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/EP2019/086425.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on June 12, 2026 has been entered.
Election/Restrictions
Applicant elected without traverse of Group I with a species election of A2C8 mutant trypsin (SEQ ID NO:1 as the parent polypeptide and Y39H, Y59H, K60E, D189K, H40F, R96E, K97D, L99F, N143E, E151Y, S190V, Q192A, S214G, G219Q, and A221T amino acid substitutions made in the parent) in the reply filed on October 6, 2023.
The elected species, A2C8 mutant trypsin (mutant of SEQ ID NO:1, wherein the mutant consists of Y39H, Y59H, K60E, D189K, H40F, R96E, K97D, L99F, N143E, E151Y, S190V, Q192A, S214G, G219Q, and A221T amino acid substitutions (correlating to chymotrypsin nomenclature), is free of the prior art. Therefore, examination has been extended to subsequent species, a mutant trypsin of SEQ ID NO:1, wherein said mutant comprises K60E + D189K +N143H + E151H or K60E + D189K +Y39H + Y59H (correlating to chymotrypsin nomenclature), which are disclosed in the prior art. See the rejections under 102 in the Office Action mailed on July 19, 2024. The amendment filed on December 19, 2024 amended the claims to require at least 6 amino acid substitutions recited in claim 1. Thus, examination has been extended to a subsequent species comprising a combination of at least six amino acid substitutions recited in claim 1.
Claims 2 and 27-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on October 6, 2023.
Status of Claims
Claims 1-2, 15-25, and 27-28 are pending.
Claims 2 and 27-28 are withdrawn.
Claims 1 and 15-25 are under examination.
Response to Amendments/Arguments
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.
Claim 1 and claims 15-25 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 1 recites the phrase “mutated trypsin comprising SEQ ID NO:1 with at least six (6) amino acid substitutions..”. The metes and bounds of the phrase in the context of the claims are not clear. It is unclear how a polypeptide can comprise the amino acid sequence of SEQ ID NO:1 and also have amino acid substitutions. A polypeptide either has the amino acid sequence of a given sequence identifier or it does not. Appropriate correction is required.
For examination purposes, the phrase has been interpreted as “A trypsin mutant of SEQ ID NO:1, wherein the trypsin mutant comprises at least six (6) amino acid substitutions…”.
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 1 and 15-25 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 trypsin mutant of SEQ ID NO:1, wherein the trypsin mutant comprises a combination of at least six amino acid substitutions recited in claim 1, optionally the amino acid substitutions recited in claims 15-25, and any other amino acid modifications, wherein the trypsin mutant has increased affinity for any nucleophilic substrates and/or reduced hydrolysis activity compared to the trypsin of SEQ ID NO:1. Therefore, the claims are directed to a genus of trypsin mutants having unknown structure but having the function of having increased affinity for any nucleophilic substrates and/or reduced hydrolysis activity compared to the trypsin of SEQ ID NO:1.
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 “increased affinity for the nucleophilic substrate” and “reduced hydrolysis activity” fails to provide a sufficient description of the genus of the trypsin mutant 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.
Rat anionic trypsin II having 100% sequence identity to the Rat anionic trypsin II of SEQ ID NO:1 of the instant application was known in the art, see TRY2_RAT (UnitProtKB/Swiss-Prot. October 25, 2017 – cited previously on form PTO-892 and the sequence alignment below). However, trypsin mutants having unknown structure but having increased affinity for any nucleophilic substrates and/or reduced hydrolysis activity were not known in the art.
Fransceus (J Ind Microbiol Biotechnol. 2017 May;44(4-5):687-695. – cited previously on 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. – cited previously on 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 a trypsin mutant of SEQ ID NO:1, wherein the trypsin mutant consists of H23F/Y, A38A/V/S/T, R78E/P, K79H/D/F, L81F/Y/W/M, N123V/D/E/T, E131D/A/T/Y, S172A/V, Q174A/V/F/W, S192G/A, G196Q/P, and A198Q/T which correlate to chymosin nomenclature of H40, A55, R96, K97, L99, N143, E151, S190, Q192, S214, G219, and A221 (see Table 4 at pages 23-24 of the specification and Table 5 at pages) and wherein the trypsin mutant has increased affinity for a nucleophilic substrates and reduced hydrolysis activity compared to the trypsin of SEQ ID NO:1. 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 trypsin mutant of SEQ ID NO:1 described 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.
Further, with the aid of a computer, one of skill in the art could identify mutants of SEQ ID NO:1. However, there is no teaching regarding which amino acids of the trypsin of SEQ ID NO:1, other than H23F/Y, A38A/V/S/T, R78E/P, K79H/D/F, L81F/Y/W/M, N123V/D/E/T, E131D/A/T/Y, S172A/V, Q174A/V/F/W, S192G/A, G196Q/P, and A198Q/T, that can be modified and result in polypeptide having increased affinity for a nucleophilic substrates and reduced hydrolysis activity compared to the unmodified trypsin.
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 claims 1 and 15-25.
Applicant's arguments filed June 12, 2026 have been fully considered but they are not persuasive.
Applicant argues the amendment of claim 1 meets the written description requirement because amended claim 1 clarifies that the claimed mutated trypsin comprises SEQ ID NO:1 with at least six (6) amino acid substitutions.
This is not found persuasive. The claims are not limited to a trypsin mutant of SEQ ID NO:1, wherein the trypsin mutant consists of the amino acid substitutions recited in claim 1. Instead, the claims are directed to any trypsin mutants of SEQ ID NO:1, wherein the trypsin mutants comprise 6 or more amino acid substitutions, optionally the amino acid substitutions recited in claims 15-25, and any other amino acid modifications, wherein the trypsin mutants have increased affinity for any nucleophilic substrates and/or reduced hydrolysis activity compared to the trypsin of SEQ ID NO:1.
One of skill in the art could identify mutants of SEQ ID NO:1. However, there is no teaching regarding which amino acids of the trypsin of SEQ ID NO:1, other than H23F/Y, A38A/V/S/T, R78E/P, K79H/D/F, L81F/Y/W/M, N123V/D/E/T, E131D/A/T/Y, S172A/V, Q174A/V/F/W, S192G/A, G196Q/P, and A198Q/T, that can be modified and result in polypeptide having increased affinity for a nucleophilic substrates and reduced hydrolysis activity compared to the unmodified trypsin.
Fransceus (J Ind Microbiol Biotechnol. 2017 May;44(4-5):687-695. – cited previously on 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. – cited previously on 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 a trypsin mutant of SEQ ID NO:1, wherein the mutant trypsin consists of H23F/Y, A38A/V/S/T, R78E/P, K79H/D/F, L81F/Y/W/M, N123V/D/E/T, E131D/A/T/Y, S172A/V, Q174A/V/F/W, S192G/A, G196Q/P, and A198Q/T which correlate to chymosin nomenclature of H40, A55, R96, K97, L99, N143, E151, S190, Q192, S214, G219, and A221 (see Table 4 at pages 23-24 of the specification and Table 5 at pages) and wherein the trypsin mutant has increased affinity for a nucleophilic substrates and reduced hydrolysis activity compared to the trypsin of SEQ ID NO:1. Therefore, the specification fails to describe a representative species of the claimed genus.
Hence the rejection is maintained.
Conclusion
Claims 1-2, 15-25, and 27-28 are pending.
Claims 2 and 27-28 are withdrawn.
Claims 1 and 15-25 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 of SEQ ID NO:1 of the instant application (“Qy”) and the trypsin of TRY2_RAT (“Db”)
TRY2_RAT
ID TRY2_RAT Reviewed; 246 AA.
AC P00763;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 13-SEP-2023, entry version 206.
DE RecName: Full=Anionic trypsin-2;
DE EC=3.4.21.4;
DE AltName: Full=Anionic trypsin II;
DE AltName: Full=Pretrypsinogen II;
DE AltName: Full=Serine protease 2;
DE Flags: Precursor;
GN Name=Prss2; Synonyms=Try2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6094547; DOI=10.1016/s0021-9258(18)89886-6;
RA Craik C.S., Choo Q.L., Swift G.H., Quinto C., MacDonald R.J., Rutter W.J.;
RT "Structure of two related rat pancreatic trypsin genes.";
RL J. Biol. Chem. 259:14255-14264(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 9-246.
RC STRAIN=Sprague-Dawley; TISSUE=Pancreas;
RX PubMed=6896710; DOI=10.1016/s0021-9258(18)34133-4;
RA MacDonald R.J., Stary S.J., Swift G.H.;
RT "Two similar but nonallelic rat pancreatic trypsinogens. Nucleotide
RT sequences of the cloned cDNAs.";
RL J. Biol. Chem. 257:9724-9732(1982).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=3112942; DOI=10.1126/science.3112942;
RA Sprang S., Standing T., Fletterick R.J., Stroud R.M., Finer-Moore J.,
RA Xuong N.-H., Hamlin R., Rutter W.J., Craik C.S.;
RT "The three-dimensional structure of Asn102 mutant of trypsin: role of
RT Asp102 in serine protease catalysis.";
RL Science 237:905-909(1987).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.59 ANGSTROMS).
RX PubMed=1881877; DOI=10.1002/prot.340100303;
RA Earnest T., Fauman E., Craik C.S., Stroud R.;
RT "1.59-A structure of trypsin at 120 K: comparison of low temperature and
RT room temperature structures.";
RL Proteins 10:171-187(1991).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
RX PubMed=8634241; DOI=10.1021/bi9530200;
RA Brinen L.S., Willett W.S., Craik C.S., Fletterick R.J.;
RT "X-ray structures of a designed binding site in trypsin show metal-
RT dependent geometry.";
RL Biochemistry 35:5999-6009(1996).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.; EC=3.4.21.4;
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Note=Binds 1 Ca(2+) ion per subunit.;
CC -!- INTERACTION:
CC P00763; P23827: eco; Xeno; NbExp=2; IntAct=EBI-1029166, EBI-1029159;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; V01274; CAA24581.1; -; mRNA.
DR EMBL; L00131; AAA98517.1; -; mRNA.
DR EMBL; L00130; AAA98517.1; JOINED; Genomic_DNA.
DR PIR; A22657; TRRT2.
DR RefSeq; NP_036861.1; NM_012729.2.
DR PDB; 1AMH; X-ray; 2.50 A; A/B=24-246.
DR PDB; 1ANB; X-ray; 2.80 A; A=24-246.
DR PDB; 1ANC; X-ray; 2.20 A; A=24-246.
DR PDB; 1AND; X-ray; 2.30 A; A=24-246.
DR PDB; 1ANE; X-ray; 2.20 A; A=24-246.
DR PDB; 1BRA; X-ray; 2.20 A; A=24-246.
DR PDB; 1BRB; X-ray; 2.10 A; E=24-246.
DR PDB; 1BRC; X-ray; 2.50 A; E=24-246.
DR PDB; 1CO7; X-ray; 1.90 A; E=2-246.
DR PDB; 1DPO; X-ray; 1.59 A; A=24-246.
DR PDB; 1EZS; X-ray; 2.30 A; C/D=24-246.
DR PDB; 1EZU; X-ray; 2.40 A; C/D=24-246.
DR PDB; 1F5R; X-ray; 1.65 A; A=15-246.
DR PDB; 1F7Z; X-ray; 1.55 A; A=15-246.
DR PDB; 1FY8; X-ray; 1.70 A; E=15-246.
DR PDB; 1J14; X-ray; 2.40 A; A=24-246.
DR PDB; 1J15; X-ray; 2.00 A; A=24-246.
DR PDB; 1J16; X-ray; 1.60 A; A=24-246.
DR PDB; 1J17; X-ray; 2.00 A; T=24-246.
DR PDB; 1K9O; X-ray; 2.30 A; E=24-246.
DR PDB; 1QL9; X-ray; 2.30 A; A=24-246.
DR PDB; 1SLU; X-ray; 1.80 A; B=24-246.
DR PDB; 1SLV; X-ray; 2.30 A; B=24-246.
DR PDB; 1SLW; X-ray; 2.00 A; B=24-246.
DR PDB; 1SLX; X-ray; 2.20 A; B=24-246.
DR PDB; 1TRM; X-ray; 2.30 A; A/B=24-246.
DR PDB; 1YKT; X-ray; 1.70 A; A=24-246.
DR PDB; 1YLC; X-ray; 1.70 A; A=24-246.
DR PDB; 1YLD; X-ray; 1.70 A; A=24-246.
DR PDB; 2TRM; X-ray; 2.80 A; A=24-246.
DR PDB; 3FP6; X-ray; 1.49 A; E=24-246.
DR PDB; 3FP7; X-ray; 1.46 A; E=24-246.
DR PDB; 3FP8; X-ray; 1.46 A; E=24-246.
DR PDB; 3TGI; X-ray; 1.80 A; E=24-246.
DR PDB; 3TGJ; X-ray; 2.20 A; E=15-246.
DR PDB; 3TGK; X-ray; 1.70 A; E=15-246.
DR PDBsum; 1AMH; -.
DR PDBsum; 1ANB; -.
DR PDBsum; 1ANC; -.
DR PDBsum; 1AND; -.
DR PDBsum; 1ANE; -.
DR PDBsum; 1BRA; -.
DR PDBsum; 1BRB; -.
DR PDBsum; 1BRC; -.
DR PDBsum; 1CO7; -.
DR PDBsum; 1DPO; -.
DR PDBsum; 1EZS; -.
DR PDBsum; 1EZU; -.
DR PDBsum; 1F5R; -.
DR PDBsum; 1F7Z; -.
DR PDBsum; 1FY8; -.
DR PDBsum; 1J14; -.
DR PDBsum; 1J15; -.
DR PDBsum; 1J16; -.
DR PDBsum; 1J17; -.
DR PDBsum; 1K9O; -.
DR PDBsum; 1QL9; -.
DR PDBsum; 1SLU; -.
DR PDBsum; 1SLV; -.
DR PDBsum; 1SLW; -.
DR PDBsum; 1SLX; -.
DR PDBsum; 1TRM; -.
DR PDBsum; 1YKT; -.
DR PDBsum; 1YLC; -.
DR PDBsum; 1YLD; -.
DR PDBsum; 2TRM; -.
DR PDBsum; 3FP6; -.
DR PDBsum; 3FP7; -.
DR PDBsum; 3FP8; -.
DR PDBsum; 3TGI; -.
DR PDBsum; 3TGJ; -.
DR PDBsum; 3TGK; -.
DR AlphaFoldDB; P00763; -.
DR SMR; P00763; -.
DR BioGRID; 247129; 1.
DR DIP; DIP-6112N; -.
DR IntAct; P00763; 2.
DR MINT; P00763; -.
DR STRING; 10116.ENSRNOP00000018853; -.
DR BindingDB; P00763; -.
DR ChEMBL; CHEMBL4290; -.
DR MEROPS; S01.119; -.
DR iPTMnet; P00763; -.
DR PhosphoSitePlus; P00763; -.
DR PaxDb; P00763; -.
DR Ensembl; ENSRNOT00000095908; ENSRNOP00000082459; ENSRNOG00000064731.
DR GeneID; 25052; -.
DR KEGG; rno:25052; -.
DR UCSC; RGD:3418; rat.
DR AGR; RGD:3418; -.
DR CTD; 5645; -.
DR RGD; 3418; Prss2.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT01050000244883; -.
DR HOGENOM; CLU_006842_7_0_1; -.
DR InParanoid; P00763; -.
DR OMA; HPRYSSW; -.
DR OrthoDB; 4629979at2759; -.
DR PhylomeDB; P00763; -.
DR Reactome; R-RNO-1442490; Collagen degradation.
DR Reactome; R-RNO-1462054; Alpha-defensins.
DR Reactome; R-RNO-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-6803157; Antimicrobial peptides.
DR SABIO-RK; P00763; -.
DR EvolutionaryTrace; P00763; -.
DR PRO; PR:P00763; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000032916; Expressed in pancreas and 10 other tissues.
DR Genevisible; P00763; RN.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0030574; P:collagen catabolic process; ISS:UniProtKB.
DR GO; GO:0007586; P:digestion; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR PANTHER; PTHR24264:SF10; PROTEASE, SERINE 1 (TRYPSIN 1)-RELATED; 1.
DR PANTHER; PTHR24264; TRYPSIN-RELATED; 1.
Query Match 100.0%; Score 1212; Length 246;
Best Local Similarity 100.0%;
Matches 223; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 IVGGYTCQENSVPYQVSLNSGYHFCGGSLINDQWVVSAAHCYKSRIQVRLGEHNINVLEG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 24 IVGGYTCQENSVPYQVSLNSGYHFCGGSLINDQWVVSAAHCYKSRIQVRLGEHNINVLEG 83
Qy 61 NEQFVNAAKIIKHPNFDRKTLNNDIMLIKLSSPVKLNARVATVALPSSCAPAGTQCLISG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 84 NEQFVNAAKIIKHPNFDRKTLNNDIMLIKLSSPVKLNARVATVALPSSCAPAGTQCLISG 143
Qy 121 WGNTLSSGVNEPDLLQCLDAPLLPQADCEASYPGKITDNMVCVGFLEGGKDSCQGDSGGP 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 144 WGNTLSSGVNEPDLLQCLDAPLLPQADCEASYPGKITDNMVCVGFLEGGKDSCQGDSGGP 203
Qy 181 VVCNGELQGIVSWGYGCALPDNPGVYTKVCNYVDWIQDTIAAN 223
|||||||||||||||||||||||||||||||||||||||||||
Db 204 VVCNGELQGIVSWGYGCALPDNPGVYTKVCNYVDWIQDTIAAN 246
a
Prosecution Insights