DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-7 and Species: S8 peptidase (Applicants recite in this response that the S8 peptidase it is also referred to as CspC), in the reply filed on 5/14/26 is acknowledged.
Claims 8-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Claims 1 and 3-7 read on the elected species.
Claim Rejections - 35 USC § 112-2nd paragraph rejection
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 1-7 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.
Claims 1-7 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of the 16 different polysaccharides or proteins as a possible single valent composition and the 19 different proteins in any possible combination, e.g., 1 protein and a polysaccharide, 3 of the proteins, 6 of the proteins, 4 of the proteins, in all different combinations and any immunogenic fragments thereof of all of these polysaccharides and proteins, is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
The proteins possess different structure and they do not have a common use, as their “use” is to provide a therapeutic immune response and each different composition would produce a different immune response which could not be predicted. It is well known in the prior art that combination/multivalent vaccines are highly unpredictable. Reduced immunogenicity can occur when multiple antigens are delivered as mixtures. In this situation, the immune system can become overloaded, resulting in an impaired response to any vaccine component. The combination several different antigens into a single multivalent injection may result in competition among the different components and adversely affect the immunogenicity of any individual component. See Fattom et al. Vaccine Vol. 17, Number 2, January 1999, pp. 126-133(8) and NIH GUIDE, Volume 22, Number 28, Multicomponent Vaccine Development, August 6, 1993. The instant specification has not provided results with any of the multitude of combination vaccines recited in instant claims 1-7. Given the inherent unpredictability of combination vaccines combined with the very large and divergent group of antigens recited in the claims, the claims do not constitute a proper Markush grouping.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use, i.e., elicit the same immune response. Otherwise, the claim 1 should be amended to include the elected species.
Claims 1-3 and 5 are vague and indefinite because the mere recitation of a name, i.e., Cell wall protein 21, DUF3794 domain containing proteins, etc., and the FlgG, FlgE, FlgK, etc. in claim 2, and CDT in claim 3, generic toxin antigens in claim 5 (bacterial toxins, environmental toxins, viral toxins?) etc. to describe the invention is not sufficient to satisfy the Statute's requirement of adequately describing and setting forth the inventive concept. These terms constitute laboratory designations and do not convey any particular structure. The claim should provide any structural properties, such as the amino acid sequence of the protein, which would allow for one to identify the protein without ambiguity. The mere recitation of a name does not adequately define the claimed protein(s). Additionally, a “S8 peptidase” is found in many different organisms, e.g., marine sedimentary Photobacterium, Pseudomonas, Arabidopsis thaliana, etc., so is not a distinguishing designation. The best-known S8 peptidase, Subtilisin, was first isolated from Bacillus subtilis in the 1940s. It was identified as an extracellular protein-degrading enzyme produced by the bacterium. During the 1960s and 1970s, researchers determined its amino acid sequence and three-dimensional structure, establishing it as a distinct type of serine protease unrelated to enzymes like Trypsin despite having a similar catalytic mechanism. In the 1990s, with the creation of protease classification systems such as the MEROPS database, these enzymes were formally grouped into the S8 peptidase family (also called the subtilase family). Accordingly, it is unclear which specific S8 peptidase is being reference as no amino acid or other identifying structure is recited in the claims and/or specification. Further, while the specification can be used to provide definitive support, the claims are not read in a vacuum. Rather, the claim must be definite and complete in and of itself. Limitations from the specification will not be read into the claims. The claims as they stand are incomplete and fail to provide adequate structural properties to allow for one to identify what is being claimed. Appropriate clarification and/or correction is required.
Claims 1 and 8 are vague and indefinite for the use of the parentheticals around “or immunogenic fragments thereof” because they leave it unclear if these fragments are part of the claim scope or not. Applicants should delete the parentheses around the words. Appropriate clarification and/or correction is required.
Claim 1 is also vague and indefinite because it recites “mod. protein” in the parentheses after FlgD and “glucosamine domain-cont. protein.” The “mod.” and the “cont.” appear to be abbreviations. An abbreviated word needs to be spelled out the first time it appears in a claim. Appropriate clarification and/or correction is required.
Claim 1 is vague and indefinite because Applicants recite in their Election response of 5/14/26 that the elected S8 peptidase is also known as “CspC.” However, CspC and S8 peptidase are not the same. Unlike S8 peptidases, CspC is not an active protease. It is a pseudoprotease that functions as the spore’s germinant receptor. S8 peptidase is a family of enzymes (proteases) that break down proteins by cutting peptide bonds. They belong to the subtilisin family of serine proteases, meaning they use a serine amino acid at their active site to catalyze protein cleavage. It is also noted the instant specification does not recite the term “CspC.” Appropriate clarification and/or correction is required.
Claim 6 is vague and confusing for the S8 peptidase in a “cell-free preparation.” The metes and bounds of this phrase and its relation to the composition are not clear. It is being interpreted as an “isolated S8 peptidase” in a composition, e.g., not in a recombinant host cell. Appropriate clarification and/or correction is required.
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 1, 6 and 7 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter because the claims are drawn to a protein which exists in nature, e.g., the well-known S8 peptidase. The claimed proteins (and polysaccharides) are not markedly different from what naturally exists in nature. Even though isolation structurally changes a protein from its natural state, the resultant difference is no enough to render the protein markedly different because the genetic structure and amino acid has not been altered. See Myriad, 133 S.Ct. at 2166-18. The claim(s) recite(s) a vaccine composition comprising at the S8 peptidase and a pharmaceutically acceptable carrier or excipient. There is no limitation regarding the structure of the claimed proteins and polysaccharides and they encompass naturally occurring products. A “vaccine composition” is an intended use only, a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, there must be a structural difference between the claimed product or it meets the claim. A “pharmaceutically acceptable carrier or excipient” reads on water and therefore would be inherent in the preparation of the compositions. With regard to “recombinant” polypeptides or “recombinantly produced polypeptides,” if the product in [a] product-by-process claim is structurally the same as a product of a product of nature even though the prior [art] product was made by a different process, the rejection applies. The term “recombinant” also does not automatically confer a structural difference between the claimed invention and the naturally occurring product when the structures are identical.
Claim Rejections - 35 USC § 112-Written Description
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 1-7 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.
The rejected claims are drawn to vaccine compositions polysaccharides and/or proteins (i.e. S8 peptidase, Cell wall protein 12, etc.). Immunogenic fragments to any of these structures are also claimed. There is no limitation with regard to the sequence of any of proteins or where they are derived. To fulfill the written description requirements set forth under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, the specification must describe at least a substantial number of the members of the claimed genus, or alternatively describe a representative member of the claimed genus, which shares a particularly defining feature common to at least a substantial number of the members of the claimed genus, which would enable the skilled artisan to immediately recognize and distinguish its members from others, so as to reasonably convey to the skilled artisan that Applicant has possession the claimed invention. To adequately describe the genus of vaccines, Applicant must adequately describe the claimed products that induce a protective immune response, i.e., vaccine. The specification, however, does not disclose distinguishing and identifying features of a representative number of members of the genus of vaccines to which the claims are drawn, such as a correlation between the structure of the immunogen (the sequence of the proteins generally and the sequences of the proteins specifically (S8 peptidase and the other named structures) and its recited function (vaccines, i.e., inducing a protective immune response), so that the skilled artisan could immediately envision, or recognize at least a substantial number of members of the claimed genus of vaccines. The specification, however, does not disclose any structure associated with the other recited proteins or polysaccharides. As set forth supra, the specification fails to provide a baseline sequence for any of the encompassed proteins and is equally silent with regard which amino acid residues in a given protein are essential for the induction of a protective immune response, or which amino acids might be added, replaced or deleted so that the resultant polypeptide retains the immunological characteristics of its parent. Therefore, the specification fails to adequately describe at least a substantial number of members of the genus of polypeptides to which the claims refer; and accordingly, the specification fails to adequately describe at least a substantial number of members of the claimed genus of vaccines. The specification does not provide substantive evidence that the claimed vaccines are capable of inducing a directed or protective immunity. Without this demonstration, the skilled artisan would not be able to reasonably predict the outcome of the administration of the claimed vaccines, i.e. would not be able to accurately predict if given immune response has been induced. The ability to reasonably predict the capacity of a single immunogen to induce a given immune response (e.g. protective immunity) from in vitro antibody reactivity studies is problematic. Ellis (Vaccines, W.B. Saunders Company, Chapter 29, 1988, pages 568-574) exemplifies this problem in the recitation that "the key to the problem (of vaccine development) is the identification of the protein component of a virus or microbial pathogen that itself can elicit the production of protective antibodies"(page 572, second full paragraph). Unfortunately, the art is replete with instances where even well characterized antigens that induce an in vitro neutralizing antibody response fail to elicit in vivo protective immunity. See Boslego et al (Vaccines and Immunotherapy, 1991, Chapter 17), wherein a single gonococcal pillin protein fails to elicit protective immunity even though a high level of serum antibody response is induced (page 212, bottom of column 2). Accordingly, the art indicates that it would require undue experimentation to formulate and use a successful vaccine without the prior demonstration of vaccine efficacy.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, 'does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed' ”. The courts have decided:
The purpose of the “written description” requirement is broader than to merely explain how to “make and use”; the applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the “written description” inquiry, whatever is now claimed.
See Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991). Furthermore, the written description provision of 35 USC § 112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
MPEP 2163.02 further states, “[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was 'ready for patenting' such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention” See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"). Moreover, because the claims encompass a genus of variant species, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Additionally, MPEP 2163 states:
"A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)”
And:
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. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. 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." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.).
As evidenced by the teachings of Skolnick et al., the art is unpredictable. Skolnick et al. (Trends in Biotechnology 18: 34-39, 2000) discloses the skilled artisan is well aware that assigning functional activities for any particular protein or protein family based upon sequence homology is inaccurate, in part because of the multifunctional nature of proteins (see, e.g., the abstract; and page 34, Sequence-based approaches to function prediction). Even in situations where there is some confidence of a similar overall structure between two proteins, only experimental research can confirm the artisan's best guess as to the function of the structurally related protein (see, in particular, the abstract and Box 2). Thus, one skilled in the art would not accept the assertion, which is based only upon an observed similarity in amino acid sequence that a variant of a given polypeptide would necessarily have a given immunological property. The instant specification has failed to teach or disclose vaccine compositions comprising the claimed polypeptides, polysaccharides and any immunogenic fragments thereof that are capable of inducing a directed or protective immune. The specification fails to teach or disclose data that demonstrates that the claimed vaccines can provide protection against infections caused by a given pathogen. There is no disclosure of subjects that have been immunized with the claimed vaccines nor is there a disclosure of challenge studies that have been conducted to establish the claimed vaccine’s ability to function as a vaccine. Consequently, there is no correlation between structure and function as required by the Written Description requirement.
With respect to comprising and the FlgG, FlgE, FlgK, etc. in claim 2, and CDT in claim 3, the specification provides no identifying structural information for these designations, e.g., amino acid sequence, nor does the specification provided examples with results of these recited multivalent vaccines. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was 'ready for patenting' such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. Moreover, because the claims encompass a genus of variant species, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was "ready for patenting" by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed. 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. See MPEP 2163.20. Accordingly, it follows that an adequate written description of a genus cannot be achieved in the absence of a disclosure of at least one species within the genus. Therefore, absent a detailed and particular description of a representative number, or at least a substantial number of the members of the genus of fragments or variants, the skilled artisan could not immediately recognize that Applicants were in possession of the claimed genus vaccine compositions at the time of filing.
Therefore, because the art is unpredictable, in accordance with the, in accordance with the MPEP and the pertinent case law, the description of claimed polypeptides is not deemed representative of the genus of vaccines to which the claims refer.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 4, 6 and 7 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Helmerhorst et al (US 20190040375 A1; 7/2/19).
Helmerhorst teach gluten-degrading enzymes found in Rothia species bacteria that are subtilisins that belonging to the S8 family of serine protease family. See abstract. Compositions comprising S8 peptidase are taught. Paragraph [0357] teaches the compositions may contain pharmaceutically acceptable excipients, such as vehicles, adjuvants, carriers or diluents that are inherently nontoxic and nontherapeutic, are commercially available. Recombinant expression of S8 peptidase and recombinant polypeptides are also taught. See [0399] [20] wherein the subtilisin is a recombinant protein and [0064] In any aspect described herein, the subtilisin is an isolated recombinant protein. For example, the subtilisin nucleic acid coding sequence is expressed in another organism other than Rothia sp. For example, expression in yeast or Escherichia coli, or any mammalian cells such as COS cells. [0178] The major therapies currently being pursued target the immunogenic gluten peptides and the immune system, e.g. using a vaccine-based strategy. The instant claims include “any immunogenic fragments thereof.” Given that Helmerhorst teaches an S8 peptidase, belonging to the S8 family of serine proteases, the similarity between S8 from other bacteria would be expected to overlap and include ‘immunogenic fragments.’ The claims and specification fail to teach an amino acid sequence or other identifying features of a S8 peptidase from C. difficile and given the name and same function of the peptidase in the prior art and the peptidase instantly claimed, the disclosed S8 peptidase of the prior art reference appears to be identical to Applicants' claimed S8 peptidase and/or at least be included in the scope of “immunogenic fragments thereof.” Since the Patent Office does not have the facilities for examining and comparing Applicant's BPIP with the BPIP of the prior art, the burden of proof is upon applicants to show an unobvious distinction between the material structural and functional characteristics of the claimed S8 peptidase and the S8 peptidase of the prior art. See In re Best, 195 USPQ 430, 433 (CCPA 19&&).
Claim(s) 1, 6 and 7 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Zhang et al (US 20210130833 A1; 5/6/21).
Zhang provides an engineered system comprising a S8 peptidase. See paragraph [0014]. Zhang teaches defense systems in prokaryotes such as bacteria. The defense systems may include proteins and nucleic acids that play roles in the defense of virus and other foreign organisms' attack and invasion. The present disclosure also includes nucleic acids encoding the components of the defense systems and vectors comprising such nucleic acids. The functions and applications of the defense systems herein are not limited to defending bacteria from foreign organisms (e.g., virus). Rather the defense systems may be used in various applications, e.g., as research tools and reagents, therapeutic agents, and diagnostic agents. In some cases, a defense system may be engineered to have a desired function. Such engineered defense system may not have a function related to defending bacteria from foreign organisms. Paragraph [0080] teaches that the defense systems provided herein may be of various types. These defense systems may comprise one or more enzymes that can manipulate (e.g., cleave, eliminate, degrade, etc.) the proteins and nucleic acids from the foreign organisms. In some examples, a host cell with the defense system may be resistant to foreign organism attacks. The term “resistance” to, for example, foreign nucleic acid invasion, encompasses a decrease in activity (e.g. phage genomic replication, phage lysogeny, circularization of phage genome) in bacteria expressing a functional defense system in comparison to bacteria of the same species under the same developmental stage (e.g. culture state) which does not express a functional defense system. According to specific embodiments the decrease provided by such resistance to foreign organism invasion is at least 1.5-fold, at least 2-fold, at least 3-fold, at least 5-fold, at least 10-fold, or at least 20-fold as compared to same in the absence of the functional defense system. Paragraph [0081] teaches that, in some embodiments, the defense systems have an anti-phage activity. The term “anti-phage activity” or “resistant to infection by at least one phage” may encompasses an activity providing increased resistance of a host cell to infection by at least one phage in comparison to the host cell of the same species under the same developmental stage (e.g. culture state) which does not express the functional defense system. In some embodiments, a host cell may comprise a microbial cell. In some embodiments, a host comprises a bacterium. Anti-phage activity or resistance of a host cell to infection by at least one phage may be determined by, for example but not limited to, bacterial viability, phage lysogeny, phage genomic replication or phage genomic degradation, or a combination thereof. Paragraph [0082] In some embodiments, the defense systems may provide a host cell with resistance to foreign nucleic acid invasion. In some embodiments, a defense system described herein, provides the host cell with resistance to a foreign nucleic acid invasion, wherein the foreign nucleic acid invasion comprises resistance to at least one phage infection, or resistance to plasmid transformation, or a combination of resistance to at least one phage infection and resistance to plasmid transformation. In some embodiments, it is the combination of defense systems that provides a host cell with resistance to a foreign nucleic acid invasion. One skilled in the art would appreciate that defense against a foreign nucleic acid invasion may encompass, defending against entry of a foreign nucleic acid into the host cell, as well as, defending against the actions of a foreign nucleic acid that has entered the host cell. In some embodiments, defense against a foreign nucleic acid invasion comprises defense from phage infection. In some embodiments, defense against a foreign nucleic acid invasion comprises defense from plasmid transformation. In some embodiments, defense against a foreign nucleic acid invasion comprises defense against entry of a conjugative element. In some embodiments, defense against a foreign nucleic acid invasion comprises defense against any combination of phage infection, plasmid transformation, and entry of a conjugative element. Paragraph [0086] The defense systems may be from or originate from microorganisms such as bacteria or archaea. In some embodiments, the defense may be from or originate from bacteria. Paragraph [0087] The bacteria from which the S8 peptidase is derived may be Clostridium spp. The instant claims and specification fail to teach an amino acid sequence or other identifying features of a S8 peptidase from C. difficile and given the name and same function of the peptidase in the prior art and the peptidase instantly claimed, the disclosed S8 peptidase of the prior art reference appears to be identical to Applicants' claimed S8 peptidase and/or at least be included in the scope of “immunogenic fragments thereof,” particularly because Zhang teaches the source may be from Clostridium spp. Since the Patent Office does not have the facilities for examining and comparing Applicant's BPIP with the BPIP of the prior art, the burden of proof is upon applicants to show an unobvious distinction between the material structural and functional characteristics of the claimed S8 peptidase and the S8 peptidase of the prior art. See In re Best, 195 USPQ 430, 433 (CCPA 19&&). The term “vaccine” is an intended use only. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Status of Claims:
No claims are presently allowed. The instant claims are drawn to vaccine compositions, e.g., a product/protein. The term “vaccine” is an intended use only. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. A patent for a new method/use of a known product may be obtained, but a patent cannot be obtained for a known product, e.g., when the prior art protein is the same as a protein described in the specification for carrying out the claimed method, it can be assumed the protein will inherently perform the claimed process. In re King, 801 F.2d 1324, 231 USPQ 136 (Fed. Cir. 1986). The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978)
Notes, pertinent prior art not presently relied upon:
S8 peptidase is a family of enzymes (proteases) that break down proteins by cutting peptide bonds. They belong to the subtilisin family of serine proteases, meaning they use a serine amino acid at their active site to catalyze protein cleavage.
The best-known S8 peptidase, Subtilisin, was first isolated from Bacillus subtilis in the 1940s. It was identified as an extracellular protein-degrading enzyme produced by the bacterium.
During the 1960s and 1970s, researchers determined its amino acid sequence and three-dimensional structure, establishing it as a distinct type of serine protease unrelated to enzymes like Trypsin despite having a similar catalytic mechanism.
In the 1990s, with the creation of protease classification systems such as the MEROPS database, these enzymes were formally grouped into the S8 peptidase family (also called the subtilase family).
S8 peptidases are among the most extensively studied proteases because they:
2013: The landmark paper by Joseph A. Sorg and colleagues identified CspC as the bile acid germinant receptor and demonstrated that disrupting CspC markedly reduced the ability of C. difficile to establish infection in an animal model. The authors specifically suggested that blocking CspC could be a therapeutic strategy.
2019: Researchers solved the crystal structure of CspC and showed that it integrates multiple germination signals (bile acids, amino acids, and calcium). This provided a structural framework for rational drug design.
2021 review: A comprehensive review highlighted CspC as one of the principal molecular targets for anti-germination therapies because inhibiting germination prevents all downstream events—vegetative growth, toxin production, and sporulation.
2023: A computational drug-discovery study screened natural compounds predicted to bind and inhibit CspC, proposing several candidate inhibitors for future laboratory testing. These results are in silico rather than experimentally validated.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jennifer E. Graser whose telephone number is (571) 272-0858. The examiner can normally be reached on Monday-Friday from 8:00 AM-4 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Thomas Visone, can be reached at (571) 270-0684.
Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-0500.
/JENNIFER E GRASER/ Primary Examiner, Art Unit 1645 7/1/26
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