DETAILED ACTION
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 .
Application Status
This action is written in response to claims received on June 01, 2023. Claims 1-10 are currently pending and under consideration.
Priority
Claims 1-15 are granted priority to the International Patent Application PCT//CN2022/115683 filed on August 30, 2022.
Information Disclosure Statement
To date, no Information Disclosure Statement has been filed. Applicant is reminded of the duty to disclose.
The listing of references in the specification (pg. 1, line 8) is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete.
The incorporation by reference paragraph is missing from the specification received on Mar 16, 2026. In addition, a certified copy of English translation of PCT//CN2022/115683 is not provided to determine whether this incorporation by reference paragraph is included.
Required response - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because of the following informalities: The word “efficienc” on pg. 5, line 17, is misspelled. A period is also missing for the last sentence on the last paragraph of pg. 15.
Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities:
For clarity and precision of claim language, it is suggested that claim is amended to read, “A molecular peptide mutant, wherein the peptide consists of or comprises the amino acid sequence set forth in SEQ ID NO: 1 and, wherein the molecular peptide mutant forms ester bonds.” Please see section 112(b) regarding claim indefinites for emphasized part.
Appropriate action is required.
Claim 4 is objected to because of the following informalities:
Claim 4 recites “IPTG” without previous recitation of isopropyl β-D-1-thiogalactopyranoside. The full name must be recited upon first mention, followed by the acronym in parenthesis.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, and 4-10 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 term “high”, which is a relative term which renders the claim indefinite. The term “high” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear to what degree an ester bond formation efficiency is considered high, regular, or low.
Claim 1 recites “wherein the amino acid sequence is as shown in SEQ ID NO:1”, which renders the determination of the exact scope of the claim difficult. It is unclear whether the molecular peptide mutant consists of or comprises the amino acid sequence set forth in SEQ ID NO: 1. It is unclear whether claim 1 includes a molecular peptide mutant that contains SEQ ID NO:1 and additional unclaimed sequences or claim 1 includes a molecular peptide mutant that is exactly SEQ ID NO:1 with no additional sequences.
Claim 4 recites the limitation "the gene sequence" in line 3. There is insufficient antecedent basis for this limitation in the claim. It is noted the first recitation of “gene sequence” is in claim 2. It is unclear how the gene sequence is 4 is related to claim 2. Claim 4 also recites the limitation “the molecular peptide” in line 3. There is insufficient antecedent basis for this limitation in the claim. It is noted claim 4, line 1, recites “molecular peptide mutant”. It is unclear how the requirement of mutant in line 1 is related to the molecular peptide in line 3. It is unclear whether the molecular peptide in line 3 is required to be a mutant or not. Claim 4 also recites the limitations “the crushed liquid” and “the supernatant” in line 11. There is insufficient antecedent basis for these two limitations in the claim.
Claim 6 recites the limitation “the restriction enzyme sites” line 1. There is insufficient antecedent basis for this limitation in the claim. There is no recitation of restriction enzyme sites in any other claims.
Claim 8 recites the limitation “in the (2), E. coli BL21” in line 1. It is noted that step (2) recites a host bacterium and claim 7 further limits the host bacterium to be E. coli BL21. However, claim 8 depends on claim 4 which does not recite wherein the host bacterium is E. coli BL21. Accordingly, there is insufficient antecedent basis for the limitation E. coli BL21 in step (2). It is also unclear how the requirement of E. coli BL21 in claim 7 is related to claim 8.
Those claims included in the statement of rejection but not otherwise discussed are rejected for depending from a rejected claim but failing to remedy the indefiniteness therein.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 3 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. Claim 3 does not fall within at least one of the four categories of patent eligible subject matter because it recites “an application of the molecular peptide mutant”, which is NOT one of the four categories of subject matter that Congress deemed to be appropriate subject matter for a patent: processes, machines, manufactures and compositions of matter (Step 1 of Subject Eligibility Analysis: NO) (see MPEP 2106.03 (I) and (II)). As explained by the courts, these "four categories together describe the exclusive reach of patentable subject matter. If a claim covers material not found in any of the four statutory categories, that claim falls outside the plainly expressed scope of § 101 even if the subject matter is otherwise new and useful." In re Nuijten, 500 F.3d 1346, 1354, 84 USPQ2d 1495, 1500 (Fed. Cir. 2007).
Claim Rejections - 35 USC § 112
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 2 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP 2163.II.A.3.(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”.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. Claim 1 is directed to a peptide mutant with a high ester bond formation efficiency, and the peptide mutant has an amino acid sequence set forth in SEQ ID NO: 1. Under the broadest reasonable interpretation, claim 1 is interpreted as requiring that the recited peptide mutant exhibits ester bond formation efficiency greater than that of the corresponding wild-type peptide. Sequence alignment of SEQ ID NO:1 (shown below) demonstrates that the wild-type peptide is Cpe0147 from Clostridium perfringens (EDT23863.1; putative surface anchored protein [Clostridium perfringens B str. ATCC 3626], BioCollection Taxonomy Date: March 24, 2008). Further, Claim 2 is merely directed to a gene sequence encoding the peptide mutant, without reciting additional limitations to the peptide mutant.
PNG
media_image1.png
198
665
media_image1.png
Greyscale
The specification discloses that SEQ ID NO:1 differs from wild-type peptide, referred as Catcher, by three mutations Y, I, and E (FIG. 1) and asserts that these mutations improve stability of the peptide mutant in water solution without affecting the structure (pg. 3, lines 5-16; Embodiment 1). Therefore, the specification asserts a correlation between structure and function. However, none of these mutations are characterized with respect to ester bond formation activity or efficiency. The specification fails to provide any experimental data, structural analysis, or mechanistic explanation demonstrating that peptide mutant of SEQ ID NO:1 exhibits a high ester bond formation efficiency as claimed
It is noted that the specification discloses that peptide mutant of SEQ ID NO:1 “has the ability to form an isopeptide bond with EBTag and also significantly increases the covalent bond formation efficiency (pg. 5, lines 13-14). However, isopeptide bond formation is mechanistically distinct from ester bond formation, and the specification does not establish any connection, correlation, or nexus between these two activities. The mere disclosure of isopeptide bond formation does not reasonably convey possession of a peptide having a high ester bond formation efficiency as claimed. Further, knowledge of one function activity does not demonstrate possession of a different, mechanistically distinct activity.
The state of the art establishes that wild-type peptide forms ester bonds via conserved residues within a defined catalytic environment. In addition, Kwon et al (Autocatalytically generated Thr-Gln ester bond cross-links stabilize the repetitive Ig-domain shaft of a bacterial cell surface adhesin; PNAS, 2014, 11(4):1367-1372) teaches a putative cell-surface adhesin from Clostridium perfringens (Cpe0147) has an adhesin domain and 11 repeat domains (Fig. 1), and analysis of bond geometry and interatomic contacts revealed suggests ester bond formation between Thr and Gln in a single putative domain construct (C1), which aligns with claimed peptide mutant of SEQ ID NO: 1 without mutations. Kwon et al further teaches key residues for ester bond formation involving threonine, histidine, glutamic acid and glutamine at specific positions. Further, Squire et al (WO 2018/093274 A1; Published Date: May 24, 2018) teaches a binding partner comprising amino acids 439-563 of Cpe0147 from C. perfringens spontaneously forms one or more ester bonds with a peptide tag comprising amino acids 565-587 also of Cpe0147 from C. perfringens ([0023], [0025], [0026], and [0028]). Squire et al further teaches wherein “one of the amino acids is a reactive residue capable of spontaneously forming an intermolecular ester bond” selected from the group comprising threonine, serine, glutamine, and glutamic acid ([0028]). Given that the three mutations introduced in SEQ ID NO:1 are outside of the key residues taught by Kwon and Squire, the prior art provides a reasonable basis to expect that SEQ ID NO:1 may retain ester bond formation capability.
However, the prior art does not teach or suggest that mutations introduced in SEQ ID NO:1 would result in high ester bond formation efficiency. In view of the unpredictability of protein structure and function relationships, especially for covalent bond formation activity, the specification does not provide guidance enabling a skilled artisan to recognize or predict that SEQ ID NO:1 exhibits a high ester bond formation efficiency.
Based on the preponderance of the evidence, including the relevant teachings of the specification, the absence of working examples, and the state of the art including knowledge of key residues involved in Cpe0147 ester bond formation, one skilled in the art would conclude that Applicant was not in possession of a peptide mutant of SEQ ID NO:1 with a high ester bond formation efficiency.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (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.
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.
Claims 4, 7, and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yosaatmadja (Ester bond formation in bacterial adhesins; Thesis, University of Auckland Research Repository, August 2018).
Regarding claims 4, 7, and 9, Yosaatmadja teaches a method for purifying Cpe0147 from Clostridium perfringens (i.e., wild type of instant peptide mutant of SEQ ID NO:1) comprising the following steps:
Amplifying the gene sequence of Cpe0147 using polymerase chain reaction (pg. 42, section 2.5.2 PCR), performing restriction endonuclease digestion (pg. 46, section 2.5.6 Restriction endonuclease digestion), ligating DNA fragments that are products of the digestion (pg. 47, section 2.5.7 DNA ligation for cloning) to construct a recombinant plasmid, introducing the recombinant plasmid into a host bacterium E. coli BL21 (DE3) via transformation (pg. 48, section 2.5.9 DNA transformation).
Culturing E. coli BL21 (DE3) cells containing the recombinant plasmid until OD600 reaches 0.7-1.0 (within claimed range of 0.6-0.8) and adding IPTG for induction (pg. 49, section 2.6 Recombinant protein expression and subsection 2.6.1 Small scale protein expression)
Centrifuging the culture after induction, collecting the cells (pg. 49, section 2.6.1 Small scale protein expression), resuspending pellet in lysis IMAC buffer (i.e., phosphate buffer solution) (pg. 50, section 2.7.2 Large scale protein purification, and table 2.12), and proceeding with ultrasonication (pg. 51, section 2.7.2 Large scale protein purification)
Centrifuging lysate from insoluble material and cellular debris, filtering lysate, and loading onto an immobilized metal affinity chromatography column, specifically Ni-NTA resin, (i.e., purification dialysis) (pg. 51, section 2.7.2 Large scale protein purification, IMAC).
Claim Rejections - 35 USC § 103
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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Yosaatmadja (Ester bond formation in bacterial adhesins; Thesis, University of Auckland Research Repository, August 2018) in view of Kwon et al (Autocatalytically generated Thr-Gln ester bond cross-links stabilize the repetitive Ig-domain shaft of a bacterial cell surface adhesin; PNAS, 2014, 11(4):1367-1372), as evidenced by Novagen (pET-22b(+) Vector, Retrieved from Date: Nov 09, 2021).
Regarding claims 5-6, the teachings of Yosaatmadja’s method for purifying Cpe0147 is discussed above and applied to claim 4. Yosaatmadja teaches a list of vectors used for expression of Cpe0147 with different tags and cleavage methods (Table 2.3). Yosaatmadja also teaches the expression vector has a “multiple cloning site” that allow target gene ligation (pg. 75, first paragraph), and EcoRI and KasI restriction endonucleases are used for digestions (pg. 84, section 3.2.1).
However, Yosaatmadja does not teach wherein the vector is pET-22b and wherein the restriction enzyme sites ligated to the vector are NdeI and XhoI.
Kwon et al teaches a method of expressing and purifying Cpe0147 by cloning its gene sequence into a pET-22b vector and expressing Cpe0147 in E. coli 21(DE3) cells as C-terminal His-tagged proteins for downstream purification by nickel-affinity chromatography, followed by size-exclusion chromatography (pg. 1371, subsection Gene Synthesis, Protein Expression, and Purification).
In addition, Novagen discloses that pET-22b vector has a multiple cloning site comprising multiple restriction enzyme sites between promoter and His-tag sequences, which include NdeI and XhoI at the 5’- and 3’-ends (pg. 1).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have modified Yosaatmadja’s method to use a pET-22b vector and restriction enzyme sites NdeI and XhoI because it would have merely amounted to a simple substitution of a bacterial expression vector with known function to yield predictable results. The expression vectors used by Yosaatmadja and Kwon et al serve the same purpose to express Cpe0147. Similarly, the restriction enzyme sites’ sequences are known and they serve the same purpose to create overhangs on DNA fragments for subsequent ligation into a recombination plasmid. One would have been motivated to have done so for the advantage of expressing and purifying Cpe0147 without the need to cleave expression tag as taught by Kwon et al, and conveniently choosing the NdeI and XhoI sites already designed on the 5’- and 3’- ends of the multiple cloning site on the pET-22b vector. One would have had a reasonable expectation of success in doing so because both Yosaatmadja and Kwon et al teach method to express and purify the same protein.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Yosaatmadja (Ester bond formation in bacterial adhesins; Thesis, University of Auckland Research Repository, August 2018) in view of Young et al (Molecular Superglues: Discovery and Engineering Orthogonalization; Chapter 6, Protein Nanotechnology: Protocols, Instrumentation, and Applications, Methods in Molecular Biology, 2020, 2073:85-99).
Regarding claim 8, Yosaatmadja teaches E. coli BL21 (DE3) is cultures in Terrific Broth medium (pg. 49, section 2.6 Recombinant protein expression).
However, Yosaatmadja does not teach culturing E. coli BL21 (DE3) in LB medium.
Young et al teaches expressing Cpe0147 in E. coli BL21(DE3) cells by culturing in LB medium (pg. 92, steps 12 and 13) and expression is induced with IPTG, followed by centrifugation, sonication, purification and dialysis as required in the method of claim 4 (pg. 92, steps 12-17).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have modified Yosaatmadja’s method to culture BL21(DE3) cells in LB medium as taught by Young et al because it would have merely amounted to a simple substitution of a bacterial culturing media with known function to yield predictable results. The TB medium used by Yosaatmadja and LB medium used by Young et al serve the same purpose to express Cpe0147. One would have had a reasonable expectation of success in doing so because both Yosaatmadja and Young et al teach method to express and purify Cpe0147 using E. coli BL21 (DE3) cells.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Yosaatmadja (Ester bond formation in bacterial adhesins; Thesis, University of Auckland Research Repository, August 2018) in view of Thermo Fisher Scientific (Dialysis Methods for Protein Research; Retrieved for Date: March 08, 2021) and Nakajo et al (Purification and Characterization of a Novel Brain-Specific 14-kDa Protein; Journal of Neurochemistry, 1990, 55(6):2031-2038).
Regarding claim 10, the teachings of Yosaatmadja regarding the method for purifying Cpe0147 protein is discussed above as applied to claim 4. Yosaatmadja teaches dialyzing the purified protein of 13.6 kDa overnight (pg. 52, section Proteolytic cleavage and IMAC, and Figure 3.13C caption).
However, Yosaatmadja does not specify the dialysis bag is 3,000 Da and dialysis is conducted for 24-26 h.
Thermo Fisher Scientific discloses that dialysis membranes are commercially available in a range of molecular weight cut-off (MWCO) that “describes the smallest average molecular mass of a molecule that fails to diffuse across the dialysis membrane. For example, a membrane with a 10K MWCO will retain more than 90% of proteins with a molecular mass of 10 kDa or greater.” (pg. 4, first paragraph). Thermo Fisher Scientific further discloses commercially available dialysis membranes with MWCOs including 2 kDa, 3.5 kDa, and 7kDa (pg. 4, first paragraph).
In addition, Nakajo et al teaches purification of a 14-kDa protein (comparable size to Cpe0147) and dialysis for 24 h (pg. 2032, col. 1, para. 1).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have modified Yosaatmadja’s method to use a dialysis bag having a MWCO lower than the molecular weight of the purified protein because it would have merely amounted to a simple substitution of dialysis membranes with known MWCO to yield predictable results. The dialysis membrane used in Yossatmadja’s method and commercially available dialysis membranes of 2 kDa or 3.5 kDa serve the same purpose to retain the purified protein while allowing smaller molecules to pass through. One would have been motivated to have done so for the advantage of maximizing protein retention by reducing the risk of losing the purified protein through dialysis membranes with a higher MWCO. One would have had a reasonable expectation of success in doing so because Yosaatmadja already teaches the usage of dialysis membranes in the method.
In addition, it would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have modified Yosaatmadja’s method to dialyze the purified protein for 24 h as taught by Nakajo et al because it would have merely amounted to a simple substitution of dialysis duration to yield predictable results. The purified proteins in both Yosaatmadja and Nakajo are comparable size and extending dialysis duration serve the same purpose to exchange buffer and remove undesired contaminants. One would have been motivated to have done so for the advantage of maximizing removal of unwanted salt and small protein contaminants. One would have had a reasonable expectation of success in doing so because Nakajo et al teaches dialysis for 24 h is predictable and Yosaatmadja already teach dialysis overnight and extending dialysis duration is not unpredictable.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 4-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-10 of copending Application No. 18/255,108 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claims 4-10, ‘108 teaches a method for purifying a molecular peptide mutant that is originated from bacteria by introducing a gene sequence of the molecular peptide mutant into a vector to construct a recombinant plasmid, and further introducing the recombinant plasmid into a host bacterium (claim 4, step (1)). Further, claims 4-10 of ‘108 teaches all remaining steps (2) to (4) of instant claim 4, and all limitations in the same combination in instant claims 5-10.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Subject Matter Free of Prior Art
The following subject matter is free of prior art: A Cpe0147 peptide mutant obtained from Clostridium perfringens, wherein the peptide mutant consists of an amino acid sequence set forth in SEQ ID NO: 1, and wherein the peptide mutant forms an ester bond.
State of the art of the record: Kwon et al (Autocatalytically generated Thr-Gln ester bond cross-links stabilize the repetitive Ig-domain shaft of a bacterial cell surface adhesin; PNAS, 2014, 11(4):1367-1372) teaches a putative cell-surface adhesin from Clostridium perfringens (Cpe0147) has an adhesin domain and 11 repeat domains (Fig. 1), and analysis of bond geometry and interatomic contacts revealed suggests ester bond formation between Thr and Gln in a single putative domain construct (C1), which aligns with claimed peptide mutant of SEQ ID NO: 1 without mutations. Kwon et al further teaches key residues for ester bond formation involving threonine, histidine, glutamic acid and glutamine at specific positions. In addition, Squire et al (WO 2018/093274 A1; Published Date: May 24, 2018) teaches a binding partner comprising amino acids 439-563 of Cpe0147 from C. perfringens spontaneously forms one or more ester bonds with a peptide tag comprising amino acids 565-587 also of Cpe0147 from C. perfringens ([0023], [0025], [0026], and [0028]). Squire et al further teaches wherein “one of the amino acids is a reactive residue capable of spontaneously forming an intermolecular ester bond” selected from the group comprising threonine, serine, glutamine, and glutamic acid ([0028]).
In summary, the state of the art discloses key residues necessary to retain structure and function and no prior art teach or suggest mutations included in SEQ ID NO:1 to improve folding stability of Cpe0147 without affecting its structure and function.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to QIWEN SU-TOBON whose telephone number is (571)272-0331. The examiner can normally be reached Monday - Friday, 9:30am - 5:00pm.
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, Neil Hammell can be reached at 571-270-5919. 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.
QIWEN SU-TOBON
Examiner
Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
Prosecution Insights