DETAILED OFFICE ACTION
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 .
Claims 1-6 are pending and are being examined on the merits.
Applicant’s amendment to the specification, filed January 15, 2024, is acknowledged.
Priority
This application is filed as CON of PCT/CN2023/111378, filed on August 7, 2023, which claims foreign priority under 35 U.S.C. 119(a)-(d) to a foreign patent application CN202211127625.5 filed on September 16, 2022. No certified copy of the foreign priority application has been filed in this application so the effective filing date for this application is August 7, 2023.
Claim Objections
Claims 1, 5, and 6 are objected to because of the recitation of the abbreviation “MmPI” without first writing out the full phrase for which the abbreviation “MmPI” is used. Applicant may consider amending the first occurrence of “MmPI” in claim 1 to recite “Matrix metalloproteinase inhibitor (MmPI).”
Claims 1-2 and 5 are objected to for reciting “SEQ ID NO.” According to MPEP 608.01(m), “Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995)”. In the interest of improving claim form, the Office suggests amending “SEQ ID NO.” to ““SEQ ID NO:”.
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.
Claims 1 and 5-6 are 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.
Claim 1 is rejected as indefinite for reciting the phase “an effective amount of an MmPI.” The phrase “an effective amount” may be held as indefinite when the claim fails to state the function which is to be achieved (see MPEP 2173.05(c)). It is suggested that applicant clarify the meaning of the term “effective amount” or remove the phrase.
Claim 5 is rejected as indefinite for reciting a method without reciting any active, positive step(s) delimiting how to practice the method. It is suggested that applicant amend the claim to provide active, positive step(s) for practicing the method.
Claim 6 is rejected as indefinite for reciting “the MmPI of claim 1.” Claim 1 is drawn to a method of preparing trypsin inhibitors, not an MmPI. Therefore, it is unclear as to whether or not the method of claim 6 requires the step(s) of claim 1.
Claim Interpretation
Claim 1 is interpreted as “A method of preparing trypsin inhibitors, comprising adding a protein comprising an amino acid sequence with at least two or more contiguous amino acids of SEQ ID NO: 1 to a preparation of protease inhibitors.”
Claim 2 is interpreted as “A nucleotide sequence, wherein a nucleotide sequence of the nucleic acid with is at least two or more contiguous nucleic acids of SEQ ID NO: 2.
Claim 3 is interpreted as “A plasmid carrying the nucleic acid of claim 2.”
Claim 4 is interpreted as “A host expression strain carrying the plasmid of claim 3.”
Claim 5 is interpreted as “A method of expressing a product of the strain of claim 4, wherein the expression product is an amino acid sequence with at least two or more contiguous amino acids of SEQ ID NO: 1.”
Claim 6 is interpreted as “A method of eliminating activity of a protein comprising an amino acid sequence with at least two or more contiguous amino acids of SEQ ID NO: 1 of claim 1, comprising: placing the protein comprising an amino acid sequence with at least two or more contiguous amino acids of SEQ ID NO: 1 in an environment of 121°C and 0.21 MPa for 20 minutes; or, eliminating the protein comprising an amino acid sequence with at least two or more contiguous amino acids of SEQ ID NO: 1 by Maillard reaction mediated by reducing sugar.”
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.
Claims 1-6 are rejected under 35 U.S.C. 112(a) 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 at the time the application was filed, had possession of the claimed invention.
MPEP 2163.II.A.2.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
According to MPEP 2163.II.A.3.(a).ii), [s]atisfactory 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 factors considered in the Written Description requirement are (1) level of skill and knowledge in the art, (2) partial structure, (3) physical and/or chemical properties, (4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the (5) method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP § 2163.
Claim 1 (claim 6 dependent therefrom) is drawn to a method of preparing trypsin inhibitors comprising a genus of MmPIs comprising any two or more contiguous amino acids of SEQ ID NO: 1.
Given a broadest reasonable interpretation, the remaining sequence of the MmPI is unlimited and encompass any amino acid insertions, deletions, and substitutions relative to SEQ ID NO: 1, and the function of the genus of MmPI is unlimited and encompass, e.g., non-functional proteins or proteins with any function. As such, the recited genus of MmPIs is considered to encompass widely variant species.
The specification discloses the following representative species of the genus of recited MmPI amino acid sequences: MmPI comprising the amino acid sequence of SEQ ID NO: 1.
Claim 2 (claims 3-5 dependent therefrom) is drawn to a genus of isolated gene fragments comprising at least two or more contiguous nucleotides of SEQ ID NO: 2.
Given a broadest reasonable interpretation, the remaining sequence of the nucleic acid sequence is unlimited and encompass any nucleic insertions, deletions, and substitutions relative to SEQ ID NO: 2. As such, the recited genus of gene fragments is considered to encompass widely variant species.
The specification discloses the following representative species of the genus of gene fragments: MmPI nucleic acid sequence comprising the nucleotide sequence of SEQ ID NO: 2.
Claim 5 is drawn to a method of expressing a product of the strain of claim 4, wherein the expression product is a genus of MmPIs with at least two or more contiguous amino acids of SEQ ID NO: 1.
Given a broadest reasonable interpretation, the remaining sequence of the MmPI is unlimited and encompass any amino acid insertions, deletions, and substitutions relative to SEQ ID NO: 1, and the function of the genus of MmPI is unlimited and encompass, e.g., non-functional proteins or proteins with any function. As such, the recited genus of MmPIs is considered to encompass widely variant species.
The specification discloses the following representative species of the genus of recited MmPI amino acid sequences: MmPI comprising the amino acid sequence of SEQ ID NO: 1.
Regarding the level of skill and knowledge in the art of amino acid mutation, the reference of Singh et al. (Curr. Protein Pept. Sci. 18:1-11, 2017) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see p. 7, column 1, top). Also, the unpredictability associated with amino acid mutations is exemplified by the reference of Zhang et al. (Structure 26:1474-1485, 2018) which discloses that even a mutation of a surface residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide (p. 1475, column 1).
In view of the widely variant genera of MmPIs and gene fragments, the high level of unpredictability in the art of amino acid mutations, and only a single representative species of MmPIs and gene fragments is disclosed, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genera, and thus, that the applicant was not in possession of the recited genera. The claimed subject matter is not supported by an adequate written description because a representative number of species has not been described.
Claims 1-6 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for an MmPI with the amino acid sequence of SEQ ID NO: 1 as well as a polynucleotide with the nucleic acid sequence of SEQ ID NO: 2, does not reasonably provide enablement for all MmPI amino acid sequences and nucleic acids encoding thereof encompassed by the claims, particularly with respect to the scope of recited MmPIs and gene fragments.
“The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.” In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)) as follows: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a). The Factors considered to be most relevant to the instant rejection are addressed in detail below.
The nature of the invention: The nature of the invention a method of preparing trypsin inhibitors comprising MmPI.
The breadth of the claims: Claim 1 (claim 6 dependent therefrom) is drawn to a method of preparing trypsin inhibitors comprising a MmPI comprising any two or more contiguous amino acids of SEQ ID NO: 1.
Given a broadest reasonable interpretation, the remaining sequence of the MmPI is unlimited and encompass any amino acid insertions, deletions, and substitutions relative to SEQ ID NO: 1, and the function of the MmPI is unlimited and encompass, e.g., non-functional proteins or proteins with any function.
Claim 2 (claims 3-5 dependent therefrom) is drawn to an isolated gene fragment comprising at least two or more contiguous nucleotides of SEQ ID NO: 2.
Given a broadest reasonable interpretation, the remaining sequence of the nucleic acid sequence is unlimited and encompass any nucleic insertions, deletions, and substitutions relative to SEQ ID NO: 2.
Claim 5 is drawn to a method of expressing a product of the strain of claim 4, wherein the expression product is a MmPI with at least two or more contiguous amino acids of SEQ ID NO: 1.
Given a broadest reasonable interpretation, the remaining sequence of the MmPI is unlimited and encompass any amino acid insertions, deletions, and substitutions relative to SEQ ID NO: 1, and the function of the MmPI is unlimited and encompass, e.g., non-functional proteins or proteins with any function.
The state of the prior art; The level of one of ordinary skill; and The level of predictability in the art: According to MPEP 2164.03, “…what is known in the art provides evidence as to the question of predictability” and “[I]f one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art.”
The reference of Singh et al. (Curr. Protein Pept. Sci. 18:1-11, 2017) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see p. 7, column 1, top).
The unpredictability associated with amino acid mutation is exemplified by the reference of Zhang et al. (Structure 26:1474-1485, 2018), which discloses that even a mutation that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide (p. 1475, column 1).
As such, one of skill in the art would recognize a high level of unpredictability that all recited MmPI amino acid sequences and gene fragments encoding thereof encompassed by the claims would maintain the desired activity/utility.
The amount of direction provided by the inventor and The existence of working examples: The specification discloses the following working example of the recited MmPI amino acid sequences: MmPI with the amino acid sequence of SEQ ID NO: 1.
The specification discloses the following working example of gene fragments: a polynucleotide comprising the nucleic acid sequence of SEQ ID NO: 2.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure: While methods of modifying the amino acid sequence of a polypeptide and the nucleotide sequence of a polynucleotide were known at the time of the invention, it was not routine in the art to make all MmPIs and gene fragments as broadly encompassed by the claims.
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, and the state of the prior art, undue experimentation would be necessary for a skilled artisan to make and use the entire scope of the claimed invention. Applicants have not provided sufficient guidance to enable one of 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 having the desired biological characteristics is 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 § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 2-4 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Applicant’s attention is directed to the "Guidance for Determining Subject Matter Eligibility Of Claims Reciting Or Involving Laws of Nature, Natural Phenomena, & Natural Products”, released on December 16, 2014.
Claim Interpretation: Given a broadest reasonable interpretation, claim 2 reads on a polynucleotide encoding a protease and trypsin inhibitor from a mulberry (Morus notabilis) taught by EXB81311 with a plurality of two or more contiguous nucleic acids of the instant SEQ ID NO: 2 (p. 1; see sequence alignment below).
PNG
media_image1.png
297
580
media_image1.png
Greyscale
Given a broadest reasonable interpretation, claims 2-4 read on an Escherichia coli comprising the naturally occurring RSF1010 plasmid taught by Scholz et al. (Gene, published 1989, Vol. 75, No. 2, p. 271-288; cited on the attached Form PTO-892; hereafter “Scholz”) which comprises the gene sequence encoding protein H with at least two contiguous nucleotides polynucleotide of instant SEQ ID NO: 2 (Abstract; Figure 1, see sequence alignment below).
PNG
media_image2.png
171
577
media_image2.png
Greyscale
Patent Eligibility Analysis Step 1: The claims are drawn to a composition of matter or a process, which is one of the statutory categories of invention.
Patent Eligibility Analysis Step 2A Prong 1: The claims recite a naturally occurring polypeptide, polynucleotide, and method, which are considered to be laws of nature or a natural phenomena (a natural product or process). Accordingly, the claims are directed to judicial exceptions.
Patent Eligibility Analysis Step 2A Prong 2: There are no additional elements recited in the claims beyond the judicial exceptions.
Patent Eligibility Analysis Step 2B: The claims only recite the product of nature and do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims do not provide any additional element different from their natural counterparts.
For these reasons, the claims are rejected under section 101 as being directed to non-statutory subject matter.
Claim 5 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
Claim 5 is drawn to a method of expressing a product of the strain of claim 4, wherein the expression product is MmPI with an amino acid sequence as shown in SEQ ID NO: 1. Claim 5 does not fall within at least one of the four categories of patent eligible subject matter because the claims fail to recite any active, positive steps detailing how strain of claim 4 is to be utilized to produce an expression product of MmPI with an amino acid sequence as shown in SEQ ID NO: 1.
Claim Rejections - 35 USC § 102
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.
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 (i.e., changing from AIA to pre-AIA ) 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.
Claims 2-4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Scholz.
Scholz teaches am Escherichia coli comprising the naturally occurring RSF1010 plasmid which comprises the gene sequence encoding protein H with at least two contiguous nucleotides polynucleotide of instant SEQ ID NO: 2 (Abstract; Figure 1, see sequence alignment below).
PNG
media_image2.png
171
577
media_image2.png
Greyscale
For the reasons stated herein, claims 2-4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Scholz.
Claims 2 and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by European Molecular Biology Laboratory Identifier EXB81311 (version 3, published April 30, 2014; cited on the attached Form PTO-892; hereafter “EXB81311”) as evidenced by W9RJZ5.
Regarding claim 2, EXB81311 teaches a protease and trypsin inhibitor from a mulberry (Morus notabilis) with a plurality of has a plurality of two or more contiguous nucleic acids of the instant SEQ ID NO: 2 (p. 1; see sequence alignment below).
PNG
media_image1.png
297
580
media_image1.png
Greyscale
Regarding claim 5, W9RJZ5 is cited in accordance with MPEP 2131.01.III to the protease/trypsin inhibitor is associated with the EMBL identifier EXB81311.1 (p. 1). W9RJZ5 teaches mulberry tree (Morus notabilis) produces a protease inhibitor that is also a trypsin inhibitor, which has a plurality of two or more contiguous amino acids of the instant SEQ ID NO: 1 (p. 1; see sequence alignment below)
PNG
media_image3.png
244
620
media_image3.png
Greyscale
Therefore, an ordinary artisan would immediately recognize Morus notabilis comprises the nucleotide sequence taught by EXB81311 and produces the amino acid taught by W9RJZ5.
For the reasons stated herein, claims 2 and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by EXB81311 and as evidenced by W9RJZ5.
Claims 2-5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hawkins (US 5,643,752; cited on the attached Form PTO-892; hereafter “Hawkins”).
Regarding claims 2-4, Hawkins teaches a host transformed with a plasmid comprising the acid sequence of TIMP-4 with at least two or more contiguous nucleotides from instant SEQ ID NO: 2 (col 10, para 7 - col 11, para 1; Claims 3-5; Figure 1; SEQ ID NO: 1, see sequence alignment below).
PNG
media_image4.png
107
591
media_image4.png
Greyscale
Hawkins teaches TIMP-4 inhibits matrix metalloproteins (MMPs) (col 3, para 5; col 4, para 2-3).
Regarding claim 5, Hawkins teaches a method producing a TIMP-4 polypeptide with an amino acid sequence comprising at least two contiguous amino acids of instant SEQ ID NO: 1, wherein the method comprises culturing the transformed host cell to allow expression of the polypeptide (Claim 6; Figure 1; SEQ ID NO: 2, see alignment below).
PNG
media_image5.png
64
174
media_image5.png
Greyscale
For the reasons stated herein, claims 2 and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hawkins.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over UniProt W9RJZ5 in view of Thermo Scientific™ (Pierce Protease Inhibitor Tablets , Catalog number A32963, ThermoFisher, available May 7, 2021; cited on the attached Form PTO-892; hereafter “Thermo”), and as evidenced by Roche Molecular Biochemicals (The Complete Guide for Protease Inhibition, available on November 22, 2015; cited on the attached Form PTO-892; hereafter “Roche”).
Regarding claim 1, W9RJZ5 teaches a protease inhibitor that is also a trypsin inhibitor from a mulberry tree (Morus notabilis) that has a plurality of two or more contiguous amino acids of the instant SEQ ID NO: 1 (p. 1; see sequence alignment below).
PNG
media_image3.png
244
620
media_image3.png
Greyscale
W9RJZ5 does not explicitly teach adding a protein comprising an amino acid sequence with at least two or more contiguous amino acids of SEQ ID NO: 1 to a preparation of protease inhibitors that reside outside a mulberry tree.
Thermo teaches Pierce Protease Inhibitor Tablets contain AEBSF, aprotinin, bestatin, E-64, leupeptin, and pepstatin A (p. 1, paragraph beginning “Pierce Protease Inhibitor Tablets protect”). Thermo teaches dissolving Pierce Protease Inhibitor Tablets in buffer or lysate to use the product (p. 1, paragraph beginning “To use Pierce Protease Inhibitor Tablets”).
Evidentiary reference Roche is cited to show AEBSF, aprotinin, and leupeptin inhibit trypsin (Table on p. 6, Table on p. 7) as well as that AEBSF, aprotinin, bestatin, E-64, leupeptin, and pepstatin are protease inhibitors (Table on top of p. 5; Table on p. 6; Table on p. 7). Therefore, the Pierce Protease Inhibitor Tablets taught by Thermo inherently comprises a plurality of trypsin inhibitors and protease inhibitors.
In view of the combined teachings of W9RJZ5 and Thermo, it would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to add the trypsin inhibitor taught by W9RJZ5 to a solution comprising dissolved Pierce Protease Inhibitor Tablets taught by Thermo, thereby arriving at the invention of claim 1.
An ordinary artisan would have been motivated to and would have had a reasonable expectation of success of adding the protease and trypsin inhibitor taught by W9RJZ5 to a solution of comprising dissolved Pierce Protease Inhibitor Tablets taught by Thermo. This is because “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). See MPEP 2144.06.I. Since W9RJZ5 taught a protease and trypsin inhibitor and a solution of dissolved Pierce Protease Inhibitor Tablets from Thermo comprises protease and trypsin inhibitors, it is obvious to combine the two components with each other since they are useful for the same purpose of inhibiting proteases.
Consequently, the invention of claim 1 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over EXB81311 in view of W9RJZ5, Liang et al. (Front. Plant Sci., published April 15, 2020, Vol . 11, No. 419; cited on the attached Form PTO-892; hereafter “Liang”), and Thermo, and as evidenced by Roche.
The relevant teachings of EXB81311 and evidentiary reference W9RJZ5 as applied to claims 2 and 5 are discussed above and incorporated herein.
The relevant teachings of W9RJZ5, Thermo, and evidentiary reference Roche as applied to claim 1 are discussed above and incorporated herein.
Regarding claims 3-4, the teachings of EXB81311 do not explicitly teach a plasmid that comprises at least two or more contiguous nucleotides in SEQ ID NO. 2 nor a host expression strain carrying the plasmid.
W9RJZ5 further teaches the protease/trypsin inhibitor is associated with the EMBL identifier EXB81311.1 (p. 1). An ordinary artisan would have immediately envisioned the EMBL identifier represents the nucleic acid encoding W9RJZ5.
Liang teaches a method of producing recombinant proteins from a mulberry (Morus notabilis) comprising introducing the plasmid into Escherichia coli BL21 bacteria, and expressing and harvesting the recombinant proteins from the bacteria (p. 1141, col 1, para 1; p. 1142, col 1, para 2; ).
In view of the combined teachings of EXB81311, W9RJZ5, Liang, and Thermo, it would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to insert the nucleic acid taught by EXB81311, which encodes the amino acid taught by W9RJZ5, into a plasmid in order to incorporate the plasmid into Escherichia coli, express, and harvest the recombinant expression product via the method taught by Liang, thereby arriving at the invention of claims 3-4.
An ordinary artisan would have been motivated to and would have had a reasonable expectation of success of inserting the nucleic acid taught by EXB81311, which encodes the amino acid taught by W9RJZ5, into a plasmid in order to incorporate the plasmid into Escherichia coli, express, and harvest the recombinant expression product via the method taught by Liang. This is because Liang taught a method of producing recombinant proteins from a mulberry (Morus notabilis) comprising introducing the plasmid into Escherichia coli bacteria, and expressing and harvesting the recombinant proteins from the bacteria. An ordinary artisan would also have been motivated to using the isolated the recombinant expression of W9RJZ5 from the Escherichia coli BL21 bacteria in order to inhibit proteinases/trypsin with the proteinase/trypsin inhibitor protein taught by W9RJZ5 in a solution of Pierce Protease Inhibitor Tablets taught by Thermo.
Consequently, the invention of claims 3-4 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over W9RJZ5 in view of Thermo and as evidenced by Roch as applied to claim 1 above, and further in view of CN113785933A (published December 14, 2021; cited on the attached Form PTO-892). Reference is made to a machine translation of CN113785933A obtained from Espacenet; cited on the attached Form PTO-892; hereafter “CN’933”).
The relevant teachings of W9RJZ5, Thermo, and evidentiary reference Roche as applied to claim 1 are discussed above and incorporated herein.
Regarding claim 6, W9RJZ5 further teaches the protease/trypsin inhibitor is also a serine protease inhibitor (p. 1).
The combined teachings of W9RJZ5 and Thermo does not explicitly teach eliminating the activity of a protein comprising an amino acid sequence with at least two or more contiguous amino acids of SEQ ID NO: 1 by placement in an environment of 121°C and 0.21 MPa for 20 minutes or via Maillard reaction mediated by reducing sugar.
CN’933 teaches eliminating the activity of a trypsin inhibitor or serine protease inhibitor from mulberry leaves through a treatment at 21° C. and 0.21 MPa for 20 minutes (Abstract; p. 2, paragraph beginning “Morus is a deciduous tree”; p. 3, para 1-8; p. 3, para 17).
In view of the combined teachings of W9RJZ5, Thermo, and CN’933, it would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to eliminate the activity of the mulberry trypsin inhibitor and serine protease inhibitor proteins taught by W9RJZ5 via the method taught by CN’933 comprising a treatment at 21° C. and 0.21 MPa for 20 minutes, thereby arriving at the invention of claim 6.
An ordinary artisan would have been motivated to and would have had a reasonable expectation of success of eliminating the activity of the mulberry trypsin inhibitor and serine protease inhibitor proteins taught by W9RJZ5 via the method taught by CN’933 comprising a treatment at 21° C and 0.21 MPa for 20 minutes. This is because the mulberry protein taught by W9RJZ5 is a trypsin inhibitor and serine protease inhibitor, and CN’933 taught eliminating the activity of a trypsin inhibitor or serine protease inhibitor from mulberry leaves through a treatment at 21° C. and 0.21 MPa for 20 minutes.
Consequently, the invention of claim 6 would have been obvious to one of ordinary skill in the art before the effective filing date.
Conclusion
No claims are currently allowed for the reasons as stated above. Applicants must
respond to the objections/rejections in this Office action to be fully responsive in
prosecution.
The instant Office Action is non-final.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SCOTT E. MULDER whose telephone number is (571)272-2372. The examiner can normally be reached Monday - Friday 7:30 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, Manjunath Rao can be reached on (571) 272-0939. 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.
/SCOTT E. MULDER/Examiner, Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656