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 .
Election/Restrictions
Applicant's election with traverse of Group IV, represented by claims 13, 15, 18, and 19, drawn to a method for producing a payload protein comprising transfecting bacterium with nucleic acid encoding polypeptide of claim 5; and the species SEQ ID NO: 11, X1, enzyme, Bacillus, inflammation, corn, method of reduction in fungal infestation, and amylase in the reply filed on 25 March 2026 is acknowledged.
The traversal is on the ground(s) that all claims of Groups I-IV require the same preprotein signal peptide (XI), defined as an amino acid sequence having at least 90% identity to SEQ ID NOs: 1, 3, 11, or 13.. Applicant’s arguments are found persuasive and therefore the restriction if withdrawn. Furthermore, an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 1, 3, 11, or 13 was found free of the art.
Claims 3-5, 7-8, 12, 19, 27, and 29 are amended. Claims 1-2, 6, 11, 14, 16-17, 28, 31-38, and 40-41 are cancelled. Claims 3-5, 7-10, 12, 13, 15, 18-27, 29, 30, 39 and 42 are pending and being examined on the merits.
Information Disclosure Statement
The information disclosure statement filed 09-08-2023 and 03-01-2024 have been considered.
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.
Claim 5, 7-10, 12, 13, 15, 18-27, 29, 30, 39 and 42 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a polypeptide comprising a formula of X1-Z1 wherein: X1 is a pre-protein signal peptide, and Z1 is a payload protein of endoglucanase; wherein X1 comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 1, 3, 11, or 13 and using a Bacillus bacterial to produce endoglucanase, does not reasonably provide enablement for the secretion of any payload protein using any bacteria as claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Nature of the Invention
The claims are directed to a polypeptide comprising a X1 pre-protein signal peptide having at least 90% identity to the amino acid sequence of SEQ ID NOs: 1, 3, 11, and 13, and a Z1 payload protein. The claims are also directed to engineered bacterium expressing these polypeptides, methods of producing the payload proteins; and methods of treating any or numerous diseases, promoting plant growth, preventing, controlling, or reducing agriculture infestations, and industrial uses using these engineered bacterium.
State of the Art
The art recognized that amino acid substitutions are not uniformly tolerated throughout a protein sequence, protein secretion from signal peptides are not always consistent, and Bacillus subtilis is frequently inefficient. Bowie et al., Science 247:1306-1310 (1990), reported that some amino acid positions accommodate numerous substitutions whereas other positions tolerate few substitutions and that patterns of conservation and variation are related to the local environment of each residue [see pg. 247]. Accordingly, one of ordinary skill in the art would not be able to predict, without substantial experimentation, which of the numerous variants encompassed by the claim possess the characteristics attributed to the disclosed protein, i.e., capable of secreting a protein. Peng (Peng et al. Frontiers in Bioengineering and Biotechnology 9 (2022): 819789) teach that different signal peptides show considerable differences in their ability to drive the secretion of the target protein; the optimum signal peptide for each recombinant protein is not consistent; the optimum signal peptide for one protein secretion could be inefficient for other proteins and vice versa; and that systematic screening of a high-capacity signal peptide library has proven to be a powerful method to identify the optimal signal peptide for a target protein [see Introduction, para 1]. Bolhuis ( teach that despite a high capacity for secretion of homologous proteins, the secretion of heterologous proteins by Bacillus subtilis is frequently inefficient [abstract; see Discussion].
Breadth of the claims
The claims encompass multiple variants of SEQ ID NOs: 1, 3, 11, and 13; the claim encompass may payload proteins, and the claims encompass many uses for these payload proteins.
Guidance of the Specification
The specification teaches that the various signal peptides disclosed herein may be utilized in bacteria to deliver any payload protein to any environment [0139]. The specification only teaches the use of SEQ ID NOs: 1, 11, and 13 although providing a disclosure of different variants of each [Fig. 1; 0058-0080]. The specification provides examples demonstrating secretion of only a limited number of proteins using the disclosed signal peptides [see examples] and does not provide sufficient guidance demonstrating that the disclosed signal peptides or all variants within the 90% will successfully direct secretion of the full breadth of the claimed payload proteins across the full scope of the claims. The specification only teaches the secretion of endoglucanase, a cellulolytic enzyme [0185-0188]. The specification does not provide guidance sufficient to predict which signal peptide variants will successfully secrete which class of proteins, which host strains are suitable for each protein class, and what modifications may be necessary to achieve secretion across the full breadth of the claims. The specification also does not provide guidance to enable one to practice treatment of the full scope of the recited diseases and conditions (or agricultural treatments) using the claimed engineered bacteria given the numerous unrelated diseases and conditions claimed which involves distinct mechanisms of actions and requiring fundamentally different therapeutic strategies.
Experimentation Required
Accordingly, a person of ordinary skill in the art seeking to practice the full scope of the claimed invention would be required to generate numerous sequence variants of the claimed sequences and experimentally evaluate each variant for payload secretion of all protein classes, treatment of all diseases or agricultural treatments. On of ordinary skill would be required to engage in substantial screening and optimization to determine which combination of signal peptide sequence, payload protein, bacterial host, expression conditions, purification conditions, route of administration, and application conditions are operable to practice the full scope of the claims. The need for extensive screening and characterization of numerous variants constitutes undue experimentation under the factors set forth in In re Wands, 858 F.2d 731 (Fed. Cir. 1988).
Taking into consideration the factors outlined above, including the nature of the invention, the breadth of the claims, the state of the art, the guidance provided by the applicant and the specific examples, it is the conclusion that an undue experimentation would be required to make and use the invention as claimed.
Conclusion
Claims 3-4 are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY N GROOMS whose telephone number is (571)272-3771. The examiner can normally be reached M-F 830-530.
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/TIFFANY NICOLE GROOMS/Examiner, Art Unit 1637
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