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/JP2021/036956.
The amendment filed on November 13, 2025 has been entered.
Election/Restrictions
Applicant's election with traverse of Group I with a species election of X116H as the amino acid modification in the reply filed on November 13, 2025 is acknowledged. The traversal is on the ground(s) that for restriction to be proper, there must be a patentable difference between the species as claimed, MPEP 808.01(a), the burden is on the Office to provide reasons and/or examples to support any conclusion in regard to patentable distinction, MPEP 803, and the Office has not provided any reasons or examples to support a conclusion that the species are indeed patently distinct and MPEP 803. This is not found persuasive because MPEP 1893(d) states that “unity of invention analysis (not an independent and distinct analysis) is applicable in national stage applications submitted under 35 U.S.C. 371”. MPEP 808.01(a) and MPEP 803 do not apply to national stage applications submitted under 35 U.S.C. 371.
The traversal is on the ground(s) that the Office has the burden of explaining why each group lacks unity with either each other group specifically describing special features in each group. Applicant argues that unity of invention exists among Groups I-III because there is technical relationship that involves the same special technical feature. This is not found persuasive. The Requirement for Restriction/Election (lack of unity) mailed on September 30, 2025 discussed why Groups I-III and species lack unity of invention, see page 5. The technical feature linking Groups I-III and the species does not constitute a special technical feature as defined by PCT Rule 13.2, as it does not define a contribution over the prior art.
The traversal is on the ground(s) that since the International Search Authority searched all of the claims together, search of all the claims would not impose a serious burden. This is not found persuasive. MPEP 1893.03(e)II states that the international preliminary examination report “reflects the IPEA' s non-binding opinion regarding lack of unity of invention, novelty, inventive step and industrial applicability”.
Applicants request for rejoinder has been noted.
The requirement is still deemed proper and is therefore made FINAL.
Claims 2-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species (claim 2) and invention (claims 3-9), there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on November 13, 2025.
Status of Claims
Claims 1-9 are pending.
Claims 2-9 are withdrawn.
Claims 1 is under examination.
Claim for Foreign Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d).
Information Disclosure Statement
The information disclosure statement (IDS) submitted on October 2, 2024 and April 26, 2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification/Abstract
The abstract of the disclosure is objected to because the abstract has 274 words in length. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
Claim Rejections - 35 USC § 112
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.
Claim 1 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 1 recites the limitation “polypeptide consisting of the amino acid sequence of SEQ ID NO:2.., the polypeptide having any modification selected from….”. The metes and bounds of the limitation in the context of the claim are not clear. It is unclear how a polypeptide can consists of the amino acid sequence of SEQ ID NO:2 and also have amino acid modifications. A polypeptide either has the amino acid sequence of a given sequence identifier or it does not. Clarification is requested.
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.
Claim 1 is 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.'' Regarding claim 1, “polypeptide consisting of the amino acid sequence of SEQ ID NO:2.., the polypeptide having any modification selected from….” is indefinite, see the 112(b) rejection above. Therefore, the claim 1 has been broadly interpreted to encompass a mutant of the polypeptide of SEQ ID NO:2, wherein the polypeptide comprises a X116H amino acid modification and comprises any other amino acid modifications and wherein the polypeptide has glycine-glycine bond-degrading activity. Thus, the claims are directed to a genus of polypeptides having unknown structure except having a His residue at the position corresponding to 116 of SEQ ID NO:2, but having the function of glycine-glycine bond-degrading activity.
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 “glycine-glycine bond-degrading activity” fails to provide a sufficient description of the genus of the polypeptides 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.
Achromobacter lyticus β-lytic protease was known in the prior art. Li (Molecular cloning and nucleotide sequence of the beta-lytic protease gene from Achromobacter lyticus. J Bacteriol. 1990 Nov;172(11):6506-11 – form PTO-892) discloses a Achromobacter lyticus β-lytic protease having 100% sequence identity to the polypeptide having the amino acid sequence of SEQ ID NO:2 of the instant application. Achromobacter lyticus β-lytic protease is a M23 protease and has the function of glycine-glycine bond-degrading activity, see Hioki (WO2019/142773 – form PTO-1449 and the English Translation of WO 2019/142773 (cited previously on form PTO-892). However, neither the art nor the instant specification, other those corresponding to 116H, 170S, 172W, 173F, 174T, 178H and Δ179 of SEQ ID NO:2, disclose amino acid modifications that can be made in the polypeptide of SEQ ID NO:2 resulting in a polypeptide having glycine-glycine bond-degrading activity.
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 specification is limited to description of specific mutants of SEQ ID NO:2, wherein the mutant consists of 116H, 170S, 172W, 173F, 174T, 178H and/or Δ179 of SEQ ID NO:2 and the mutant has glycine-glycine bond-degrading activity. 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 examples above are 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.
Further, one of skill in the art could identify mutants of SEQ ID NO:2. However, there is no teaching regarding which amino acids, other than 116H, 170S, 172W, 173F, 174T, 178H and/or 179, can vary from SEQ ID NO:2 and result in polypeptide having glycine-glycine bond-degrading activity. 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.
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 claim 1.
Claim 1 is 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 specific mutants of SEQ ID NO:2, wherein the mutant consists of 116H, 170S, 172W, 173F, 174T, 178H and/or Δ179 of SEQ ID NO:2 and the mutant has glycine-glycine bond-degrading activity, does not reasonably provide enablement for any polypeptide having unknown structure except having a His residue at the position corresponding to 116 of SEQ ID NO:2, but having the function of glycine-glycine bond-degrading activity. 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.'' Regarding claim 1, “polypeptide consisting of the amino acid sequence of SEQ ID NO:2.., the polypeptide having any modification selected from….” is indefinite, see the 112(b) rejection above. Therefore, the claim 1 has been broadly interpreted to encompass a mutant of the polypeptide of SEQ ID NO:2, wherein the polypeptide comprises a X116H amino acid modification and comprises any other amino acid modifications and wherein the polypeptide has glycine-glycine bond-degrading activity. Thus, the claims are directed to any polypeptide having unknown structure except having a His residue at the position corresponding to 116 of SEQ ID NO:2, but having the function of glycine-glycine bond-degrading activity.
The claims are not commensurate with the enablement provided by the disclosure with regard to the extremely large number of polypeptides encompassed by the claim. In the instant case, the specification is limited to specific mutants of SEQ ID NO:2, wherein the mutant consists of 116H, 170S, 172W, 173F, 174T, 178H and/or Δ179 of SEQ ID NO:2 and the mutant has glycine-glycine bond-degrading activity.
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 any mutant of SEQ ID NO:2 having glycine-glycine bond-degrading activity, and (b) a correlation between structure and the function of having glycine-glycine bond-degrading activity, 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 polypeptides have glycine-glycine bond-degrading activity. 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 mutant of SEQ ID NO:2 and having glycine-glycine bond-degrading activity. In addition, the art does not provide any teaching or guidance as to (1) which segments of the polypeptide of SEQ ID NO:2 that are essential for polypeptides having glycine-glycine bond-degrading activity, and (2) the general tolerance of the polypeptide of SEQ ID NO:2 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.
Achromobacter lyticus β-lytic protease was known in the prior art. Li (Molecular cloning and nucleotide sequence of the beta-lytic protease gene from Achromobacter lyticus. J Bacteriol. 1990 Nov;172(11):6506-11 – form PTO-892) discloses a Achromobacter lyticus β-lytic protease having 100% sequence identity to the polypeptide having the amino acid sequence of SEQ ID NO:2 of the instant application. Achromobacter lyticus β-lytic protease is a M23 protease and has the function of glycine-glycine bond-degrading activity, see Hioki (WO2019/142773 – form PTO1449 and the English Translation of WO 2019/142773. Retreived on September 25, 2025 – cited previously on form PTO-892). However, neither the art nor the instant specification, other those corresponding to 116H, 170S, 172W, 173F, 174T, 178H and Δ179 of SEQ ID NO:2, disclose amino acid modifications that can be made in the polypeptide of SEQ ID NO:2 resulting in a polypeptide having glycine-glycine bond-degrading activity.
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 specific mutants of SEQ ID NO:2, wherein the mutant consists of 116H, 170S, 172W, 173F, 174T, 178H and/or Δ179 of SEQ ID NO:2 and the mutant has glycine-glycine bond-degrading activity. However, the speciation fails to provide any information as to (1) specific substrates associated with mutant of SEQ ID NO:2 and having glycine-glycine bond-degrading activity or (2) structural elements required in a polypeptide having glycine-glycine bond-degrading activity.
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 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by A0A2U9TAQ8_9GAMM (UniProtKB Database. September 12, 2018 - form PTO-892).
MPEP 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow.''. The limitation “polypeptide consisting of the amino acid sequence of SEQ ID NO:2.., the polypeptide having any modification selected from….” is indefinite, see the 112(b) rejection above. Therefore, the claim 1 has been broadly interpreted to encompass a mutant of the polypeptide of SEQ ID NO:2, wherein the polypeptide comprises a X116H amino acid modification and comprises any other amino acid modifications, wherein the polypeptide has glycine-glycine bond-degrading activity. Further, MPEP 2113 states that the “patentability of a product does not depend on its method of production.”. In the instant case, the structure of the claimed polypeptide implied is the same whether the polypeptide is obtained from recombinant engineering of SEQ ID NO:2 or is obtained from any source (including wild type proteins), as long as the resulting product has the structural limitations recited in the claims, having a His residue at the position corresponding to 116 of SEQ ID NO:2. Therefore, the claim has been broadly interpreted as a polypeptide having a His residue at the position corresponding to 116 of SEQ ID NO:2 and any other amino acid difference compared to SEQ ID NO:2 and having glycine-glycine bond-degrading activity.
Regarding claim 1, A0A2U9TAQ8_9GAMM discloses a Marilutibacter maris polypeptide which has a His residue at the position corresponding to 116 of SEQ ID NO:2 of the instant application (pages 1-2 and see the sequence alignment below). The Marilutibacter maris polypeptide of A0A2U9TAQ8_9GAMM is a β-lytic metalloprotease and belongs to M23 proteases. β-lytic metalloproteases belonging to M23 family of proteases have glycine-glycine bond-degrading activity, as evidenced by Rawlings (Evolutionary Families of Metalloproteases. Methods in Enzymology, Volume 248, pages 183-228, 1995. – form PTO-892, see page 224) and Hioki (WO2019/142773 – form PTO1449 and the English Translation of WO 2019/142773 – cited previously on form PTO-892, see last full paragraph at page 1).
Therefore, the reference of A0A2U9TAQ8_9GAMM anticipates claim 1.
Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) and/or 102(a)(2) as being anticipated by Hioki (102(a)(2): US 11,371,034 - form PTO-892 and 102(a)(1) and 102(a)(2): WO 2019/142773 – form PTO-1449. US 11,371,034 is used for specific passages of Hioki).
MPEP 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow.''. MPEP 2113 states that the “patentability of a product does not depend on its method of production.”. In the instant case, the structure of the claimed polypeptide implied is the same whether the polypeptide is obtained from recombinant engineering of SEQ ID NO:2 or is obtained from any source (including wild type proteins), as long as the resulting product has the structural limitations recited in the claims, having a Ser, Trp, and His residue at the positions corresponding to 170, 172, and 174, respectively, of SEQ ID NO:2 and an amino acid deletion corresponding to position 179 of SEQ ID NO:2. Therefore, the claim has been broadly interpreted as a polypeptide having a Ser, Trp, and His residue at the positions corresponding to 170, 172, and 174, respectively, of SEQ ID NO:2 of the instant application, having an amino acid deletion corresponding to position 179 of SEQ ID NO:2 of the instant application, and having glycine-glycine bond-degrading activity.
Regarding claim 1, Hioki discloses a Lysobacter gummosus M23 protease having the amino acid sequence of SEQ ID NO:10 and having glycine-glycine bond-degrading activity (Column 5, lines 1-12 and claim 2). The M23 protease of Hioki has at least 80% sequence identity to the polypeptide of SEQ ID NO:2 of the instant application, has a Ser, Trp, and His residue at the positions corresponding to 170, 172, and 174, respectively, of SEQ ID NO:2 of the instant application, and an amino acid deletion corresponding to position 179 of SEQ ID NO:2 of the instant application (see the sequence alignment below).
Therefore, the reference of Hioki anticipates claim 1.
The applied reference has a common inventors and 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 § 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.
Claim 1 is 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 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow.''. MPEP 2113 states that the “patentability of a product does not depend on its method of production.”. In the instant case, the structure of the claimed polypeptide implied is the same whether the polypeptide is obtained from recombinant engineering of SEQ ID NO:2 or is obtained from any source (including wild type proteins), as long as the resulting product has the structural limitations recited in the claims, having a Ser, Trp, and His residue at the positions corresponding to 170, 172, and/or 174, respectively, of SEQ ID NO:2 and/or an amino acid deletion corresponding to position 179 of SEQ ID NO:2. Therefore, the claim has been broadly interpreted as a polypeptide having a Ser, Trp, and His residue at the positions corresponding to 170, 172, and/or 174 of SEQ ID NO:2 of the instant application and/or an amino acid deletion corresponding to position 179 of SEQ ID NO:2 of the instant application and having glycine-glycine bond-degrading activity.
A0A2U9TAQ8_9GAMM discloses a Marilutibacter maris polypeptide which has a His residue at the position corresponding to 116 of SEQ ID NO:2 (pages 1-2 and see the sequence alignment below). The Marilutibacter maris polypeptide of A0A2U9TAQ8_9GAMM is a β-lytic metalloprotease that belongs to M23 proteases. β-lytic metalloproteases belonging to M23 family of proteases have glycine-glycine bond-degrading activity, as evidenced by Rawlings (Evolutionary Families of Metalloproteases. Methods in Enzymology, Volume 248, pages 183-228, 1995. – form PTO-892, see page 224) and Hioki (WO2019/142773 – form PTO1449 and the English Translation of WO 2019/142773– cited previously on form PTO-892, see last full paragraph at page 1).
Also, Hioki discloses a Lysobacter gummosus M23 protease having the amino acid sequence of SEQ ID NO:10 and having glycine-glycine bond-degrading activity (Column 5, lines 1-12 and claim 2). The M23 protease of Hioki has at least 80% sequence identity to the polypeptide of SEQ ID NO:2 of the instant application and has a Ser, Trp, and His residue at the positions corresponding to 170, 172, and 174, respectveily, of SEQ ID NO:2 of the instant application and an amino acid deletion corresponding to position 179 of SEQ ID NO:2 of the instant application (see the sequence alignment below).
Therefore, claim 1 is directed to naturally occurring products, Marilutibacter maris M23 protease and Lysobacter gummosus M23 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, 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 proteases are not considered to have markedly different characteristics from what occurs in nature, Marilutibacter maris M23 protease or Lysobacter gummosus M23 protease, as discussed above, and is considered to be a law of nature exception. Because there is no difference in characteristics (structural, functional, or otherwise) between the claimed protease and the naturally occurring Bacillus sp. protease, the claimed protease and detergent 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. 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 (Marilutibacter maris and Lysobacter gummosus). (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 claim only recites 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.
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 11,371,034 (reference patent).
Although the claims at issue are not identical, they are not patentably distinct from each other because they are claiming common subject matter, as follows:
MPEP 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow.''. MPEP 2113 states that the “patentability of a product does not depend on its method of production.”. In the instant case, the structure of the claimed polypeptide implied is the same whether the polypeptide is obtained from recombinant engineering of SEQ ID NO:2 or is obtained from any source (including wild type proteins), as long as the resulting product has the structural limitations recited in the claims, having a Ser, Trp, and His residue at the positions corresponding to 170, 172, and 174, respectively, of SEQ ID NO:2 and an amino acid deletion corresponding to position 179 of SEQ ID NO:2. Therefore, the claim has been broadly interpreted as a polypeptide having a Ser, Trp, and His residue at the positions corresponding to 170, 172, and 174 of SEQ ID NO:2 of the instant application, having an amino acid deletion corresponding to position 179 of SEQ ID NO:2 of the instant application, and having glycine-glycine bond-degrading activity.
Regarding claim 1 of the instant application, claims 1-2 of the reference patent recites an M23 protease having the amino acid sequence of SEQ ID NO:10 and having glycine-glycine bond-degrading activity. The M23 protease of the reference patent has at least 80% sequence identity to the polypeptide of SEQ ID NO:2 of the instant application, has a Ser, Trp, and His residue at the positions corresponding to 170, 172, and 174, respectively, of SEQ ID NO:2 of the instant application, and an amino acid deletion corresponding to position 179.
Therefore, the conflicting claims are not patentably distinct from each other.
Other Relevant Art
Hioki (Heterologous production of active form of beta-lytic protease by Bacillus subtilis and improvement of staphylolytic activity by protein engineering. Microb Cell Fact. 2021 Dec 28;20(1):231 – form PTO-892) discloses a mutant of Achromobacter lyticus β-lytic protease belonging to M23 protease family having 100% sequence identity SEQ ID NO:2 of the instant application, wherein the the mutant consists of Q116H/X amino acid modification and has glycine-glycine bond-degrading activity (abstract, 3rd full paragraph at page 3, Fig. 3, and Fig. 6). However, Hioki is not available as prior art because the reference was published or made known to the public after the instant invention was filed.
Conclusion
Claims 1-9 are pending.
Claims 2-9 are withdrawn.
Claim 1 is 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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, 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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/YONG D PAK/Primary Examiner, Art Unit 1652
Sequence alignment between the polypeptide of SEQ ID NO:2 of the instant application (“Qy”) and the β-lytic protease of Li (“Db”)
PRLB_ACHLY
ID PRLB_ACHLY Reviewed; 374 AA.
AC P27458;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 09-APR-2025, entry version 79.
DE RecName: Full=Beta-lytic metalloendopeptidase;
DE EC=3.4.24.32;
DE AltName: Full=Beta-lytic protease;
DE Flags: Precursor;
OS Achromobacter lyticus.
OC Bacteria; Pseudomonadati; Pseudomonadota; Betaproteobacteria;
OC Burkholderiales; Alcaligenaceae; Achromobacter.
OX NCBI_TaxID=224;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 196-220.
RC STRAIN=M497-1;
RX PubMed=2228973; DOI=10.1128/jb.172.11.6506-6511.1990;
RA Li S.L., Norioka S., Sakiyama F.;
RT "Molecular cloning and nucleotide sequence of the beta-lytic protease gene
RT from Achromobacter lyticus.";
RL J. Bacteriol. 172:6506-6511(1990).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of N-acetylmuramoyl-|-Ala, and of the insulin B chain
CC at 23-Gly-|-Phe-24 > 18-Val-|-Cys(SO3H).; EC=3.4.24.32;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Note=Binds 1 zinc ion per subunit.;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- SIMILARITY: Belongs to the peptidase M23A family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M60896; AAA21906.1; -; Genomic_DNA.
DR PIR; A37151; LYYXLY.
DR AlphaFoldDB; P27458; -.
DR SMR; P27458; -.
DR MEROPS; M23.001; -.
DR KEGG; ag:AAA21906; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd12797; M23_peptidase; 1.
DR Gene3D; 2.70.70.10; Glucose Permease (Domain IIA); 1.
DR InterPro; IPR011055; Dup_hybrid_motif.
DR InterPro; IPR000841; Pept_M23A_Blytic.
DR PRINTS; PR00933; BLYTICPTASE.
DR SUPFAM; SSF51261; Duplicated hybrid motif; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..24
FT PROPEP 25..195
FT /evidence="ECO:0000269|PubMed:2228973"
FT /id="PRO_0000026810"
FT CHAIN 196..374
FT /note="Beta-lytic metalloendopeptidase"
FT /id="PRO_0000026811"
FT REGION 128..187
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 148..164
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 316
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255"
FT BINDING 318
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255"
FT DISULFID 261..307
FT /evidence="ECO:0000250"
FT DISULFID 351..364
FT /evidence="ECO:0000250"
SQ SEQUENCE 374 AA; 40085 MW; 431E51B84575DE14 CRC64;
Query Match 100.0%; Score 1008; Length 374;
Best Local Similarity 100.0%;
Matches 179; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SPNGLLQFPFPRGASWHVGGAHTNTGSGNYPMSSLDMSRGGGWGSNQNGNWVSASAAGSF 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 196 SPNGLLQFPFPRGASWHVGGAHTNTGSGNYPMSSLDMSRGGGWGSNQNGNWVSASAAGSF 255
Qy 61 KRHSSCFAEIVHTGGWSTTYYHLMNIQYNTGANVSMNTAIA NPANTQAQALCNGGQSTGP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 256 KRHSSCFAEIVHTGGWSTTYYHLMNIQYNTGANVSMNTAIA NPANTQAQALCNGGQSTGP 315
Qy 121 HEHWSLKQNGSFYHLNGTYLSGYRITATGSSYDTNCSRFYLTKNGQNYCYGYYVNPGPN 179
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 316 HEHWSLKQNGSFYHLNGTYLSGYRITATGSSYDTNCSRFYLTKNGQNYCYGYYVNPGPN 374
Sequence alignment between the polypeptide of SEQ ID NO:2 of the instant application (“Qy”) and the polypeptide of A0A2U9TAQ8_9GAMM (“Db”)
A0A2U9TAQ8_9GAMM
ID A0A2U9TAQ8_9GAMM Unreviewed; 385 AA.
AC A0A2U9TAQ8;
DT 12-SEP-2018, integrated into UniProtKB/TrEMBL.
DT 12-SEP-2018, sequence version 1.
DT 02-APR-2025, entry version 19.
DE RecName: Full=Beta-lytic metalloendopeptidase {ECO:0008006|Google:ProtNLM};
GN ORFNames=C9I47_2774 {ECO:0000313|EMBL:AWV08445.1};
OS Marilutibacter maris.
OC Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria;
OC Lysobacterales; Lysobacteraceae; Marilutibacter.
OX NCBI_TaxID=1605891 {ECO:0000313|EMBL:AWV08445.1, ECO:0000313|Proteomes:UP000249447};
RN [1] {ECO:0000313|EMBL:AWV08445.1, ECO:0000313|Proteomes:UP000249447}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=HZ9B {ECO:0000313|EMBL:AWV08445.1,
RC ECO:0000313|Proteomes:UP000249447};
RA Zhang X.-Q.;
RT "The complete genome of Lysobacter maris HZ9B, a marine bacterium
RT antagonistic against terrestrial plant pathogens.";
RL Submitted (MAY-2018) to the EMBL/GenBank/DDBJ databases.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000256|PIRSR:PIRSR600841-2};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000256|PIRSR:PIRSR600841-2};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CP029843; AWV08445.1; -; Genomic_DNA.
DR RefSeq; WP_111267476.1; NZ_CP029843.1.
DR AlphaFoldDB; A0A2U9TAQ8; -.
DR KEGG; lmb:C9I47_2774; -.
DR OrthoDB; 6188067at2; -.
DR Proteomes; UP000249447; Chromosome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR CDD; cd12797; M23_peptidase; 1.
DR Gene3D; 2.70.70.10; Glucose Permease (Domain IIA); 1.
DR InterPro; IPR011055; Dup_hybrid_motif.
DR InterPro; IPR000841; Pept_M23A_Blytic.
DR PRINTS; PR00933; BLYTICPTASE.
DR SUPFAM; SSF51261; Duplicated hybrid motif; 1.
PE 4: Predicted;
KW Disulfide bond {ECO:0000256|PIRSR:PIRSR600841-3};
KW Metal-binding {ECO:0000256|PIRSR:PIRSR600841-2};
KW Reference proteome {ECO:0000313|Proteomes:UP000249447};
KW Signal {ECO:0000256|SAM:SignalP}; Zinc {ECO:0000256|PIRSR:PIRSR600841-2}.
FT SIGNAL 1..26
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 27..385
FT /note="Beta-lytic metalloendopeptidase"
FT /evidence="ECO:0000256|SAM:SignalP"
FT /id="PRO_5015913637"
FT ACT_SITE 290
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000256|PIRSR:PIRSR600841-1"
FT ACT_SITE 329
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000256|PIRSR:PIRSR600841-1"
FT BINDING 230
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000256|PIRSR:PIRSR600841-2"
FT BINDING 244
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000256|PIRSR:PIRSR600841-2"
FT BINDING 331
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000256|PIRSR:PIRSR600841-2"
FT DISULFID 274..320
FT /evidence="ECO:0000256|PIRSR:PIRSR600841-3"
FT DISULFID 365..378
FT /evidence="ECO:0000256|PIRSR:PIRSR600841-3"
SQ SEQUENCE 385 AA; 41098 MW; B352D6743773E197 CRC64;
Query Match 77.6%; Score 782.5; Length 385;
Best Local Similarity 78.9%;
Matches 138; Conservative 13; Mismatches 23; Indels 1; Gaps 1;
Qy 3 NGLLQFPFPRGASWHVGGAHTNTGSGNYPMSSLDMSRGGGWGSNQNGNWVSASAAGSFKR 62
|| |||||||| |:|||||| ||||:|||||||| :|||||| | |||||| |||||
Db 211 NGFLQFPFPRGQQWYVGGAHTTTGSGSYPMSSLDMHQGGGWGSYQGDKWVSASAGGSFKR 270
Qy 63 HSSCFAEIVHTGGWSTTYYHLMNIQYNTGANVSMNTAIA NPANTQAQALCNGGQSTGPHE 122
|||||||:|| |||||:|||||||:| |||:|| ||||||||||||||||||| |||||:
Db 271 HSSCFAEVVHGGGWSTSYYHLMNIRYGTGASVSANTAIA NPANTQAQALCNGGHSTGPHQ 330
Qy 123 HWSLKQNGSFYHLNGTYLSGYRITA-TGSSYDTNCSRFYLTKNGQNYCYGYYVNP 176
||||| ||| ||||| ||||::||| : |||||||||||:||| || ||: ||
Db 331 HWSLKYNGSHYHLNGVYLSGFQITAISNQSYDTNCSRFYLSKNGYRYCAGYFYNP 385
Sequence alignment between the polypeptide of SEQ ID NO:2 of the instant application (“Qy”) and the polypeptide of Hioki (“Db”)
BGP56827
ID BGP56827 standard; protein; 178 AA.
XX
AC BGP56827;
XX
DT 19-SEP-2019 (first entry)
XX
DE Lysobacter gummosus LgBLP mature protein, SEQ ID 10.
XX
KW BLP protein; beta-lytic metallopeptidase; degradation; enzyme production;
KW fermentation.
XX
OS Lysobacter gummosus.
XX
FH Key Location/Qualifiers
FT Protein 1..178
FT /label= BLP_mature_protein
XX
CC PN WO2019142773-A1.
XX
CC PD 25-JUL-2019.
XX
CC PF 15-JAN-2019; 2019WO-JP000894.
XX
PR 16-JAN-2018; 2018JP-00005193.
PR 16-JAN-2018; 2018JP-00005194.
PR 22-NOV-2018; 2018JP-00219142.
XX
CC PA (KAOS ) KAO CORP.
XX
CC PI Hioki T, Yamashita D, Tohata M;
XX
DR WPI; 2019-646855/61.
DR N-PSDB; BGP56828, BGP56829.
XX
CC PT Producing M23A family protease involves culturing Bacillus introduced
CC PT with polynucleotide encoding pro-protein of M23A family protease, and
CC PT producing mature M23A family protease outside Bacillus.
XX
CC PS Claim 2; SEQ ID NO 10; 58pp; Japanese.
XX
CC The present invention relates to a method for producing protease of the
CC M23A family. The method involves: (1) culturing a Bacillus bacterium into
CC which a polynucleotide encoding a proprotein of M23A family protease is
CC introduced; and (2) producing a mature M23A family protease outside of
CC the Bacillus bacterium. The M23 family proteases have the activity of
CC degrading elastin and bacterial cell wall proteoglycans and are also
CC known as lytic enzymes. M23 family proteases are classified into two
CC subfamilies: the M23A subfamily and the M23B subfamily.
XX
SQ Sequence 178 AA;
Query Match 88.7%; Score 894; Length 178;
Best Local Similarity 89.3%;
Matches 158; Conservative 6; Mismatches 13; Indels 0; Gaps 0;
Qy 1 SPNGLLQFPFPRGASWHVGGAHTNTGSGNYPMSSLDMSRGGGWGSNQNGNWVSASAAGSF 60
|||||||||||||| ||||||||||||||||||||||| ||||||||: |||||| |||
Db 1 SPNGLLQFPFPRGARWHVGGAHTNTGSGNYPMSSLDMSLGGGWGSNQSNTWVSASANGSF 60
Qy 61 KRHSSCFAEIVHTGGWSTTYYHLMNIQYNTGANVSMNTAIA NPANTQAQALCNGGQSTGP 120
||||||||||||:|||||||||||||:||||||| ||||||||||:|||||||| ||||
Db 61 KRHSSCFAEIVHSGGWSTTYYHLMNIRYNTGANVGSNTAIA NPANTRAQALCNGGSSTGP 120
Qy 121 HEHWSLKQNGSFYHLNGTYLSGYRITATGSSYDTNCSRFYLTKNGQNYCYGYYVNPG 177
||||||| ||||||||| ||||||||||||||||||||||| ||||||| |:: |||
Db 121 HEHWSLKLNGSFYHLNGAYLSGYRITATGSSYDTNCSRFYLAKNGQNYCSGWFTNPG 177