DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/17/2025 has been entered.
Claims 1, 7-9, 12-27, 29, 32-33, 35-43 and 47-50 are pending in this application.
Applicant’s amendment to the claims filed 12/17/2025 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s remarks filed on 12/17/2025 in response to the final rejection mailed on 09/15/2025 are acknowledged and have been fully considered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election
The elected subject matter is:
Species (A1), the exopeptidase comprises a sequence having at least 70%, 80%, 85%, 90%, 95% or 99% sequence identity, or a sequence according to MalProII (SEQ ID NO: 1), or an active fragment thereof,
Species (B1), the aminopeptidase comprises a sequence having at least 70%, 80%, 85%, 90%, 95% or 99% sequence identity, or a sequence according to SEQ ID NO: 10, or an aminopeptidase active fragment thereof, and
Species (C1), the endopeptidase comprises a sequence having at least 70%, 80%, 85%, 90%, 95% or 99% sequence identity, or a sequence according to SEQ ID NO: 18, or an endopeptidase active fragment thereof
elected in the reply filed 04/22/2024.
Claims 1, 7-9, 12-27, 29, 32-33, 35-43 and 47-50 are being examined on the merits only to the extent they read on the elected subject matter.
In view of the elected species of an exopeptidase comprising a sequence having at least 70%, 80%, 85%, 90%, 95% or 99% sequence identity, or a sequence according to MalProII (SEQ ID NO: 1), or an active fragment thereof being free of the prior art of record, the search and examination has been extended in accordance with MPEP 803.02.III.A to the species of an exopeptidase comprising a sequence having at least 70%, 80%, 85%, 90%, 95% or 99% sequence identity, or a sequence according to SEQ ID NO: 3, or an active fragment thereof.
Claim Objections
Claim 1 is objected to for the phrase “A method for preparing a protein hydrolysate from a proteinaceous material wherein the proteinaceous material comprises a vegetable derived protein, an animal derived protein, a fish derived protein, an insect derived protein or a microbial derived protein, comprising contacting the proteinaceous material…”. In the interest of improving claim form, Applicant should consider an amendment to recite “A method for preparing a protein hydrolysate from a proteinaceous material, wherein the proteinaceous material comprises a vegetable derived protein, an animal derived protein, a fish derived protein, an insect derived protein or a microbial derived protein, wherein the method comprises contacting the proteinaceous material”.
Claim 1 recites multiple limitations which include a plurality of steps, such as “contacting the proteinaceous material under aqueous conditions…” in line 4 and “wherein the method further comprises” in line 14. As set forth in 37 CFR 1.75(i), where a claim sets forth a plurality of steps, each step of the claim should be separated by a line indentation (see MPEP 608.01(i)).
Claim 49 is objected to for the phrase “peptides bearing an N-terminal XPQQP motif”, wherein XPQQP is identified as SEQ ID NO: 30. 37 CFR 1.831(c) requires that each amino acid sequence set forth in a "Sequence Listing XML" in accordance with 37 CFR § 1.831(a) must be referenced by a sequence identifier as defined in 37 CFR 1.832(a) (see MPEP § 2412.05(a)), preceded by the notation "SEQ ID NO:" or the like, when the sequence appears in the description or claims.
Claim Rejections - 35 USC § 112(b)
Claims 47-50 are newly rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
The instant rejection is newly stated and necessitated by claim amendment.
Claim 47 recites the phrase “the exopeptidase cleaves the pentapeptide Gln-Pro-Gln-Gln-Pro (SEQ ID NO: 9)” as determined by a primary-amine detection assay. It is unclear whether the wherein clause recited in claim 47 is intended to require performing the method set forth in claim 1 within the metes and bounds of claim 1, whether it is intended to further limit the method of claim 1 to include the performing of the analysis to determine the cleavage of the pentapeptide of SEQ ID NO: 9, whether it is intended to further limit the properties of the produced hydrolysate, or whether it is intended to further limit the properties of the recited exopeptidase. As set forth in MPEP 2111.04.I, “wherein” clauses raise the question as to the limiting effect of the language in a claim, and as such the metes and bounds of the instant claim are unclear.
Additionally, as claim 1 recites two exopeptidases, it is unclear which of the two previously recited exopeptidases is being referred to from the recitation of “the exopeptidase” in claim 47.
Claim 48 recites the phrases “the amino acid peak” in line 4, “the DP2-DP5 peak” in line 4, and “said control” in line 5. There is insufficient antecedent basis for these limitations in the claim.
Claim 48 is rejected for the phrase “wherein the protein hydrolysate exhibits at least a 20% to 70% increase in free glutamic acid concentration relative to an otherwise identical process lacking the exopeptidase, and a size-exclusion chromatograph with charged-aerosol detection (SEC/CAD) in which the amino acid peak area is greater than or equal to 1.3X and the DP2-DP5 peak area is less than or equal to 0.77X that of said control”. It is unclear whether the wherein clause recited in claim 48 is intended to require performing the method set forth in claim 1 within the metes and bounds of claim 1, whether it is intended to further limit the method of claim 1 to include the performing of the analysis to determine the free glutamic acid content and SEC/CAD peaks, or whether it is intended to further limit the properties of the produced hydrolysate. As set forth in MPEP 2111.04.I, “wherein” clauses raise the question as to the limiting effect of the language in a claim, and as such the metes and bounds of the instant claim are unclear.
Additionally, as claim 1 recites two exopeptidases, it is unclear from the recitation of “lacking the exopeptidase” in claim 48 which of the two previously recited exopeptidases is required as lacking.
Claim 49 is rejected for the phrase “wherein the abundance of peptides bearing an N-terminal motif XPQQP is reduced by at least 50% relative to an otherwise identical process lacking the exopeptidase, as determined by peptide sequencing or mass-spectrometric peptide analysis”. It is unclear whether the wherein clause recited in claim 49 is intended to require performing the method set forth in claim 1 within the metes and bounds of claim 1, whether it is intended to further limit the method of claim 1 to include performing of the analysis to determine the reduction of peptides bearing an N-terminal motif XPQQP, or whether it is intended to further limit the properties of the produced hydrolysate. As set forth in MPEP 2111.04.I, “wherein” clauses raise the question as to the limiting effect of the language in a claim, and as such the metes and bounds of the instant claim are unclear.
Additionally, as claim 1 recites two exopeptidases, it is unclear from the recitation of “lacking the exopeptidase” in claim 49 which of the two previously recited exopeptidases is required as lacking.
Claim 50 recites the phrase “[t]he method of claim 1, wherein said contacting comprises simultaneous contacting with an endopeptidase, said exopeptidase, and said aminopeptidase”. As set forth in MPEP 2111.04.I, “wherein” clauses raise the question as to the limiting effect of the language in a claim. It is unclear whether the “wherein” clause recited in claim 50 is intended to require performing the method set forth in claim 1 within the metes and bounds of claim 1, or whether the “wherein” clause is merely intended to further limit the method of claim 1 to comprise an endopeptidase. As claim 1 does not recite an endopeptidase, the metes and bounds of the instant claim are unclear and it is suggested that applicant clarify the meaning of claim 50.
Claim Rejections - 35 USC § 101
The rejection of claims 1 and 7-9 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 is withdrawn in view of the amendment to claim 1 to recite a step of inactivating enzymatic activity and recovering the protein hydrolysate by solid-liquid separation and membrane filtration, as the amendment to claim 1 to include this step establishes the claimed method as markedly different from its naturally occurring counterpart.
Claim Rejections - 35 USC § 103
The rejection of claims 1 and 7-9 under 35 U.S.C. 103 as being unpatentable over Kikkoman et al. (JP 2003/219888A; reference is made to the machine translation cited on the IDS submitted 02/06/2023; herein referred to as Kikkoman) in view of NCBI Accession No. XP_024745139.1 (2 pages, 04/27/2018; cited on the Form PTO-892 mailed 01/27/2025; herein referred to as NCBI4),
the rejection of claims 12-19 under 35 U.S.C. 103 as being unpatentable over Kikkoman in view of NCBI4 as applied to claims 1 and 7-9 above, and further in view of NCBI Accession No. EAW12353.1 (2 pages, 7/14/2016; cited on the Form PTO-892 mailed 06/28/2024; herein referred to as NCBI2),
the rejection of claim 20 under 35 U.S.C. 103 as being unpatentable over Kikkoman in view of NCBI4 and NCBI2 as applied to claims 1, 7-9 and 12-19 above, and further in view of Merz et al. (J Mol Cat B Enzymatic, 2016, 127:1; cited on the Form PTO-892 mailed 01/27/2025; herein referred to as Merz),
the rejection of claims 21-27, 29, 32-33, 35 and 43 under 35 U.S.C. 103 as being unpatentable over Kikkoman in view of NCBI4, NCBI2, and Merz as applied to claims 1, 7-9 and 12-20 above, and further in view NCBI Accession No. AFT92040.1 (2 pages, 05/28/2013; cited on the Form PTO-892 mailed 06/28/2024; herein referred to as NCBI3), and
the rejection of claims 36-42 under 35 U.S.C. 103 as being unpatentable over Kikkoman in view of NCBI4, NCBI2, Merz and NCBI3 as applied to claims 1, 7-9 and 12-27, 29, 32-33, 35, and 43 above, and further in view UniProt Accession No. A0A1Y0XA48_BACAM (1 page, 10/25/2017; cited on the Form PTO-892 mailed 06/28/2024; herein referred to as UNI1)
are withdrawn in view of the amendment to claim 1 to recite “after said contacting, inactivating enzymatic activity and recovering the protein hydrolysate by solid-liquid separation and membrane filtration”
Claims 1, 7-9, and 47-50 are newly rejected under 35 U.S.C. 103 as being unpatentable over Kikkoman in view of NCBI4 and Vioque et al. (JAOCS, 1999, 76:819; cited on the attached Form PTO-892; herein referred to as Vioque).
The instant rejection is newly stated and necessitated by claim amendment.
Claim 1 is drawn to a method for preparing a protein hydrolysate from a proteinaceous material,
wherein the proteinaceous material comprises a vegetable derived protein, an animal derived protein, a fish derived protein, an insect derived protein or a microbial derived protein,
the method comprising contacting the proteinaceous material under aqueous conditions with a proteolytic enzyme combination comprising an exopeptidase specific for peptides having as an N-terminus a five amino acid sequence as set forth in SEQ ID NO: 30, wherein X is the amino terminal amino acid and can be any naturally occurring amino acid,
wherein the exopeptidase comprises a sequence having at least 90% sequence identity to one of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ IDNO: 4 and SEQ ID NO: 5 or an active fragment of a sequence having at least 90% sequence identity to one of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4 and SEQ ID NO:5,
wherein the proteolytic enzyme combination further comprises a second exopeptidase and wherein the second exopeptidase is an aminopeptidase,
wherein at least one enzyme of the proteolytic enzyme combination is provided as an isolated and purified preparation by recombinant expression in Trichoderma or Bacillus,
and the method further comprises, after said contacting, inactivating enzymatic activity and recovering the protein hydrolysate by solid-liquid separation and membrane filtration.
As noted above, the elected species of an exopeptidase comprising a sequence having at least 70%, 80%, 85%, 90%, 95% or 99% sequence identity, or a sequence according to MalProII (SEQ ID NO: 1), or an active fragment thereof is free of the prior art and the search and examination has been extended to the species of an exopeptidase comprising a sequence having at least 70%, 80%, 85%, 90%, 95% or 99% sequence identity, or a sequence according to SEQ ID NO: 3, or an active fragment thereof.
The limitation “wherein at least one enzyme of the proteolytic enzyme combination is provided as an isolated and purified preparation by recombinant expression in Trichoderma or Bacillus” is considered to be a Product-by-Process limitation according to MPEP 2113, wherein the “at least one enzyme of the proteolytic enzyme combination” is only limited by the structure implied by the steps of its production.
Kikkoman describes methods for producing aminopeptidase P [title].
Regarding claims 1 and 7-9, Kikkoman discloses during soy sauce production that raw material is decomposed into a polypeptide by a series of proteases including leucine aminopeptidase to decompose the peptide from the amino terminus, acidic carboxypeptidase to decompose the peptide from the carboxy terminus [para 0005], and wherein another protease involved is aminopeptidase P [EC 3.4.11.9 described in para 0002], which releases the N-terminal amino acid from peptides wherein Pro is the second amino acid from the N-terminus [para 0002]. Therefore Kikkoman describes a method of creating a protein hydrolysate by digesting peptides with three exopeptidases: leucine aminopeptidase, aminopeptidase P, and acidic carboxypeptidase, wherein two of these exopeptidases are aminopeptidases. As such, the method of Kikkoman encompasses the limitations in claim 1 of a method for preparing a protein hydrolysate with an enzyme mixture comprising an exopeptidase and further comprising a second exopeptidase, wherein the second exopeptidase is an aminopeptidase.
Regarding claim 1 and the limitation of the proteinaceous material comprises a vegetable derived protein, an animal derived protein, a fish derived protein, an insect derived protein or a microbial derived protein, Kikkoman discloses during soy sauce production that raw material is decomposed into a polypeptide by a series of proteases [para 0005], wherein the raw material is understood to be proteinaceous material from the soybean vegetable.
Regarding claim 1 and the limitation “wherein at least one enzyme of the proteolytic enzyme combination is provided as an isolated and purified preparation by recombinant expression in Trichoderma or Bacillus”, this limitation is considered to be a Product-by-Process limitation as set forth above, and therefore the aminopeptidase of Kikkoman is considered to satisfy the structural limitations of the “at least one enzyme of the proteolytic enzyme combination” recited in the claim.
Kikkoman does not teach the sequence of an exopeptidase, the associated functional limitations of the claim and the step of inactivating enzymatic activity and recovering the protein hydrolysate by solid-liquid separation and membrane filtration.
NCBI4 discloses an enzyme from Trichoderma citrinoviride annotated as an X-Prolyl Aminopeptidase classified as EC 3.4.11.9 which catalyzes the release of any N-terminal amino acid linked with proline [p 2], wherein the enzyme shares 100% sequence identity with SEQ ID NO: 3 [see Appendix A]. As the sequence is encompassed by the claims, it is therefore presumed to have the recited functional limitations as being specific for peptides containing the N-terminal amino acid sequence XPQQP (see MPEP 2112.01.I), as the recited function of the enzyme is presumed to be inherent to its structure.
Vioque relates to production and characterization of rapeseed protein hydrolysate [title], wherein rapeseed is understood to be a vegetable derived protein, and discusses that protein hydrolysates have improved properties to the proteins they are derived from and make them a good source of protein in human nutrition [p 819, col 1, para 2].
Regarding claim 1 and the limitation of inactivating enzymatic activity and recovering the protein hydrolysate by solid-liquid separation and membrane filtration, Vioque teaches that protein hydrolysates may undergo further modification, such as fractionation to obtain tailor-made protein hydrolysates for the fortification of specific clinical diets [p 819, col 1, para 2], and teaches a method of hydrolyzing a protein isolate with a protease mixture, stopping hydrolysis by lowering pH to 5 corresponding to enzyme inactivation, and the separation of hydrolysate from insoluble fragments corresponding to solid-liquid separation [p 820, col 1, para 4, “Hydrolysis” section]. Vioque teaches that protein hydrolysate can also be fractionated by membrane technology such as ultrafiltration in order to useful for further modification of clinical diets [p 822, col 2, para 4].
In view of NCBI4, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Kikkoman by using enzyme of NCBI4 to arrive at the claimed invention, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the aminopeptidase P of Kikkoman and the enzyme of NCBI4 are both EC 3.4.11.9 enzymes capable of cleaving an N-terminal amino acid connected to proline, and as such both are capable of being incorporated into the method as described by Kikkoman. Thus it would have been obvious to one of ordinary skill in the art to replace the aminopeptidase P of Kikkoman with the enzyme X-prolyl aminopeptidase of NCBI4, as one of ordinary skill in the art would have been able to carry out such a substitution with reasonable expectation of success because both Kikkoman and NCBI4 relate to EC 3.4.11.9 enzymes.
In view of Vioque, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Kikkoman by inactivating the enzymes and separating the hydrolysate as taught by Vioque to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the method of Kikkoman by inactivating the enzymes and separating the hydrolysate because Vioque teaches protein hydrolysates have improved properties to the proteins they are derived from and make them a good source of protein in human nutrition, and can be fractionated to obtain tailor-made protein hydrolysates for the fortification of specific clinical diets. One of ordinary skill in the art would have had a reasonable expectation of success because both Kikkoman and Vioque relate to the production of protein hydrolysates from vegetable sources.
Regarding claim 47, in view of the indefiniteness of the “wherein” clause set forth in the rejection of the instant claim under 35 USC 112(b) above, and for the sake of compact prosecution, the limitations of the instant claim are being interpreted as further limiting the exopeptidase of SEQ ID NO: 3 recited in claim 1. As the aminopeptidase of NCBI4 shares 100% sequence identity with SEQ ID NO: 3 [see Appendix A], and is therefore encompassed by the claims, it is presumed to have the recited functional limitation of cleaving the pentapeptide of SEQ ID NO: 19 as determined by primary-amine detection assay (see MPEP 2112.01.I), as the recited function of the enzyme is presumed to be inherent to its structure. Regarding claim 48, in view of the indefiniteness of the “wherein” clause set forth in the rejection of the instant claim under 35 USC 112(b) above, and for the sake of compact prosecution, the limitations of the instant claim are being interpreted as limiting the hydrolysate produced by the method. In view of this interpretation, the properties of the protein hydrolysate produced by the method of claim 1 are presumed to inherently result from the functional properties of the enzymes of the proteolytic enzyme mixture of claim 1. As Kikkoman, NCBI4 and Vioque satisfy the structural limitations of the proteolytic enzyme combination as set forth in the rejection of claim 1 above, and as the enzymes of the prior art are substantially identical in structure to enzymes recited in the claims, they are considered to have all of the associated the functional properties according to MPEP 2112.01.I. Therefore one of skill in the art in carrying out the combined method of Kikkoman, NCBI4 and Vioque would necessarily produce a protein hydrolysate characterized by the recited limitations in the instant claim regarding the free glutamic acid concentration and the chromatogram of SEC/CAD.
Regarding claim 49, in view of the indefiniteness of the “wherein” clause set forth in the rejection of the instant claim under 35 USC 112(b) above, and for the sake of compact prosecution, the limitations of the instant claim are being interpreted as limiting the hydrolysate produced by the method. In view of this interpretation, the properties of the protein hydrolysate produced by the method of claim 1 are presumed to inherently result from the functional properties of the enzymes of the proteolytic enzyme mixture of claim 1. As Kikkoman, NCBI4 and Vioque satisfy the structural limitations of the proteolytic enzyme combination as set forth in the rejection of claim 1 above, and as the enzymes of the prior art are substantially identical in structure to enzymes recited in the claims, they are considered to have all of the associated the functional properties according to MPEP 2112.01.I. Therefore one of skill in the art in carrying out the combined method of Kikkoman, NCBI4 and Vioque would necessarily produce a protein hydrolysate characterized by the recited limitations in the instant claim regarding the abundance of peptides bearing an N-terminal XPQQP motif.
Regarding claim 50, in view of the indefiniteness of the “wherein” clause as set forth above, and for the sake of compact prosecution, the claim is being interpreted to require the carrying out of the method claim 1 comprising an exopeptidase and an aminopeptidase, wherein the enzymes are added either simultaneously or sequentially. The method of Kikkoman discussed in the rejection of claim 1 above comprises digesting peptides with three exopeptidases: leucine aminopeptidase, aminopeptidase P, and acidic carboxypeptidase, wherein two of these exopeptidases are aminopeptidases, which is considered to correspond to the contacting of proteases sequentially.
Therefore, the invention of claims 1, 7-9, and 47-50 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 12-19 are newly rejected under 35 U.S.C. 103 as being unpatentable over Kikkoman, NCBI4 and Vioque as applied to claims 1, 7-9, and 47-50 above, and further in view of NCBI2.
The instant rejection is newly stated and necessitated by claim amendment.
Claim 12 is drawn to the method of claim 1, wherein the aminopeptidase comprises a sequence having at least 70% sequence identity to one of SEQ ID NO:10, SEQ ID NO: 11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO: 16, SEQ ID NO: 17 and SEQ ID NO:28 or an aminopeptidase active fragment of a sequence having at least 70% sequence identity to one of SEQ ID NO: 10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17 and SEQ ID NO:28.
The teachings of Kikkoman, NCBI4 and Vioque as applied to claims 1, 7-9, and 47-50 are discussed above. These references do not teach the sequence of the second exopeptidase, which is an aminopeptidase.
Regarding claims 12-19, NCBI2 discloses aminopeptidase Y from Aspergillus clavatus NRRL 1 that shares 100% sequence identity with SEQ ID NO: 10 [see Appendix B], which is considered to correspond to the second exopeptidase, which is an aminopeptidase, as recited in claims.
In view of NCBI2, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Kikkoman and NCBI4 by using the enzyme of NCBI2 as the second exopeptidase, which is an aminopeptidase, to arrive at the claimed invention. One of ordinary skill in the art would have recognized that both the leucine aminopeptidase of Kikkoman and the enzyme of NCBI2 are both aminopeptidase enzymes capable of hydrolyzing protein, and as such both are capable of being incorporated into the method as described by Kikkoman. Thus it would have been obvious to one of ordinary skill in the art to replace the leucine aminopeptidase of Kikkoman with the enzyme aminopeptidase Y of NCBI2, as one of ordinary skill in the art would have been able to carry out such a substitution with reasonable expectation of success because both Kikkoman and NCBI2 relate to aminopeptidase enzymes.
Therefore, the invention of claims 12-19 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 20 is newly rejected under 35 U.S.C. 103 as being unpatentable over Kikkoman, NCBI4, Vioque and NCBI2 as applied to claims 1, 7-9, 12-19, and 47-50 above, and further in view of Merz.
The instant rejection is newly stated and necessitated by claim amendment.
Claim 20 is drawn to the method of claim 19 wherein the proteolytic enzyme mixture further comprises an endopeptidase.
The teachings of Kikkoman, NCBI4, Vioque and NCBI2 as applied to claims 1, 7-9, 12-19, and 47-50 are discussed above. These references do not teach the mixture comprises an endopeptidase.
Merz discusses commercially available peptidase for the production of protein hydrolysates [title], and describes methods for controlling the degree of hydrolysis (DH) of hydrolysates to implement a desired functionality into protein containing foods comprising different peptidase compositions [abstract].
Regarding claim 20, Merz teaches the combination of exopeptidases and endopeptidases in a peptidase preparation mainly influences DH and therefore the peptide composition of the resulting hydrolysate [p 1, col 2, para 2].
In view of Merz, it would have been prima facie obvious one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Kikkoman, NCBI4 and NCBI2 by adding an endopeptidase, as taught by Merz, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Kikkoman, NCBI4 and NCBI2 by using an endopeptidase, because Merz teaches that the combination of exopeptidases and endopeptidases in a peptidase preparation mainly influences DH and therefore the peptide composition of the resulting hydrolysate and its desired functionality. One of ordinary skill in the art would have had a reasonable expectation of success because both Kikkoman and Merz relate to enzymes of producing protein hydrolysates.
Therefore, the invention of claim 20 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 21-27, 29, 32-33 and 43 are newly rejected under 35 U.S.C. 103 as being unpatentable over Kikkoman, NCBI4, Vioque, NCBI2, and Merz as applied to claims 1, 7-9, 12-20, and 47-50 above, and further in view NCBI3.
The instant rejection is newly stated and necessitated by claim amendment.
Claim 21 is drawn to the method of claim 20 wherein the endopeptidase comprises a sequence having at least 70% sequence identity to one of SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25 SEQ ID NO:26, and SEQ ID NO:27 or an endopeptidase active fragment of a sequence having at least 70% sequence identity to one of SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25 SEQ ID NO:26, and SEQ ID NO:27.
The teachings of Kikkoman, NCBI4, Vioque, NCBI2, and Merz as applied to claims 1, 7-9, 12-20, and 47-50 are discussed above. These references do not teach the sequence limitations of the endopeptidase.
Regarding claims 21-27, NCBI3 discloses a peptidase enzyme from Bacillus licheniformis that shares 100% sequence identity with SEQ ID NO: 18 [see Appendix C]. As the sequence is encompassed by the claims, it is therefore presumed to have the recited functional limitations of an endopeptidase (see MPEP 2112.01.I).
In view of NCBI3, it would have been prima facie obvious one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Kikkoman, NCBI4, NCBI2 and Merz by adding the enzyme of NCBI3 to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Kikkoman, NCBI4, NCBI2 and Merz by using the enzyme of NCBI3, because Merz teaches that the combination of different enzymes in a peptidase preparation mainly influences DH and therefore the peptide composition of the resulting hydrolysate and its desired functionality. One of ordinary skill in the art would have had a reasonable expectation of success because Kikkoman, Merz and NCBI3 relate to peptidase enzymes.
Regarding claim 29, Kikkoman discloses during soy sauce production that raw material is decomposed into a polypeptide by a series of proteases [para 0005], wherein the raw material is understood to be proteinaceous material from the soybean vegetable.
Regarding claims 32-33, Kikkoman teaches the subsequent treatment of raw material by a protease, followed by an aminopeptidase and then an acidic carboxypeptidase [para 0005], and Merz teaches methods for controlling the degree of hydrolysis (DH) of hydrolysates to implement a desired functionality into protein containing foods comprising different peptidase compositions [abstract] comprising endopeptidases and exopeptidases [p 1, col 2, para 2]. As Kikkoman teaches one order of applying multiple enzymes to a substrate, and Merz teaches the use of different enzyme combinations to effect different outcomes in hydrolysate characteristics, it would have been obvious for one of skill in the art to try adding the enzymes of the combined method in different orders and in different combinations to arrive at the claimed invention.
Regarding claim 43, Merz teaches the use of protease compositions can be used for wheat gluten hydrolysis [p 2, col 1, para 1].
Therefore, the invention of claims 21-27, 29, 32-33 and 43 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 35 is newly rejected under 35 U.S.C. 103 as being unpatentable over Kikkoman in view of NCBI4, Vioque, NCBI2, Merz and NCBI3 as applied to claims 1, 7-9, 12-27, 29, 32-33, 43, and 47-50 above, and further in view Suzuki et al. (J Agri Food Chem, 2017, 65:10514; cited on the attached Form PTO-892; herein Suzuki).
The instant rejection is newly stated and necessitated by claim amendment.
Claim 35 is drawn to the method of claim 33, wherein the proteolytic enzyme mixture further comprises a glutaminase.
The teachings of NCBI4, Vioque, NCBI2, Merz and NCBI3 as applied to claims 1, 7-9, 12-27, 29, 32-33, 43, and 47-50 are discussed above. These references do not teach a glutaminase.
Suzuki relates to the use production of seasoning from protein hydrolysates using bacterial enzymes [title], and discusses that γ-glutamylation can reduce the bitterness of amino acids and that γ-glutamyl amino acids and γ-glutamyl peptides have a strong kukumi taste that enhances flavor characteristics in food [p 10514, col 2, para 3].
Regarding claim 35, Suzuki teaches the hydrolysis of soy and gluten protein with a protease to produce an initial hydrolysate that is subsequently treated with γ-glutamyltranspeptidase to generate γ-glutamylated protein hydrolysates, wherein γ-glutamyltranspeptidase is a glutaminase [abstract].
In view of Suzuki, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date to modify the combined method of Kikkoman, NCBI4, Vioque, NCBI2, Merz and NCBI3 by adding a glutaminase to the proteolytic enzyme mixture to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Kikkoman, NCBI4, Vioque, NCBI2, Merz and NCBI3 by adding a glutaminase, because Suzuki teaches the treatment of protein hydrolysates produces γ-glutamyl amino acids and γ-glutamyl peptides with a strong kukumi taste that enhances flavor characteristics in food. One of ordinary skill in the art would have had a reasonable expectation of success because Kikkoman and Suzuki relate to the production of protein hydrolysates from vegetable derived protein isolates.
Therefore, the invention of claim 35 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 36-42 are rejected under 35 U.S.C. 103 as being unpatentable over Kikkoman in view of NCBI4, Vioque, NCBI2, Merz, NCBI3 and Suzuki as applied to claims 1, 7-9, 12-27, 29, 32-33, 35, 43 and 47-50 above, and further in view UNI1.
The instant rejection is newly stated and necessitated by claim amendment.
Claim 36 is drawn to the method of claim 35 wherein the glutaminase comprises a sequence having at least 70% sequence identity to SEQ ID NO:29 or a glutaminase active fragment thereof.[AltContent: rect]
The teachings of NCBI4, Vioque, NCBI2, Merz, NCBI3 and Suzuki as applied to claims 1, 7-9, 12-27, 29, 32-33, 35, 43 and 47-50 are discussed above. These references do not teach the sequence limitations of the glutaminase.
Regarding claims 36-42, UNI1 discloses a glutaminase enzyme from Bacillus amyloliquefaciens that shares 100% sequence identity with SEQ ID NO: 29 [see Appendix D].
In view of UNI1, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Kikkoman, NCBI4, NCBI2, Merz, NCBI3 and Suzuki by using the enzyme of UNI1 to arrive at the claimed invention, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the glutaminase of Suzuki and the enzyme of UNI1 are glutaminase enzymes capable of converting glutamine to glutamate, and as such both are capable of being incorporated into the method as described by Kikkoman and Suzuki. Thus it would have been obvious to one of ordinary skill in the art to replace the enzyme of Suzuki with the enzyme of UNI1, as one of ordinary skill in the art would have been able to carry out such a substitution with reasonable expectation of success because both Suzuki and UNI1 relate to glutaminase enzymes.
Therefore, the invention of claims 36-42 would have been obvious to one of ordinary skill in the art before the effective filing date.
Response to Remarks: beginning on page 11 of Applicant’s response to rejections under 35 USC 103; Applicant in summary contends the reliance on the inherency of the enzyme of NCBI4 to presume the activity against XPQQP motifs is legally improper due to variability among EC class 3.4.11.9 enzymes for cleavage of QPQQP of claim 1; Applicant further contends the second exopeptidase recited by the claims distinguishes the second exopeptidase from the first exopeptidase; Applicant further contends Kikkoman’s generic fermentation does not teach targeting XQPPQ bottlenecks characteristic of gluten nor the quantitative outcomes recited in claims 48-49; Applicant further contends there is no teaching or motivation to coordinate the substitution of the leucine aminopeptidase of Kikkoman with the aminopeptidase of NCBI2, as there is no reasonable expectation of success in achieving the same hydrolysate fingerprint or unexpected free glutamic acid increases of claims 12-19; Applicant further contends Merz does not teach the particular three-enzyme choreography that produces the claimed quantitative hydrolysate outcomes of claim 20; Applicant further contends inherency cannot supply claimed performance regarding the rejection of claims 21-27, 29, 32-33, 35 and 43; Applicant further contends the teachings of Kikkoman and Merz do not render the quantitative fingerprint of claims 32-33 predictable; Applicant further contends the art does not teach the combination of glutaminase of UNI1 would yield the unexpected hydrolysate fingerprint and free glutamic acid deltas of claims 48-49.
Applicant’s remarks are considered and found not convincing.
Regarding the assertion that the reliance on the inherency of the enzyme of NCBI4 to presume the activity against XPQQP motifs is legally improper due to variability among EC class 3.4.11.9 enzymes for cleavage of QPQQP of claim 1: As NCBI4 teaches an exopeptidase that is substantially identical in structure with the claimed exopeptidase of SEQ ID NO: 3, it is presumed to have all of the recited functional limitations recited in the claim such as the specificity for peptides having XPQQP motifs, as the function is presumed to be inherent to the sequence (see MPEP 2112.01.I). Regarding the variability for cleavage of QPQQP, it is noted the claims recite peptides with XPQQP, wherein X is understood as any amino acid, and therefore the enzyme of NCBI4 is considered to encompass an enzyme able to cleave QPQQP. Additionally, there are no recited requirements for the cleavage of QPQQP in claim 1 as amended.
Regarding the assertion that the second exopeptidase recited by the claims distinguishes the second exopeptidase from the first exopeptidase: The claims do not recite that the first and the second exopeptidase are different types exopeptidases, and therefore under the broadest reasonable interpretation the claims encompass a method comprising the use of two copies of the same exopeptidase that is an aminopeptidase.
Regarding the assertion that Kikkoman’s generic fermentation does not teach targeting XQPPQ bottlenecks characteristic of gluten nor the quantitative outcomes recited in claims 48-49: The claims do not recite limitations regarding targeting XQPPQ bottlenecks. As stated in the rejection of claims 48-49 above, the properties of the protein hydrolysate produced by the method of claim 1 are considered to result from the functional properties of the enzymes of the proteolytic enzyme mixture of claim 1. As Kikkoman, NCBI4 and Vioque satisfy the structural limitations of the proteolytic enzyme combination as set forth in the rejection of claim 1 above, and as the enzymes of the prior art are substantially identical in structure to enzymes recited in the claims, they are considered to have all of the associated the functional properties according to MPEP 2112.01.I. Therefore one of skill in the art in carrying out the combined method of Kikkoman, NCBI4 and Vioque would be expected to produce a protein hydrolysate characterized by the recited limitations in claims 48-49.
Regarding the assertion that there is no teaching or motivation to coordinate the substitution of the leucine aminopeptidase of Kikkoman with the aminopeptidase of NCBI2, as there is no reasonable expectation of success in achieving the same hydrolysate fingerprint or unexpected free glutamic acid increases of claims 12-19; The simple substitution rationale for obviousness does not require a teaching to substitute, but instead requires a recognition by one of ordinary skill in the art that the substituted component and its functions were known in the art, and that one of skill in the art could have substituted one element for another with a reasonable expectation of success. As the leucine aminopeptidase of Kikkoman and the enzyme of NCBI2 are both aminopeptidase enzymes capable of hydrolyzing protein, both are therefore capable of being incorporated into the method as described by Kikkoman. Thus it would have been obvious to one of ordinary skill in the art to replace the leucine aminopeptidase of Kikkoman with the enzyme aminopeptidase Y of NCBI2, as one of ordinary skill in the art would have been able to carry out such a substitution with reasonable expectation of success because both Kikkoman and NCBI2 relate to aminopeptidase enzymes. As amended, claims 12-19 do not recite any required hydrolysate fingerprint or unexpected free glutamic acid increases.
Regarding the assertion that Merz does not teach the particular three-enzyme choreography that produces the claimed quantitative hydrolysate outcomes of claim 20; Claim 20 does not recite any quantitative hydrolysate outcomes.
Regarding the assertion that inherency cannot supply claimed performance regarding the rejection of claims 21-27, 29, 32-33, 35 and 43; Claims 21-27, 29, 32-33, 35 and 43 do not recite any performance limitations. Considering the interpretation that Applicant is stating inherency cannot supply claimed functional limitations regarding, for example, the target sequences for proteolytic cleavage, according to MPEP 2112.01.I, as the enzymes of the prior art are substantially identical in structure to enzymes recited in the claims, they are considered to have all of the associated the functional properties, as the functional properties are presumed to be inherent to the structures of the enzymes.
Regarding the assertion that the teachings of Kikkoman and Merz do not render the quantitative fingerprint of claims 32-33 predictable; Claims 32-33 do not recite any limitations regarding quantitative fingerprints.
Regarding the assertion the art does not teach the combination of glutaminase of UNI1 would yield the unexpected hydrolysate fingerprint and free glutamic acid deltas of claims 48-49; Claims 48-49 do not require the inclusion of the glutaminase of claims 36-42 as asserted by Applicant, and claims 36-42 do not recite limitations of unexpected hydrolysate fingerprint and free glutamic acid deltas.
Applicant’s statements regarding the unexpected hydrolysate fingerprint and free glutamic acid deltas is being interpreted as an allegation of unexpected results to rebut the prima facie obviousness of the claims.
According to MPEP 716.02(a), Evidence must show unexpected results. As Applicant has shown no evidence of unexpected results and merely states the results of the claimed method are unexpected, Applicant’s allegation of unexpected results does not satisfy the requirements of MPEP 716.02(a).
According to MPEP 716.02(b)(II), Applicants have the burden of explaining proffered data. As Applicant has not proffered data to support the alleged unexpected results, Applicant’s allegation of unexpected results does not satisfy the requirements of MPEP 716.02(b)(II).
According to MPEP 716.02(e), Applicants must compare unexpected results with the closest prior art. As applicant has not provided any evidence or data to establish unexpected results, Applicant has therefore not compared said unexpected results with the closest prior art. Therefore, Applicant’s allegation of unexpected results does not satisfy the requirements of MPEP 716.02(e).
According to MPEP 716.02(d), Unexpected results must be commensurate in scope with the claimed invention. As the scope of the claims does encompass a protein hydrolysate with any specific hydrolysate fingerprint or free glutamic acid deltas, Applicant’s allegations of unexpected results are considered to be not commensurate in scope with the claimed invention. Therefore, Applicant’s allegation of unexpected results does not satisfy the requirements of MPEP 716.02(d).
For these reasons, Applicant’s allegation of unexpected results is considered insufficient to rebut a prima facie case of obviousness.
In response to applicant’s argument that the examiner’s conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant’s disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Conclusion
Status of the Application:
Claims 1, 7-9, 12-27, 29, 32-33, 35-43 and 47-50 are pending.
Claims 1, 7-9, 12-27, 29, 32-33, 35-43 and 47-50 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH SPANGLER whose telephone number is (571)270-0314. The examiner can normally be reached M-F 7:30 am - 4:30 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, Manjunath Rao can be reached at (571) 272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH R SPANGLER/
Examiner
Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656
Appendix A
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401
642
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Greyscale
Sequence alignment of SEQ ID NO: 3 with NCBI Accession No. XP_024745139.1 (reference NCBI4)
Appendix B
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394
641
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Greyscale
Sequence alignment of SEQ ID NO: 10 with NCBI Accession No. EAW12353.1 (reference NCBI2)
Appendix C
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400
642
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Greyscale
Sequence alignment of SEQ ID NO: 18 with NCBI Accession No. AFT92040.1 (reference NCBI3)
Appendix D
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741
1008
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Greyscale
Sequence alignment of SEQ ID NO: 29 with UniProt Accession No. A0A1Y0XA48_BACAM (reference UNI1)