID NO:1, a X215K/R/Q/N/S/T amino acid substitution, and at least three amino acid substitutions recited in claim 1, wherein the protease variants have improved solubility of at least 4% to at least 500% or more compared to SEQ ID NO:1, has an improved solubility at 10-30°C, an improved solubility at a pH of 3-9, and has an improved solubility at 15-25°C and pH 4-6.
The specification is limited to a protease variant of SEQ ID NO:1, wherein the variant consists of A215K/Q/N/T/S and wherein the protease variant has having improved solubility at 20°C and pH 4-5. While MPEP 2163 acknowledges that in certain situations “one species adequately supports a genus,” it also acknowledges that “[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.” In view of the widely variant species encompassed by the genus, the example disclosed above is not enough and does not constitute a representative number of species to describe the whole genus. Therefore, the specification fails to describe a representative species of the claimed genus.
Fransceus (J Ind Microbiol Biotechnol. 2017 May;44(4-5):687-695. –form PTO-892) reviews protein engineering techniques, such as random mutagenesis and recombination, directed evolution and iterative or combinatory saturation “hotspots”. Fransceus states that “a recurring problem, however, is choosing which amino acid positions should be targeted. Answering this question is not an easy feat and requires substantial insight in the relationship between an enzyme’s sequence or structure and its properties.” Sanavia (Computational and Structural Biotechnology Journal, Volume 18, 2020, Pages 1968-1979. –form PTO-892) discloses challenges in the prediction of protein stability in the occurrence of multiple mutations. “Multiple-point mutations are common variations of the protein sequence that may be needed in protein engineering when a single-point mutation is not enough to yield the desired stability change. Dealing with multiple-site variations adds another level of complexity beyond the prediction of the effect of a single variant on protein stability, since it requires the learning of many types of combinatorial effects”.
One of skill in the art could identify protease variants having at least 80% sequence identity to the protease of SEQ ID NO:1. However, there is no teaching regarding which 20% of the amino acids of SEQ ID NO:1, other than the amino acid at the position corresponding to 215 of SEQ ID NO:1, that can be modified and result in protease having improved solubility of at least 4% to at least 500% or more compared to SEQ ID NO:1, has an improved solubility at 10-30°C, an improved solubility at a pH of 3-9, and has an improved solubility at 15-25°C and pH 4-6 compared to the protease of SEQ ID NO:1.
An important consideration is that structure is not necessarily a reliable indicator of function. In the instant case, there is no disclosure relating similarity of structure to conservation of function. Conservation of structure is not necessarily a surrogate for conservation of function. Since the claimed invention is that of an enzyme, and there is no disclosure of the domains responsible for improved solubility of at least 4% to at least 500% or more compared to SEQ ID NO:1, has an improved solubility at 10-30°C, an improved solubility at a pH of 3-9, and has an improved solubility at 15-25°C and pH 4-6 compared to the protease of SEQ ID NO:1, the absence of information may be persuasive that those of skill in the art would not take the disclosure as generic.
Given this lack of description of the representative species encompassed by the genus of the claims, the specification fails to sufficiently describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize that applicants were in possession of the inventions of claims 6-12.
Claims 6-12 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 protease variant of SEQ ID NO:1, wherein the variant consists of A215K/Q/N/T/S and wherein the protease variant has having improved solubility at 20°C and pH 4-5, does not reasonably provide enablement any protease variant having at least 80% but less than 100% sequence identity and having the amino acid substitutions identified above, wherein the protease variant an improved solubility of at least 4% to at least 500% or more compared to SEQ ID NO:1, has an improved solubility at 10-30°C, an improved solubility at a pH of 3-9, and has an improved solubility at 15-25°C and pH 4-6. 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 use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
The breadth of the claims.
MPEP 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow.'' In this case, the claims have been broadly interpreted to encompass any protease variants having at least 80% but less than 100% sequence identity to SEQ ID NO:1 and a X215K/R/Q/N/S/T amino acid substitution and at least three amino acid substitutions recited in claim 1 (amino acid position corresponding to SEQ ID NO:2), wherein the protease variant has an improved solubility of at least 4% to at least 500% or more compared to SEQ ID NO:1, has an improved solubility at 10-30°C, an improved solubility at a pH of 3-9, and has an improved solubility at 15-25°C and pH 4-6. Therefore, the claims are drawn to any protease variant having at least 80% but less than 100% sequence identity and having the amino acid substitutions identified above, wherein the protease variant an improved solubility of at least 4% to at least 500% or more compared to SEQ ID NO:1, has an improved solubility at 10-30°C, an improved solubility at a pH of 3-9, and has an improved solubility at 15-25°C and pH 4-6.
The claims are not commensurate with the enablement provided by the disclosure with regard to the extremely large number of polypeptides having improved solubility of at least 4% to at least 500% or more compared to SEQ ID NO:1, has an improved solubility at 10-30°C, an improved solubility at a pH of 3-9, and has an improved solubility at 15-25°C and pH 4-6. In the instant case, the specification is limited to a protease variant of SEQ ID NO:1, wherein the variant consists of A215K/Q/N/T/S and wherein the protease variant has having improved solubility at 20°C and pH 4-5.
The quantity of experimentation required to practice the claimed invention based on the teachings of the specification.
While enzyme isolation techniques, recombinant and mutagenesis techniques were known in the art at the time of the invention, e.g. mutagenesis, and it is routine in the art to screen for variants comprising multiple substitutions or multiple modifications as encompassed by the instant claims, the specific amino acid positions within the protein's sequence where amino acid modifications can be made with a reasonable expectation of success in obtaining the desired activity/utility are limited in any protein and the result of such modifications is unpredictable. In addition, one skilled in the art would expect any tolerance to modification for a given protein to diminish with each further and additional modification, e.g. multiple substitutions.
In the absence of: (a) rational and predictable scheme for making proteases having improved solubility of at least 4% to at least 500% or more compared to SEQ ID NO:1, improved solubility at 10-30°C, improved solubility at a pH of 3-9, and improved solubility at 15-25°C and pH 4-6 and (b) a correlation between structure and the function of having improved solubility of at least 4% to at least 500% or more compared to SEQ ID NO:1, improved solubility at 10-30°C, improved solubility at a pH of 3-9, and improved solubility at 15-25°C and pH 4-6, the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful. One of skill in the art would have to test these infinite possible polypeptides to determine which proteases have improved solubility of at least 4% to at least 500% or more compared to SEQ ID NO:1, improved solubility at 10-30°C, improved solubility at a pH of 3-9, and improved solubility at 15-25°C and pH 4-6. While enablement is not precluded by the necessity for routine screening, if a large amount of screening is required, as is the case herein, the specification must provide a reasonable amount of guidance which respect to the direction in which the experimentation should proceed so that a reasonable number of species can be selected for testing. In view of the fact that such guidance has not been provided in the instant specification, it would require undue experimentation to enable the full scope of the claims.
The state of prior art, the relative skill of those in the art, and predictability or unpredictability of the art.
Since the amino acid sequence of the mutant determines its structural and functional properties, predictability of which changes can be tolerated in a protein's amino acid sequence and obtain the desired activity requires a knowledge of and guidance with regard to which amino acids in the protein's sequence, if any, are tolerant of modification and which are conserved (i.e. expectedly intolerant to modification), and detailed knowledge of the ways in which the proteins' structure relates to its function. In the instant case, neither the specification or the art provide a correlation between structure and activity such that one of skill in the art can envision the structure of any polypeptides having deoxyribose-phosphate aldolase activity or predict said function of a polypeptide from its primary structure. In addition, the art does not provide any teaching or guidance as to (1) which amino acids within the polypeptide of SEQ ID NO:1 other than A215 that can be modified and which ones are conserved such that one of skill in the art can make the recited protease variants having improved solubility of at least 4% to at least 500% or more compared to SEQ ID NO:1, improved solubility at 10-30°C, improved solubility at a pH of 3-9, and improved solubility at 15-25°C and pH 4-6, (2) which segments of the polypeptide of SEQ ID NO:1 that are essential for having improved solubility of at least 4% to at least 500% or more compared to SEQ ID NO:1, improved solubility at 10-30°C, improved solubility at a pH of 3-9, and improved solubility at 15-25°C and pH 4-6, and (3) the general tolerance of the polypeptide of SEQ ID NO:1 to structural modifications and the extent of such tolerance. The art clearly teaches that changes in a protein's amino acid sequence to obtain the desired activity without any guidance/knowledge as to which amino acids in a protein are required for that activity is highly unpredictable. At the time of the invention there was a high level of unpredictability associated with altering a polypeptide sequence with an expectation that the polypeptide will maintain the desired activity. For example, Studer (Residue mutations and their impact on protein structure and function: detecting beneficial and pathogenic changes. Biochem. J. (2013) 449, 581–594. – form PTO-892) teach that (1) protein engineers are frequently surprised by the range of effects caused by single mutations that they hoped would change only one specific and simple property in enzymes, (2) the often surprising results obtained by experiments where single mutations are made reveal how little is known about the rules of protein stability, and (3) the difficulties in designing de novo stable proteins with specific functions.
Bacillus lentus protease was known in the art. Babe CN 109715791 – form PTO-892 and English Translation of CN 109715791. Retrieved on December 3, 2025 – form PTO-892) discloses a Bacillus lentus having 100% sequence identity to SEQ ID NO:1 of the instant application (Figure 1 and see the sequence alignment below). Although Babe discloses protease variants having improved protease activity and improved thermostability (2nd paragraph at page 89 of the English Translation), neither Babe, the prior art, nor the instant specification teach Bacillus lentus protease variants having at least 80% but less than 100% sequence identity to SEQ ID NO:1, a X215K/R/Q/N/S/T amino acid substitution, and at least three amino acid substitutions recited in claim 1, wherein the protease variants have improved solubility of at least 4% to at least 500% or more compared to SEQ ID NO:1, has an improved solubility at 10-30°C, an improved solubility at a pH of 3-9, and has an improved solubility at 15-25°C and pH 4-6.
Fransceus (J Ind Microbiol Biotechnol. 2017 May;44(4-5):687-695. – form PTO-892) reviews protein engineering techniques, such as random mutagenesis and recombination, directed evolution and iterative or combinatory saturation “hotspots”. Fransceus states that “a recurring problem, however, is choosing which amino acid positions should be targeted. Answering this question is not an easy feat and requires substantial insight in the relationship between an enzyme’s sequence or structure and its properties.” Sanavia (Computational and Structural Biotechnology Journal, Volume 18, 2020, Pages 1968-1979. – form PTO-892) discloses challenges in the prediction of protein stability in the occurrence of multiple mutations. “Multiple-point mutations are common variations of the protein sequence that may be needed in protein engineering when a single-point mutation is not enough to yield the desired stability change. Dealing with multiple-site variations adds another level of complexity beyond the prediction of the effect of a single variant on protein stability, since it requires the learning of many types of combinatorial effects”.
The amount of direction or guidance presented and the existence of working examples.
The specification is limited to a protease variant of SEQ ID NO:1, wherein the variant consists of A215K/Q/N/T/S and wherein the protease variant has having improved solubility at 20°C and pH 4-5. However, the speciation fails to provide any information as to (1) specific substrates associated with any protease variants having at least 80% sequence identity to SEQ ID NO:1 and having improved solubility of at least 4% to at least 500% or more compared to SEQ ID NO:1, improved solubility at 10-30°C, improved solubility at a pH of 3-9, and improved solubility at 15-25°C and pH 4-6 or (2) structural elements required in a polypeptide having improved solubility of at least 4% to at least 500% or more compared to SEQ ID NO:1, improved solubility at 10-30°C, improved solubility at a pH of 3-9, and improved solubility at 15-25°C and pH 4-6. No correlation between structure and function of having improved solubility of at least 4% to at least 500% or more compared to SEQ ID NO:1, improved solubility at 10-30°C, improved solubility at a pH of 3-9, and improved solubility at 15-25°C and pH 4-6 has been presented.
Thus, in view of the overly broad scope of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability of the prior art in regard to structural changes and their effect on function and the lack of knowledge about a correlation between structure and function, an undue experimentation would be necessary one having ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of polypeptides having the desired biological characteristics recited in the claims are unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Claim Rejections - 35 USC § 102
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 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-4 and 13 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Masui (Rational design for stabilization and optimum pH shift of serine protease AprN. Journal of Fermentation and Bioengineering, Volume 85, Issue 1,1998, Pages 30-36 – form PTO-892).
MPEP 2113 states that “ [P]product by process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. [E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production.”. In the instant case, the structure of the claimed protease variant implied is the same whether the protease variant is obtained from any recombinant engineering of SEQ ID NO:1 or is obtained from any source (including wild type proteases), as long as the resulting product has the structural limitations recited in the claims (polypeptide having at least 80% but less than 100% sequence identity to SEQ ID NO:1 and having an X215X amino acid substitution and at least three further amino acid substitutions recited in the claim 1. Therefore, the claims have been broadly interpreted as a protease having at least 80% but less than 100% sequence identity to SEQ ID NO:1 and not having an Ala at the position corresponding to 215 of SEQ ID NO:2 and at least three other amino acid substitutions recited in claim 1.
Regarding claims 1-4, Masui disclose a Bacillus sp. B21-2 protease having 85.3% sequence identity to the protease of SEQ ID NO:1 of the instant application, wherein the protease has a serine residue at the position corresponding to 215 of SEQ ID NO:2, a threonine residue at the position corresponding to 3 of SEQ ID NO:2, an arginine residue at the position corresponding to 43 of SEQ ID NO:2, and an isoleucine residue at the position corresponding to 104 of SEQ ID NO:2, (see Figures 2-3 and the sequence alignment below).
Regarding claim 13, Masui also discloses a Bacillus sp. B21-2 protease variant having improved protease activity compared to Bacillus sp. B21-2 protease (page 34, left column and Table 3).
Therefore, the reference of Masui anticipates claims 1-4 and 13.
Claim(s) 1-4, 6-8, 13-15, and 20-22 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Babe (CN 109715791 – form PTO-892 and English Translation of CN 109715791. Retrieved on December 3, 2025 – form PTO-892. The English Translation of CN 109715791 is used for specific passages).
Babe discloses a Bacillus lentus protease of SEQ ID NO:1 which as 100% sequence identity to SEQ ID NO:1 of the instant application (Figure 1 of CN 109715791 and see the sequence alignment below). Babe discloses protease variants of SEQ ID NO:1, wherein the position numbers are based on the numbering of the Bacillus amyloliquefaciens protease of SEQ ID NO:2, which has 100% sequence identity to the protease of SEQ ID NO:2 of the instant application (Figure 1, top paragraph at page 8, and see the sequence alignment below).
Regarding claims 1-4, Babe discloses a protease variant of SEQ ID NO:1, wherein the variant has S3V, I8V, S24R, P40E, N76D, S78G/N, S87D/R, G118R, S128L/R, P129Q, S130, Q206L, Y209W, P210I, T213A, A215K, L217K, M222Q, H249R, and N261I amino acid substitutions (2nd paragraph under clause (iii) at page 9 and claim 14, clause (iii)). Since the protease variant of Babe has 20 amino acid substitutions, the protease variant of Babe has at least 80% sequence identity to SEQ ID NO:1 of the instant application.
Regarding claims 6-8, the protease variant of Babe has improved solubility, as evidenced by Lenhard (US 2023/0323330 – form PTO-892). Lenhard discloses that the X215K amino acid substitution in the protease of SEQ ID NO:1 (which has 100% sequence identity to the protease of SEQ ID NO:1 of the instant application, see the sequence alignment below) confers improved solubility and improves solubility by at least 100% to at least 500% compared to the parent protease of SEQ ID NO:1 (page 13, lines 14-16 and page 57 of the reference specification). MPEP 2112. II. states that “[t]here is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference.”.
Regarding claim 13, Babe discloses that the protease variants have improved protease activity compared to the parent protease (2nd paragraph at page 89).
Regarding claims 14-15, the parent protease of Babe is identical to the parent protease of SEQ ID NO:1 of the instant application and does not have the amino acid substitutions recited in claim 14 (Figure and see the sequence alignment below).
Regarding claims 20-22, Babe discloses a detergent composition in the form of a powder or liquid comprising the protease variants and one or more detergent components (2nd and 3rd paragraphs at page 94).
Therefore, the reference of Babe anticipates claims 1-4, 6-8, 13-15, and 20-22.
Claim(s) 1-4, 6-8, 13-15, and 20-22 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Knotzel (US 2022/0145220 – form PTO-892).
Knotzel discloses a Bacillus lentus protease of SEQ ID NO:1 which as 100% sequence identity to SEQ ID NO:1 of the instant application (Figure 1 and see the sequence alignment below). Knotzel discloses protease variants of SEQ ID NO:1, wherein the position numbers are based on the numbering of the Bacillus amyloliquefaciens protease of SEQ ID NO:2, which has 100% sequence identity to the protease of SEQ DI NO:2 of the instant application (Figure 2 and see the sequence alignment below).
Regarding claims 1-4, Knotzel disclose a protease variant of SEQ ID NO:1, wherein the variant has A215K amino acid substitution and one or more S9E, N43R, N76D, S99D, S101E, H120D, G195E, K235L, S259D, Y209W, and L262E amino acid substitutions ([0088]-[0089] and [0104]), A215K amino acid amino acid substitution and S9E+N43R+N76D+V205I+Q206L+Y209W+S259D+N261W+L262E ([0089] and [0096], and N62D+G97D+S101E+V1771+Y209W+A215K+L262E ([0110] and claims 7-8 and 17). Since the protease variant of Knotzel has up to 12 amino acid substitutions, the protease variant of Knotzel has at least 80% sequence identity to SEQ ID NO:1 of the instant application.
Regarding claim 5, Knotzel disclose a protease variant of SEQ ID NO:1, wherein the variant has A215K amino acid amino acid substitution and S9E+N43R+N76D+V205I+Q206L+Y209W+S259D+N261W+L262E ([0089] and [0096]).
Regarding claims 6-8, the protease variant of Knotzel has improved solubility, as evidenced by Lenhard (US 2023/0323330 – form PTO-892). Lenhard discloses that the X215K amino acid substitution in the protease of SEQ ID NO:1 (which has 100% sequence identity to the protease of SEQ ID NO:1 of the instant application, see the sequence alignment below) confers improved solubility and improves solubility by at least 100% to at least 500% compared to the parent protease of SEQ ID NO:1 (page 13, lines 14-16 and page 57 of the reference specification). MPEP 2112. II. states that “[t]here is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference.”.
Regarding claim 13, Knotzel discloses that the protease variants has improved washing performance and therefore, the protease variants have a protease activity that is on par with the protease activity of the parent protease of SEQ ID NO:1 ([0009] and [0016]).
Regarding claims 14-15, the parent protease of Knotzel is identical to the parent protease of SEQ ID NO:1 of the instant application and does not have the amino acid substitutions recited in claim 14 (Figures 1-2 and see the sequence alignment below).
Regarding claims 20-22, Knotzel discloses a detergent composition in the form of a gel or liquid comprising the protease variants and one or more detergent components ([0384]-[0385] and [0389] and claims 7-8 and 17).
Therefore, the reference of Knotzel anticipates claims 1-8, 13-15, and 20-22.
The applied reference has a common assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Claim Rejections - 35 USC § 103
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.
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.
Claims 20-22 are rejected under 35 U.S.C. 103 as being unpatentable over Masui (Rational design for stabilization and optimum pH shift of serine protease AprN. Journal of Fermentation and Bioengineering, Volume 85, Issue 1,1998, Pages 30-36 –form PTO-892) and Babe (CN 109715791 – form PTO-892 and English Translation of CN 109715791. Retrieved on December 3, 2025 – form PTO-892. The English Translation of CN 109715791 is used for specific passages).
MPEP 2113 states that “ [P]product by process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. [E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production.”. In the instant case, the structure of the claimed protease variant implied is the same whether the protease variant is obtained from any recombinant engineering of SEQ ID NO:1 or is obtained from any source (including wild type proteases), as long as the resulting product has the structural limitations recited in the claims (polypeptide having at least 80% but less than 100% sequence identity to SEQ ID NO:1 and having an X215X amino acid substitution and at least three further amino acid substitutions recited in the claim 1. Therefore, the claims have been broadly interpreted as a protease having at least 80% but less than 100% sequence identity to SEQ ID NO:1 and not having an Ala at the position corresponding to 215 of SEQ ID NO:2 and at least three other amino acid substitutions recited in claim 1.
Regarding claims 1-4, Masui disclose a Bacillus sp. B21-2 protease having 85.3% sequence identity to the protease of SEQ ID NO:1 of the instant application, wherein the protease has a serine residue at the position corresponding to 215 of SEQ ID NO:2, a threonine residue at the position corresponding to 3 of SEQ ID NO:2, an arginine residue at the position corresponding to 43 of SEQ ID NO:2, and an isoleucine residue at the position corresponding to 104 of SEQ ID NO:2, (see Figures 2-3 and the sequence alignment below).
Regarding claim 13, Masui discloses a Bacillus sp. B21-2 protease variant having improved protease activity compared to Bacillus sp. B21-2 protease (page 34, left column and Table 3).
Masui does not disclose a detergent composition comprising the protease.
Regarding claims 20-22, Babe discloses a detergent composition in the form of a powder or liquid comprising Bacillus protease variants of and one or more detergent components (2nd and 3rd paragraphs at page 94).
Therefore, in combining the teachings of Masui and Babe, it would have been obvious to one having ordinary skill in the art before the time the claimed invention was effectively filed to make a liquid or powder detergent composition comprising the protease variant of Masui and at least one detergent component. One of ordinary skill in the art would have been motivated to do so because use of a protease in a detergent composition was known in the art and the protease variant of Masui has improved protease activity compared to the parent protease. One of ordinary skill in the art would have had a reasonable expectation of success since Masui discloses a protease and Babe discloses a liquid or powder detergent comprising a protease and at least one detergent component. The rationale to support 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.
Therefore, the above references render claims 1-4, 13, and 20-22 prima facie obvious.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-4 and 20-22 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Claim interpretation
MPEP 2113 states that “ [P]product by process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. [E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production.”. In the instant case, the structure of the claimed protease variant implied is the same whether the protease variant is obtained from any recombinant engineering of SEQ ID NO:1 or is obtained from any source (including wild type proteases), as long as the resulting product has the structural limitations recited in the claims (polypeptide having at least 80% but less than 100% sequence identity to SEQ ID NO:1 and having an X215X amino acid substitution and at least three further amino acid substitutions recited in the claim 1. Therefore, the claims have been broadly interpreted as a protease having at least 80% but less than 100% sequence identity to SEQ ID NO:1 and not having an Ala at the position corresponding to 215 of SEQ ID NO:2 and at least three other amino acid substitutions recited in claim 1.
Regarding claims 1-4, Masui disclose a Bacillus sp. B21-2 protease having 85.3% sequence identity to the protease of SEQ ID NO:1 of the instant application, wherein the protease has a serine residue at the position corresponding to 215 of SEQ ID NO:2, a threonine residue at the position corresponding to 3 of SEQ ID NO:2, an arginine residue at the position corresponding to 43 of SEQ ID NO:2, and an isoleucine residue at the position corresponding to 104 of SEQ ID NO:2, (see Figures 2-3 and the sequence alignment below).
Regarding claims 20-22, the claims encompass a liquid composition comprising the protease variant and any other component, such as water.
Therefore, the claims read on a Bacillus sp. B21-2 protease and a liquid composition comprising said Bacillus sp. B21-2 protease.
Step 1: This part of the eligibility analysis evaluates whether the claim falls within any statutory category (see MPEP 2106.03). Since the claims are directed to a protease mutant, the claims are directed to a composition of matter, which is one of the statutory categories of invention. (Step 1: YES)
Step 2A Prong 1: This part of the eligibility analysis evaluates whether the claim recites a judicial exception (see MPEP 2106.04). The claimed protease variant and a generic liquid detergent composition comprising the protease variant and a generic component are not considered to have markedly different characteristics from what occurs in nature, Bacillus sp. B21-2 protease as discussed above and is considered to be a law of nature exception. Regarding claims 20-22, there is no indication in the specification that placing the protease in a generic liquid composition comprising water results in the protease having any characteristics (structural, functional, or otherwise) that are different from the naturally occurring Bacillus sp. B21-2 protease. Because there is no difference in characteristics (structural, functional, or otherwise) between the claimed protease and the naturally occurring Bacillus sp. B21-2 protease, the claimed protease and a composition comprising said protease are directed to a judicial exception.
Step 2A Prong 2: This part of the eligibility analysis evaluates whether the claim as a whole integrates the recited judicial exception into a practical application (see MPEP 2106.04(d)). This evaluation is performed by (a) identifying whether there are any additional recited elements in the claim beyond the judicial exception and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. Regarding claims 1-4, there are no additional elements recited in the claim beyond the judicial exception. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claimed protease is found naturally occurring in nature (Bacillus sp. B21-2 protease. Regarding claims 20-22, the claim recites a generic composition comprising the naturally occurring protease and naturally occurring water but does not recite any components of the composition other than the protease and generic component such as water (Step2 A: YES)
Step 2B: This part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim (see MPEP § 2106.05). The claims only recite the laws of nature and do not include any additional elements that could add significantly more to the judicial exceptions. (Step 2B: NO)
As such, the claims do not qualify as eligible subject matter.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4, 6-8, 13-15, and 20-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim claims 1, 4, 10-13, 15, and 18-25 of copending Application No. 17/435,555 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the instant application and the calims of the reference application are both directed to protease variants of SEQ ID NO:1. The protease of SEQ ID NO:1 of the instant application is identical to the protease of SEQ ID NO:1 of the reference application. The protease of SEQ ID NO:2 of the instant application is identical to the protease of SEQ ID NO:2 of the reference application.
Regarding claims 1-4 of the instant application, claim 1 of the reference application recites a detergent composition comprising a protease variant of SEQ ID NO:1, wherein the variant has N62D+G97D+S101E +V177I+ Y209W+A215K+L262E, N76D+G97D+N140D+S156D+ Y209W+A215K+L262E, N76D+G97D+S101E+T180A+Y209W+A215K+L262E, S9E+G97D+S101E+Y209W+A215K+L262E, S9E+N43R+N76D+S188E+Q191N+A194P+Q206L+Y209W+A215K+S259D+L262E, and S9R+K27M+N43R+N76D+V205I+Q206L+Y209W+A215K+Q245R+S259D+N261W+L262E. Since the protease variant of the reference application has 11 amino acid substitutions, the protease variant of the reference application has at least 80% sequence identity to SEQ ID NO:1 of the instant application. Therefore, claims 1-4 of the instant application are anticipated by claim 1 of the reference application.
Regarding claims 6-8 of the instant application, the protease variant of the reference application has improved solubility, as evidenced by Lenhard (US 2023/0323330 – form PTO-892). Lenhard discloses that the X215K amino acid substitution in the protease of SEQ ID NO:1 (which has 100% sequence identity to the protease of SEQ ID NO:1 of the instant application, see the sequence alignment below) confers improved solubility and improves solubility by at least 100% to at least 500% compared to the parent protease of SEQ ID NO:1 (page 13, lines 14-16 and page 57 of the reference specification). MPEP 2112. II. states that “[t]here is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference.”.
Regarding claim 13 of the instant application, claim 13 of the reference application recites that the protease variant has improved washing performance and therefore, the protease variant has a protease activity that is on par with the protease activity of the parent protease of SEQ ID NO:1 ([0009] and [0016]). Therefore, claim 13 of the instant application is anticipated by claim 1 of the reference application.
Regarding claims 14-15, of the instant application the parent protease of the reference application is identical to the parent protease of SEQ ID NO:1 of the instant application and does not have the amino acid substitutions recited in claim 14. Therefore, claims 14-15 of the instant application are anticipated by claim 1 of the reference application.
Regarding claims 20-22 of the instant application, claim 23 of the reference application recite a detergent composition having an improved wash performance comprising the protease variant of claim 1 and claim 25 recites that the detergent composition comprises one or more components. Therefore, claims 20-22 of the instant application is anticipated by claims 23 and 15 of the reference application.
Therefore, the conflicting claims are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-8 and 13-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim claims 1-19 and 21-22 of copending Application No. 18/043,515 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the instant application and the claims of the reference application are both directed to protease variants of SEQ ID NO:1. The protease of SEQ ID NO:1 of the instant application is identical to the protease of SEQ ID NO:1 of the reference application. The protease of SEQ ID NO:2 of the instant application is identical to the protease of SEQ ID NO:2 of the reference application.
Regarding claims 1-5 of the instant application, claim 1 and claim 5 of the reference application recites a protease variant of SEQ ID NO:1, wherein the variant has S9E, N43R, N76D, S99F, S101L, S103T, V104I, X127I, X194P, V205I, Q206L, Y209W, A215K, S259D, N261W, and L262E. Since the protease variant of the reference application has 16 amino acid substitutions, the protease variant of the reference application has at least 80% sequence identity to SEQ ID NO:1 of the instant application. Therefore, claims 1-5 of the instant application are anticipated by claims 1 and 5 of the reference application.
Regarding claims 6-8 of the instant application, the protease variant of the reference application has improved solubility by at least 100% to at least 500% compared to the parent protease of SEQ ID NO:1 (page 57 of the reference specification). The reference specification also discloses that the X215K amino acid substitution confers improved solubility (page 13, lines 14-16). Therefore, claims 6-8 of the instant application are anticipated by claim 1 of the reference application.
Regarding claim 13 of the instant application, claim 9 of the reference application recites that the protease variant has improved thermostability, which reads on improved protease activity at high temperatures. Therefore, claim 13 of the instant application is anticipated by claims 1, 5, and 9 of the reference application.
Regarding claims 14-15 of the instant application, the parent protease of the reference application is identical to the parent protease of SEQ ID NO:1 of the instant application and does not have the amino acid substitutions recited in claim 14. Therefore, claims 14-15 of the instant application are anticipated by claims 1, 5, and 9 of the reference application.
Therefore, the conflicting claims are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-8, 13-15, and 20-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim claims 1-19 and 21-22 of copending Application No. 18/043,515 (reference application) in view of Babe (CN 109715791 – form PTO-892 and English Translation of CN 109715791. Retrieved on December 3, 2025 – form PTO-892. The English Translation of CN 109715791 is used for specific passages). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the instant application and the claims of the reference application are both directed to protease variants of SEQ ID NO:1. The protease of SEQ ID NO:1 of the instant application is identical to the protease of SEQ ID NO:1 of the reference application. The protease of SEQ ID NO:2 of the instant application is identical to the protease of SEQ ID NO:2 of the reference application.
Regarding claims 1-5 of the instant application, claim 1 and claim 5 of the reference application recites a protease variant of SEQ ID NO:1, wherein the variant has S9E, N43R, N76D, S99F, S101L, S103T, V104I, X127I, X194P, V205I, Q206L, Y209W, A215K, S259D, N261W, and L262E. Since the protease variant of the reference application has 16 amino acid substitutions, the protease variant of the reference application has at least 80% sequence identity to SEQ ID NO:1 of the instant application. Therefore, claims 1-5 of the instant application are anticipated by claim 1 of the reference application.
Regarding claims 6-8 of the instant application, the protease variant of the reference application has improved solubility by at least 100% to at least 500% compared to the parent protease of SEQ ID NO:1 (page 57 of the reference specification). The reference specification also discloses that the X215K amino acid substitution confers improved solubility (page 13, lines 14-16). Therefore, claims 6-8 of the instant application are anticipated by claim 1 of the reference application.
Regarding claim 13 of the instant application, claim 9 of the reference application recites that the protease variant has improved thermostability, which reads on improved protease activity at high temperatures. Therefore, claim 13 of the instant application is anticipated by claims 1, 5, and 9 of the reference application.
Regarding claims 14-15 of the instant application, the parent protease of the reference application is identical to the parent protease of SEQ ID NO:1 of the instant application and does not have the amino acid substitutions recited in claim 14. Therefore, claims 14-15 of the instant application are anticipated by claims 1, 5, and 9 of the reference application.
The claims of the reference application do not recite a detergent composition comprising the protease variant.
Regarding claims 20-22, Babe discloses a detergent composition in the form of a powder or liquid comprising Bacillus protease variants of and one or more detergent components (2nd and 3rd paragraphs at page 94).
Therefore, it would have been obvious to one having ordinary skill to modify the claims of the reference application by making a liquid or powder detergent composition comprising the protease variant and at least one detergent component. One of ordinary skill in the art would have been motivated to do so because use of a protease in a detergent composition was known in the art and the protease variant of the reference claim has improved protease activity and improved solubility compared to the parent protease. One of ordinary skill in the art would have had a reasonable expectation of success since the claims of the reference application recites a protease and Babe discloses a liquid or powder detergent comprising a protease and at least one detergent component. The rationale to support 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.
Therefore, the conflicting claims are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-22 and 24 are pending.
Claims 16-19 and 24 are withdrawn.
Claims 1-15 and 20-22 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to YONG D PAK whose telephone number is (571)272-0935. The examiner can normally be reached M-Th: 5:30 am - 3:30 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Mondesi can be reached on 408-918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/YONG D PAK/Primary Examiner, Art Unit 1652
Sequence alignment between the protease of SEQ ID NO:1 of the instant application (“Qy”) and protease of Masui (“Db”)
O66153_BACSP
ID O66153_BACSP Unreviewed; 379 AA.
AC O66153;
DT 01-AUG-1998, integrated into UniProtKB/TrEMBL.
DT 01-AUG-1998, sequence version 1.
DT 05-FEB-2025, entry version 98.
DE SubName: Full=AprN {ECO:0000313|EMBL:BAA25184.1};
OS Bacillus sp.
OC Bacteria; Bacillati; Bacillota; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=1409 {ECO:0000313|EMBL:BAA25184.1};
RN [1] {ECO:0000313|EMBL:BAA25184.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=B21-2 {ECO:0000313|EMBL:BAA25184.1};
RA Masui A., Fujiwara N., Yamamoto K., Takagi M., Imanaka T.;
RT "Rational design for stabilization and optimum pH shift of serine protease
RT AprN.";
RL J. Ferment. Bioeng. 85:30-36(1998).
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000256|ARBA:ARBA00001913};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000256|ARBA:ARBA00004613}.
CC -!- SIMILARITY: Belongs to the peptidase S8 family.
CC {ECO:0000256|ARBA:ARBA00011073, ECO:0000256|PROSITE-ProRule:PRU01240,
CC ECO:0000256|RuleBase:RU003355}.
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DR EMBL; AB005792; BAA25184.1; -; Genomic_DNA.
DR AlphaFoldDB; O66153; -.
DR SMR; O66153; -.
DR MEROPS; S08.157; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd07477; Peptidases_S8_Subtilisin_subset; 1.
DR Gene3D; 3.30.70.80; Peptidase S8 propeptide/proteinase inhibitor I9; 1.
DR Gene3D; 3.40.50.200; Peptidase S8/S53 domain; 1.
DR InterPro; IPR000209; Peptidase_S8/S53_dom.
DR InterPro; IPR036852; Peptidase_S8/S53_dom_sf.
DR InterPro; IPR023827; Peptidase_S8_Asp-AS.
DR InterPro; IPR022398; Peptidase_S8_His-AS.
DR InterPro; IPR023828; Peptidase_S8_Ser-AS.
DR InterPro; IPR050131; Peptidase_S8_subtilisin-like.
DR InterPro; IPR015500; Peptidase_S8_subtilisin-rel.
DR InterPro; IPR010259; S8pro/Inhibitor_I9.
DR InterPro; IPR037045; S8pro/Inhibitor_I9_sf.
DR InterPro; IPR034202; Subtilisin_Carlsberg-like.
DR PANTHER; PTHR43806:SF11; CEREVISIN-RELATED; 1.
DR PANTHER; PTHR43806; PEPTIDASE S8; 1.
DR Pfam; PF05922; Inhibitor_I9; 1.
DR Pfam; PF00082; Peptidase_S8; 1.
DR PRINTS; PR00723; SUBTILISIN.
DR SUPFAM; SSF54897; Protease propeptides/inhibitors; 1.
DR SUPFAM; SSF52743; Subtilisin-like; 1.
DR PROSITE; PS51892; SUBTILASE; 1.
DR PROSITE; PS00136; SUBTILASE_ASP; 1.
DR PROSITE; PS00137; SUBTILASE_HIS; 1.
DR PROSITE; PS00138; SUBTILASE_SER; 1.
PE 3: Inferred from homology;
KW Calcium {ECO:0000256|ARBA:ARBA00022837};
KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|PROSITE-
KW ProRule:PRU01240};
KW Protease {ECO:0000256|ARBA:ARBA00022670, ECO:0000256|PROSITE-
KW ProRule:PRU01240}; Secreted {ECO:0000256|ARBA:ARBA00022525};
KW Serine protease {ECO:0000256|ARBA:ARBA00022825, ECO:0000256|PROSITE-
KW ProRule:PRU01240}; Signal {ECO:0000256|SAM:SignalP}.
FT SIGNAL 1..27
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 28..379
FT /evidence="ECO:0000256|SAM:SignalP"
FT /id="PRO_5004159498"
FT DOMAIN 34..110
FT /note="Inhibitor I9"
FT /evidence="ECO:0000259|Pfam:PF05922"
FT DOMAIN 133..370
FT /note="Peptidase S8/S53"
FT /evidence="ECO:0000259|Pfam:PF00082"
FT ACT_SITE 142
FT /note="Charge relay system"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01240"
FT ACT_SITE 172
FT /note="Charge relay system"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01240"
FT ACT_SITE 325
FT /note="Charge relay system"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU01240"
SQ SEQUENCE 379 AA; 38961 MW; EB6918B44172829D CRC64;
Query Match 85.3%; Score 1161; Length 379;
Best Local Similarity 82.8%;
Matches 222; Conservative 23; Mismatches 23; Indels 0; Gaps 0;
Qy 2 QSVPWGISRVQAPAAHNRGLTGSGVKVAVLDTGISTHPDLNIRGGASFVPGEPSTQDGNG 61
|:|||||:||||| | :|| ||:||:||||||||| | || ||||||||||||: ||||
Db 112 QTVPWGINRVQAPIAQSRGFTGTGVRVAVLDTGISNHADLRIRGGASFVPGEPNISDGNG 171
Qy 62 HGTHVAGTIAALNNSIGVLGVAPSAELYAVKVLGASGSGSVSSIAQGLEWAGNNGMHVAN 121
|||||||||||||||||||||||: :|| |||||||||||:| |||||:|| |||||:||
Db 172 HGTHVAGTIAALNNSIGVLGVAPNVDLYGVKVLGASGSGSISGIAQGLQWAANNGMHIAN 231
Qy 122 LSLGSPSPSATLEQAVNSATSRGVLVVAASGNSGAGSISYPARYANAMAVGATDQNNNRA 181
:|||| : |||:||||| ||: ||||||||||||||:: :||||||||||||||||||||
Db 232 MSLGSSAGSATMEQAVNQATASGVLVVAASGNSGAGNVGFPARYANAMAVGATDQNNNRA 291
Qy 182 SFSQYGAGLDIVAPGVNVQSTYPGSTYASLNGTSMATPHVAGAAALVKQKNPSWSNVQIR 241
|||||||||||||||| |||| ||: |:| |||||||||||| |||||||||||||||||
Db 292 SFSQYGAGLDIVAPGVGVQSTVPGNGYSSFNGTSMATPHVAGVAALVKQKNPSWSNVQIR 351
Qy 242 NHLKNTATSLGSTNLYGSGLVNAEAATR 269
||||||||:||:|| :||||||||||||
Db 352 NHLKNTATNLGNTNQFGSGLVNAEAATR 379
Sequence alignment between the protease of SEQ ID NO:2 of the instant application (“Qy”) and protease of Masui (“Db”)
Title: US-18-043-532-2
Perfect score: 1391
Sequence: 1 AQSVPYGVSQIKAPALHSQG..........KLGDSFYYGKGLINVQAAAQ 275
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 379 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 1 summaries
Database : AASEQ2_12032025_085931.pep:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 824 59.2 379 1 AASEQ2_12032025_085931
ALIGNMENTS
RESULT 1
AASEQ2_12032025_085931
Query Match 59.2%; Score 824; DB 1; Length 379;
Best Local Similarity 56.2%;
Matches 154; Conservative 54; Mismatches 60; Indels 6; Gaps 3;
Qy 2 QSVPYGVSQIKAPALHSQGYTGSNVKVAVIDSGIDSSHPDLKVAGGASMVPSETNPFQDN 61
|:||:|:::::|| |:|:||: |:|||:|:|| |:| ||:: |||| || | | |
Db 112 QTVPWGINRVQAPIAQSRGFTGTGVRVAVLDTGI-SNHADLRIRGGASFVPGEPN-ISDG 169
Qy 62 NSHGTHVAGTVAALNNSIGVLGVAPSASLYAVKVLGADGSGQYSWIINGIEWAIA NNMDV 121
| ||||||||:||||||||||||||: || |||||| ||| | | |::|| | | :
Db 170 NGHGTHVAGTIAALNNSIGVLGVAPNVDLYGVKVLGASGSGSISGIAQGLQWAANNGMHI 229
Qy 122 INMSLGGPSGSAALKAAVDKAVASGVVVVAAAGNEGTSGSSSTVGYPGKYPSVIAVGAVD 181
||||| :||| :: ||::| ||||:||||:|| | : ||:| :| : :|||| |
Db 230 ANMSLGSSAGSATMEQAVNQATASGVLVVAASGNSG----AGNVGFPARYANAMAVGATD 285
Qy 182 SSNQRASFSSVGPELDVMAPGVSIQSTLPGNKYGAYNGTSMASPHVAGAAALILSKHPNW 241
:| ||||| | ||::|||| :|||:||| | ::||||||:||||| |||: |:|:|
Db 286 QNNNRASFSQYGAGLDIVAPGVGVQSTVPGNGYSSFNGTSMATPHVAGVAALVKQKNPSW 345
Qy 242 TNTQVRSSLENTTTKLGDSFYYGKGLINVQAAAQ 275
:| |:|: |:|| | ||:: :| ||:| :|| :
Db 346 SNVQIRNHLKNTATNLGNTNQFGSGLVNAEAATR 379
Sequence alignment between the protease of SEQ ID NO:1 of the instant application (“Qy”) and protease of SEQ ID NO:2 of the instant application (“Db”)
Title: US-18-043-532-1
Perfect score: 1361
Sequence: 1 AQSVPWGISRVQAPAAHNRG..........SLGSTNLYGSGLVNAEAATR 269
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 275 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 1 summaries
Database : US-18-043-532-2.pep:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 851 62.5 275 1 US-18-043-532-2 Protease variants
ALIGNMENTS
RESULT 1
US-18-043-532-2
Query Match 62.5%; Score 851; DB 1; Length 275;
Best Local Similarity 60.0%;
Matches 165; Conservative 45; Mismatches 59; Indels 6; Gaps 3;
Qy 1 AQSVPWGISRVQAPAAHNRGLTGSGVKVAVLDTGI-STHPDLNIRGGASFVPGEPST-QD 58
|||||:|:|:::||| |::| ||| |||||:|:|| |:|||| : |||| || | : ||
Db 1 AQSVPYGVSQIKAPALHSQGYTGSNVKVAVIDSGIDSSHPDLKVAGGASMVPSETNPFQD 60
Qy 59 GNGHGTHVAGTIAALNNSIGVLGVAPSAELYAVKVLGASGSGSVSSIAQGLEWAGNNGMH 118
| ||||||||:|||||||||||||||| ||||||||| ||| | | |:||| | |
Db 61 NNSHGTHVAGTVAALNNSIGVLGVAPSASLYAVKVLGADGSGQYSWIINGIEWAIA NNMD 120
Qy 119 VANLSLGSPSPSATLEQAVNSATSRGVLVVAASGNSG----AGSISYPARYANAMAVGAT 174
| |:||| || || |: ||: | : ||:||||:|| | : :: || :| : :||||
Db 121 VINMSLGGPSGSAALKAAVDKAVASGVVVVAAAGNEGTSGSSSTVGYPGKYPSVIAVGAV 180
Qy 175 DQNNNRASFSQYGAGLDIVAPGVNVQSTYPGSTYASLNGTSMATPHVAGAAALVKQKNPS 234
| :| ||||| | ||::||||::||| ||: | : ||||||:|||||||||: |:|:
Db 181 DSSNQRASFSSVGPELDVMAPGVSIQSTLPGNKYGAYNGTSMASPHVAGAAALILSKHPN 240
Qy 235 WSNVQIRNHLKNTATSLGSTNLYGSGLVNAEAATR 269
|:| |:|: |:|| | || : || ||:| :|| :
Db 241 WTNTQVRSSLENTTTKLGDSFYYGKGLINVQAAAQ 275
Sequence alignment between the protease of SEQ ID NO:1 of the instant application (“Qy”) and the protease of SEQ ID NO:1 of Babe (“Db”)
Title: US-18-043-532-1
Perfect score: 1361
Sequence: 1 AQSVPWGISRVQAPAAHNRG..........SLGSTNLYGSGLVNAEAATR 269
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 269 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 1 summaries
Database : AASEQ2_12032025_115153.pep:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 1361 100.0 269 1 AASEQ2_12032025_115153
ALIGNMENTS
RESULT 1
AASEQ2_12032025_115153
Query Match 100.0%; Score 1361; DB 1; Length 269;
Best Local Similarity 100.0%;
Matches 269; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AQSVPWGISRVQAPAAHNRGLTGSGVKVAVLDTGISTHPDLNIRGGASFVPGEPSTQDGN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AQSVPWGISRVQAPAAHNRGLTGSGVKVAVLDTGISTHPDLNIRGGASFVPGEPSTQDGN 60
Qy 61 GHGTHVAGTIAALNNSIGVLGVAPSAELYAVKVLGASGSGSVSSIAQGLEWAGNNGMHVA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GHGTHVAGTIAALNNSIGVLGVAPSAELYAVKVLGASGSGSVSSIAQGLEWAGNNGMHVA 120
Qy 121 NLSLGSPSPSATLEQAVNSATSRGVLVVAASGNSGAGSISYPARYANAMAVGATDQNNNR 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 NLSLGSPSPSATLEQAVNSATSRGVLVVAASGNSGAGSISYPARYANAMAVGATDQNNNR 180
Qy 181 ASFSQYGAGLDIVAPGVNVQSTYPGSTYASLNGTSMATPHVAGAAALVKQKNPSWSNVQI 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 ASFSQYGAGLDIVAPGVNVQSTYPGSTYASLNGTSMATPHVAGAAALVKQKNPSWSNVQI 240
Qy 241 RNHLKNTATSLGSTNLYGSGLVNAEAATR 269
|||||||||||||||||||||||||||||
Db 241 RNHLKNTATSLGSTNLYGSGLVNAEAATR 269
Sequence alignment between the protease of SEQ ID NO:2 of the instant application (“Qy”) and the protease of SEQ ID NO:2 of Babe (“Db”)
Title: US-18-043-532-2
Perfect score: 1391
Sequence: 1 AQSVPYGVSQIKAPALHSQG..........KLGDSFYYGKGLINVQAAAQ 275
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 275 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 1 summaries
Database : AASEQ2_12032025_115533.pep:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 1384 99.5 275 1 AASEQ2_12032025_115533
ALIGNMENTS
RESULT 1
AASEQ2_12032025_115533
Query Match 99.5%; Score 1384; DB 1; Length 275;
Best Local Similarity 99.6%;
Matches 274; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 AQSVPYGVSQIKAPALHSQGYTGSNVKVAVIDSGIDSSHPDLKVAGGASMVPSETNPFQD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AQSVPYGVSQIKAPALHSQGYTGSNVKVAVIDSGIDSSHPDLKVAGGASMVPSETNPFQD 60
Qy 61 NNSHGTHVAGTVAALNNSIGVLGVAPSASLYAVKVLGADGSGQYSWIINGIEWAIA NNMD 120
|||||||||||||||||||||||||||||||||||||| |||||||||||||||||||||
Db 61 NNSHGTHVAGTVAALNNSIGVLGVAPSASLYAVKVLGAOGSGQYSWIINGIEWAIA NNMD 120
Qy 121 VINMSLGGPSGSAALKAAVDKAVASGVVVVAAAGNEGTSGSSSTVGYPGKYPSVIAVGAV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VINMSLGGPSGSAALKAAVDKAVASGVVVVAAAGNEGTSGSSSTVGYPGKYPSVIAVGAV 180
Qy 181 DSSNQRASFSSVGPELDVMAPGVSIQSTLPGNKYGAYNGTSMASPHVAGAAALILSKHPN 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 DSSNQRASFSSVGPELDVMAPGVSIQSTLPGNKYGAYNGTSMASPHVAGAAALILSKHPN 240
Qy 241 WTNTQVRSSLENTTTKLGDSFYYGKGLINVQAAAQ 275
|||||||||||||||||||||||||||||||||||
Db 241 WTNTQVRSSLENTTTKLGDSFYYGKGLINVQAAAQ 275
Sequence alignment between the protease of SEQ ID NO:1 of the instant application (“Qy”) and the protease of SEQ ID NO:1 of Knotzel (“Db”)
US-17-435-555-1
Filing date in PALM: 2021-09-01
Sequence 1, US/17435555
Publication No. US20220145220A1
GENERAL INFORMATION
APPLICANT: Novozymes A/S
TITLE OF INVENTION: DETERGENT COMPOSITIONS COMPRISING TWO PROTEASES
FILE REFERENCE: 14991-WO-PCT
CURRENT APPLICATION NUMBER: US/17/435,555
CURRENT FILING DATE: 2021-09-01
NUMBER OF SEQ ID NOS: 2
SEQ ID NO 1
LENGTH: 269
TYPE: PRT
ORGANISM: Bacillus lentus
Query Match 100.0%; Score 1361; Length 269;
Best Local Similarity 100.0%;
Matches 269; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AQSVPWGISRVQAPAAHNRGLTGSGVKVAVLDTGISTHPDLNIRGGASFVPGEPSTQDGN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AQSVPWGISRVQAPAAHNRGLTGSGVKVAVLDTGISTHPDLNIRGGASFVPGEPSTQDGN 60
Qy 61 GHGTHVAGTIAALNNSIGVLGVAPSAELYAVKVLGASGSGSVSSIAQGLEWAGNNGMHVA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GHGTHVAGTIAALNNSIGVLGVAPSAELYAVKVLGASGSGSVSSIAQGLEWAGNNGMHVA 120
Qy 121 NLSLGSPSPSATLEQAVNSATSRGVLVVAASGNSGAGSISYPARYANAMAVGATDQNNNR 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 NLSLGSPSPSATLEQAVNSATSRGVLVVAASGNSGAGSISYPARYANAMAVGATDQNNNR 180
Qy 181 ASFSQYGAGLDIVAPGVNVQSTYPGSTYASLNGTSMATPHVAGAAALVKQKNPSWSNVQI 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 ASFSQYGAGLDIVAPGVNVQSTYPGSTYASLNGTSMATPHVAGAAALVKQKNPSWSNVQI 240
Qy 241 RNHLKNTATSLGSTNLYGSGLVNAEAATR 269
|||||||||||||||||||||||||||||
Db 241 RNHLKNTATSLGSTNLYGSGLVNAEAATR 269
Sequence alignment between the protease of SEQ ID NO:2 of the instant application (“Qy”) and the protease of SEQ ID NO:2 of Knotzel (“Db”)
US-17-435-555-2
Filing date in PALM: 2021-09-01
Sequence 2, US/17435555
Publication No. US20220145220A1
GENERAL INFORMATION
APPLICANT: Novozymes A/S
TITLE OF INVENTION: DETERGENT COMPOSITIONS COMPRISING TWO PROTEASES
FILE REFERENCE: 14991-WO-PCT
CURRENT APPLICATION NUMBER: US/17/435,555
CURRENT FILING DATE: 2021-09-01
NUMBER OF SEQ ID NOS: 2
SEQ ID NO 2
LENGTH: 275
TYPE: PRT
ORGANISM: Bacillus amyloliquefaciens
Query Match 100.0%; Score 1391; Length 275;
Best Local Similarity 100.0%;
Matches 275; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AQSVPYGVSQIKAPALHSQGYTGSNVKVAVIDSGIDSSHPDLKVAGGASMVPSETNPFQD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AQSVPYGVSQIKAPALHSQGYTGSNVKVAVIDSGIDSSHPDLKVAGGASMVPSETNPFQD 60
Qy 61 NNSHGTHVAGTVAALNNSIGVLGVAPSASLYAVKVLGADGSGQYSWIINGIEWAIA NNMD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NNSHGTHVAGTVAALNNSIGVLGVAPSASLYAVKVLGADGSGQYSWIINGIEWAIA NNMD 120
Qy 121 VINMSLGGPSGSAALKAAVDKAVASGVVVVAAAGNEGTSGSSSTVGYPGKYPSVIAVGAV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VINMSLGGPSGSAALKAAVDKAVASGVVVVAAAGNEGTSGSSSTVGYPGKYPSVIAVGAV 180
Qy 181 DSSNQRASFSSVGPELDVMAPGVSIQSTLPGNKYGAYNGTSMASPHVAGAAALILSKHPN 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 DSSNQRASFSSVGPELDVMAPGVSIQSTLPGNKYGAYNGTSMASPHVAGAAALILSKHPN 240
Qy 241 WTNTQVRSSLENTTTKLGDSFYYGKGLINVQAAAQ 275
|||||||||||||||||||||||||||||||||||
Db 241 WTNTQVRSSLENTTTKLGDSFYYGKGLINVQAAAQ 275
Sequence alignment between the protease of SEQ ID NO:1 of the instant application (“Qy”) and the protease of SEQ ID NO:1 of Lenhard (“Db”)
US-18-043-515-1
Filing date in PALM: 2023-02-28
Sequence 1, US/18043515
Publication No. US20230323330A1
GENERAL INFORMATION
APPLICANT: Novozymes A/S
TITLE OF INVENTION: Polyester degrading protease variants
FILE REFERENCE: 15178-WO-PCT
CURRENT APPLICATION NUMBER: US/18/043,515
CURRENT FILING DATE: 2023-02-28
NUMBER OF SEQ ID NOS: 91
SEQ ID NO 1
LENGTH: 269
TYPE: PRT
ORGANISM: Bacillus clausii
Query Match 100.0%; Score 1361; Length 269;
Best Local Similarity 100.0%;
Matches 269; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AQSVPWGISRVQAPAAHNRGLTGSGVKVAVLDTGISTHPDLNIRGGASFVPGEPSTQDGN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AQSVPWGISRVQAPAAHNRGLTGSGVKVAVLDTGISTHPDLNIRGGASFVPGEPSTQDGN 60
Qy 61 GHGTHVAGTIAALNNSIGVLGVAPSAELYAVKVLGASGSGSVSSIAQGLEWAGNNGMHVA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GHGTHVAGTIAALNNSIGVLGVAPSAELYAVKVLGASGSGSVSSIAQGLEWAGNNGMHVA 120
Qy 121 NLSLGSPSPSATLEQAVNSATSRGVLVVAASGNSGAGSISYPARYANAMAVGATDQNNNR 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 NLSLGSPSPSATLEQAVNSATSRGVLVVAASGNSGAGSISYPARYANAMAVGATDQNNNR 180
Qy 181 ASFSQYGAGLDIVAPGVNVQSTYPGSTYASLNGTSMATPHVAGAAALVKQKNPSWSNVQI 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 ASFSQYGAGLDIVAPGVNVQSTYPGSTYASLNGTSMATPHVAGAAALVKQKNPSWSNVQI 240
Qy 241 RNHLKNTATSLGSTNLYGSGLVNAEAATR 269
|||||||||||||||||||||||||||||
Db 241 RNHLKNTATSLGSTNLYGSGLVNAEAATR 269
Prosecution Insights