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 .
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in KR on 11/03/2023. It is noted, however, that applicant has not filed a certified copy of the KR10-2023-0150738 application as required by 37 CFR 1.55. Therefore, the effective filing date of the instantly claimed invention is 11/01/2024.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/01/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawing Objections
The drawings are objected to because Figures 1-18 are blurry, and details and words cannot be ascertained on any images or figures. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 103, Obviousness
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.
Claims 1 and 3-8 are rejected under 35 U.S.C. 103 as being unpatentable over Donovan (US 2018/0195055; Date of Publication: July 12, 2018) in view of Ryeol (KR 2018/0061488; Date of Publication: June 8, 2018).
Donovan's general disclosure relates to "Genes for four endolysins, PlyCP10, PlyCP18, PlyCP33, and PlyCP41, were found within clusters of phage associated genes, likely prophages from strains Cp10, Cp18, Cp33, and Cp41. PlyCP18 and PlyCP33 harbor L-alanine amidase catalytic domains, and PlyCP10 and PlyCP41 have glycosyl hydrolase catalytic domains as predicted by BlastP and PFAM searches. All four genes were synthesized with E. coli codon optimization, expressed in E. coli expression vectors with a 6×His tag for nickel column purification, and the recombinant proteins purified. The four endolysins were capable of lysing the 66 C. perfringens strains tested" (see, e.g., Donovan, abstract).
Regarding claims 1, 5, and 8 pertaining to the enzymatically active domain (EAD) and cell wall-binding domain (CBD), Donovan teaches phage endolysins "PlyCP10 and PlyCP41 have glycosyl hydrolase catalytic domains which specifically attack the peptidoglycan cell wall of Clostridium perfringens bacteria which contributes to severe gut infections (necrotic enteritis) in animals such as poultry, and new-born cattle and swine" (see, e.g., Donovan, [0002]). Therefore, PlyCP10 and PlyCP41 have enzymatically active domains. Moreover, Donovan teaches lysin PlyCP33 "has a SH3 domain by PFAM and BLASTP analysis with predicted cell wall binding function" against C. perfringens (see, e.g., Donovan, [0073]). Therefore, PlyCP33 has a cell-wall binding domain.
Regarding claim 3 pertaining to EAD and CBD being derived from endolysin proteins of bacteriophages, Donovan teaches PlyCP10, PlyCP18, PlyCP33, and PlyCP41, PlyCP18 and PlyCP33 are phage endolysins against C. perfringens (see, e.g., Donovan, [0002]); therefore,PlyCP10, PlyCP18, PlyCP33, and PlyCP41, PlyCP18 and PlyCP33 are C. perfringens phage endolysin proteins.
Regarding claim 7 pertaining to detecting Clostridium sp. strains, Donovan teaches C. perfringens endolysins PlyCP10 and PlyCP41 specifically attack the peptidoglycan cell wall of Clostridium perfringens bacteria (see, e.g., Donovan, [0002]). Therefore, PlyCP10 and PlyCP41 detects C. perfringens. Moreover, Donovan teaches lysin PlyCP33 "has a SH3 domain by PFAM and BLASTP analysis with predicted cell wall binding function" against C. perfringens (see, e.g., Donovan, [0073]). Therefore, PlyCP33 detects C. perfringens.
However, Donovan does not teach: a spore-binding domain (SBD) (claims 1, 5, and 8); or wherein the SBD is derived from endolysin proteins of bacteriophages (claim 3); or wherein the chimeric endolysin protein comprises a fluorescent protein (claim 6).
Ryeol's general disclosure relates to "bacteriophage-derived spore binding domain exhibiting specific binding to Bacillus cereus spores and to a medium for detection using the domain. The spore binding domain (SBD) developed in the present invention can be a useful medium for detecting Bacillus cereus (B. cereus) spores" (see, e.g., Ryeol, English Translation, Abstract).
Regarding claims 1, 5, and 8 pertaining to the SBD, Ryeol teaches endolysin LysPBC2, which has a spore binding domain (see, e.g., Ryeol, English Translation, Example 3).
Regarding claim 3 pertaining to the SBD being derived from endolysin proteins of bacteriophages, Ryeol teaches that LysPBC2 is derived from a Bacillus cereus phage PBC2 (see, e.g., Ryeol, English Translation, Example 1).
Regarding claim 6 pertaining to the fluorescent protein, Ryeol teaches fusing the CBD of LysPBC2 to EGFP in order to confirm attachment of the CBD to B. cereus (see, e.g., Ryeol, English Translation, Example 2). Additionally, Ryeol teaches fusion of the SBD and CBD together and tagging this fusion protein with EGFP in order to determine if the domains being to spores and cell walls, respectively, by using fluorescence.
It would have been first obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce Donovan's endolysin composition comprising EAD and CBD, wherein the composition also comprises SBD, as taught by Ryeol. One would have been motivated to do so because Ryeol teaches detection of the bacteria in spore form using endolysin proteins because the CBD cannot detect the bacteria when it is in spore form (see, e.g., Ryeol, English Translation, pg. 2). Moreover, Donovan teaches a CBD and EAD derived from endolysin proteins of bacteriophages against C. perfringens (see, e.g., Donovan, [0002], [0073]). Additionally, Donovan teaches "Clostridium perfringens is a Gram-positive, spore forming, anaerobic bacterium commonly present in the intestines of humans and animals. C. perfringens is classified into one of five types (A, B, C, D, or E) based on the toxin production. Spores of the pathogen can persist in soil, feces or the environment, and the bacterium causes many severe infections of animals and humans" (see, e.g., Donovan, [0003]). Therefore, based on the teachings of Donovan and Ryeol, it would have been obvious to produce a composition comprising a SBD against C. perfringens in order to detect C. perfringens when it is in spore form.
It would have been secondly obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce Donovan's endolysin composition comprising EAD and CBD, wherein the CBD domain is fluorescently tagged with EGFP, as taught by Ryeol. One would have been motivated to do so because Ryeol teaches that tagging the CBD and SBD with EGFP allows one to fluorescently detect binding of these domains to the bacterial cell wall and their spores (see, e.g., Ryeol, English Translation, Example 4). Moreover, Donovan teaches lysin PlyCP33 "has a SH3 domain by PFAM and BLASTP analysis with predicted cell wall binding function" against C. perfringens (see, e.g., Donovan, [0073]). Therefore, based on the teachings of Donovan and Ryeol, it would have been obvious to tag PlyCP33 with EGFP in order to monitor binding of PlyCP33 to the cell wall of C. perfringens. One would have expected success because Donovan and Ryeol both teach lysin proteins derived from bacteriophages that target bacteria that produce spores and cause food-borne illnesses.
Regarding claim 4 pertaining to the protein having antibacterial activity against Clostridium sp. strains, this has been interpreted as intended use and does not carry patentable weight. The intended use does not impart a structure limitation for the claimed product (i.e., the chimeric endolysin protein) and the combined prior art of Donovan and Ryeol teaches the instantly claimed composition; therefore, the structure is capable of performing the intended use of antibacterial activity against Clostridium sp. strains.
Regarding claim 5 pertaining to the preamble recitation of "for detecting foodborne disease-causing bacteria", this has been interpreted as intended use and does not carry patentable weight. The intended use does not impart a structure limitation for the claimed product (i.e., the chimeric endolysin protein) and the combined prior art of Donovan and Ryeol teaches the instantly claimed composition; therefore, the structure is capable of performing the intended use of detecting foodborne disease-causing bacteria.
Regarding claim 8 pertaining to the preamble recitation of "for inhibiting foodborne disease-causing bacteria", this has been interpreted as intended use and does not carry patentable weight. The intended use does not impart a structure limitation for the claimed product (i.e., the chimeric endolysin protein) and the combined prior art of Donovan and Ryeol teaches the instantly claimed composition; therefore, the structure is capable of performing the intended use of inhibiting foodborne disease-causing bacteria.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Donovan and Ryeol as applied to claims 1 and 3-8 above, and further in view of Chen (Fusion Protein Linkers: Property, Design, and Functionality; 2013).
The teachings of Donovan and Ryeol, herein referred to as modified-Donovan-Ryeol, are discussed above as it pertains to a composition comprising an AED, SBD, and CBD.
Regarding claim 2 pertaining to a composition comprising an AED, SBD, and CBD, modified-Donovan-Ryeol teaches phage endolysins "PlyCP10 and PlyCP41 have glycosyl hydrolase catalytic domains which specifically attack the peptidoglycan cell wall of Clostridium perfringens bacteria which contributes to severe gut infections (necrotic enteritis) in animals such as poultry, and new-born cattle and swine" (see, e.g., Donovan, [0002]). Therefore, PlyCP10 and PlyCP41 have enzymatically active domains. Moreover, modified-Donovan-Ryeol teaches lysin PlyCP33 "has a SH3 domain by PFAM and BLASTP analysis with predicted cell wall binding function" against C. perfringens (see, e.g., Donovan, [0073]). Therefore, PlyCP33 has a cell-wall binding domain. Moreover, modified-Donovan-Ryeol teaches endolysin LysPBC2, which has a spore binding domain (see, e.g., Ryeol, English Translation, Example 3). Therefore, modified-Donovan-Ryeol teaches a composition comprising an AED, SBD, and CBD.
However, modified-Donovan-Ryeol does not teach: wherein the AED, SBD, and CBD are sequentially linked together (claim 2).
Chen's general disclosure relates to a review of fusion proteins covering "knowledge of fusion protein linkers and summarizes examples for their design and application" (see, e.g., Chen, abstract).
Regarding claim 2 pertaining to sequentially linking AED, SBD, and CBD, Chen teaches that flexible linkers and rigid linkers can be used to produce recombinant fusion proteins by joining multiple protein domains (see, e.g., Chen, Sections 3.1-3.2). Moreover, Chen teaches "naturally-occurring multi-domain proteins are composed of two or more functional domains joined by linker peptides. These linker peptides serve to connect the protein moieties, and also provide many other functions, such as maintaining cooperative inter-domain interactions [21] or preserving biological activity [22]" (see, e.g., Chen, Section 2, pg. 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce modified-Donovan-Ryeol's composition comprising AED, SBD, and CBD, wherein the protein domains are joined or linked sequentially by fusion protein linkers, as taught by Chen. One would have been motivated to do so because Chen teaches "naturally-occurring multi-domain proteins are composed of two or more functional domains joined by linker peptides. These linker peptides serve to connect the protein moieties, and also provide many other functions, such as maintaining cooperative inter-domain interactions [21] or preserving biological activity [22]" (see, e.g., Chen, Section 2, pg. 2). Moreover, modified-Donovan-Ryeol teaches bacteriophage endolysins comprising EAD and CBD in order to target C. perfringens (see, e.g., Donovan, [0002], [0073]), as well as endolysin LysPBC2, which has a spore-binding domain (see, e.g., Ryeol, English Translation, Example 1). Therefore, based on the teachings of modified-Donovan-Ryeol and Chen, it would have been obvious to link the EAD, SBD, and CBD protein domains together sequentially to form a recombinant fusion protein in order to connect the moieties, maintain cooperative inter-domain interactions, and preserve biological activity. One would have been motivated to do so because modified-Donovan-Ryeol and Chen both teach proteins with multiple domains or activities.
Conclusion
Claims 1-8 are rejected.
No claims were allowed.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE IANNUZO whose telephone number is (703)756-5559. The examiner can normally be reached Mon - Fri: 8:30-6:00 EST.
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/NATALIE IANNUZO/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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