DETAILED ACTION
The Non-Responsive Amendment notice of 1/12/26 was sent in error.
Applicant's request for reconsideration of the finality of the Notice of Non-Responsive Amendment mailed on 1/12/26 is persuasive and, therefore, the notice of non-compliance is withdrawn. See Interview summary mailed 1/15/26.
A full first action on the merits is set forth below.
Applicant’s election without traverse of Group I, claims 1-3, 6-9, 14, 16, 19, 26, 28, 29, 31, 38 and 39; Species: SEQ ID NO: 1, in the reply filed on 12/23/25 is acknowledged. It is noted that claim 28 will be examined with respect to the protein only. The antibodies and polynucleotides are in a different group and were deleted from all other pending claims by Applicant.
Claim Rejections - 35 USC § 112-second paragraph
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 1-3, 6-9, 14, 16, 19, 26, 28, 29, 31, 38 and 39 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 7, 8 and 28 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.
Claim 28: The Markush grouping of proteins, nucleic acids/vectors/antibodies is improper in claim 28 because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: they are different biochemically, structurally and functionally. They are different products.
Claims 7 and 8: The Markush grouping of SEQ ID Nos: 1-37 in claims 7 and 8 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: these are different proteins with different amino acid sequences and would elicit different immunogenic responses. Additionally, the search for 37 amino acid sequences along with ‘equivalents or variants thereof’ for each of the 37 sequences would each require the search of the extensive sequence database followed by the analysis of the enormous results that accumulate after the search. This would impose a serious burden on the Examiner.
Advances over the past five-ten years in automated sequencing polynucleotide/polypeptide characterization techniques have made such activities routine. The entire genome of several organisms, including humans, has been determined and deposited into nucleotide and polypeptide sequence databases. The advances in nucleic acid and polypeptide sequencing techniques have also led to the exponential growth in the size of nucleic acid and polypeptide sequence databases and an increase in the number and complexity of such databases. For example, the GenBank® database in 1996 contained 1,021,211 nucleotide sequences. In 2000 the database contained 10,106,023 nucleotide sequences, about a seventeen-fold increase in the number of nucleotides and about a tenfold increase in the number of sequences. In February 2006, the GenBank database contained 59,750,386,305 bases in 54,584,635 sequence records or about a ninety-one-fold increase in the number of nucleotides and about a fifty-four-fold increase in the number of sequences. These factors are responsible for exacerbating the search and examination burden faced by the Office with respect to polynucleotide or polypeptide inventions claimed and described in currently filed applications. It now requires significantly more computational time to run individual nucleotide or polypeptide sequence searches for examination purposes than in 1996, and there is significantly more sequence search results and pertinent prior art to consider. In addition, it currently takes more Office resources to correlate the claimed polynucleotide/polypeptide with the polynucleotide/polypeptide as defined in the prior art because it is increasingly common for both patent applicants and prior art references to describe a polynucleotide/polypeptide molecule in different ways.
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.
Claim 1 is vague and indefinite due to the phrase “without inducing an autoimmune sequelae.” This term is broad and it doesn’t specify which autoimmune disease, the severity, the mechanism (antibody-mediated vs T-cell mediated), whether it’s ongoing or resolved. That’s why it’s often followed by clarification:
“Autoimmune sequelae, including autoimmune thyroiditis and inflammatory arthritis…” The metes and bounds of the term cannot be understood. Appropriate clarification and/or correction is required.
Claim 1 is vague and indefinite because it the mere recitation of a name, i.e., Streptococcus S protein, to describe the invention is not sufficient to satisfy the Statute's requirement of adequately describing and setting forth the inventive concept. 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. The metes and bounds of the term are not understood. 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. Appropriate clarification and/or correction is required.
Claims 1, 7, 8, 9, 16, 19, and 39 are vague and indefinite due to the term “an equivalent thereof.” It is unclear how this is defined and what is meant by “equivalent.” Is this a functional equivalent? A structural equivalent? A variant sequence or an immunogenic fragment?
Claims 9, 14, 16, 19, 28, 29 and 31 are vague and indefinite due to the term "optionally” because it is ambiguous and unclear if the optional materials are part of the claim. Patent claims must be definite and clearly define the boundaries of protected subject matter for skilled artisans. See MPEP 2173.05(h).
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 1-3, 6-9, 14, 16, 19, 26, 28, 29, 31, 38 and 39 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 instant claims are drawn, for example, to:
A method of treating or preventing any Streptococcus infection without inducing an autoimmune sequelae in a subject in need thereof, comprising administering to the subject an effective amount of an isolated Streptococcus S protein or an equivalent thereof, thereby treating or preventing the Streptococcus infection in the subject without inducing an autoimmune sequelae (methods comprising administering any equivalent thereof of from elected sequence, SEQ ID NO: 1 are also claimed).
The method of claim 1, wherein the equivalent comprises: at least about 60% identity to the Streptococcus S protein across the full length of the protein;
or at least 70% of the full length of the protein;
or at least one post-transcriptional modification selected from deamidation, oxidation, dioxidation, formylation, carboxylation, carbamylation, or glycosylation; or an immunogenic fragment of the Streptococcus S protein that is optionally located in the conserved region of the consensus sequence of SEQ ID NO: 38.
To fulfill the written description requirements set forth under 35 USC § 112, 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. Applicants have not described the genus of equivalents thereof and variants of said equivalents and variants of SEQ ID NO: 1 with 60-70% identing and proteins with any of at least one post-transcriptional modification selected from deamidation, oxidation, dioxidation, formylation, carboxylation, carbamylation, or glycosylation, and with the function of treating or preventing any Streptococcus infection without also inducing an autoimmune sequalae, such that the specification might reasonably convey to the skilled artisan that Applicants had possession of the claimed invention at the time the application was filed.
The purpose of the "written description" requirement is broader than tomerely explain how to "make and use"; the applicant must convey with reasonableclarity to those skilled in the art that, as of the filing date sought, he or she was inpossession of the invention. The invention is, for purposes of the "writtendescription" 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 fromits enablement provision; and adequate written description requires more than amere statement that it is part of the invention and reference to a potential methodfor isolating it. The nucleic acid [product] itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. The Guidelines for Examination of Patent Applications Under the 35 U.S.C. 112, paragraph 1, "'Written Description" Requirement (66 FR 1099-1111, January 5,2001) state, "[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" (Id. at 1104). 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. The Guidelines further state, "[f]or 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'" (Id. at 1106);accordingly, it follows that an adequate written description of a genus cannot beachieved in the absence of a disclosure of at least one species within the genus. Asevidenced by Greenspan et al (Nature Biotechnology 7: 936-937, 1999), definingepitopes is not as easy as it seems. Greenspan et al recommends defining anepitope by the structural characterization of the molecular interface between theantigen and the antibody is necessary to define an "epitope" (page 937, column 2).According to Greenspan et al, an epitope will include residues that make contactswith a ligand, here the antibody, but are energetically neutral, or even destabilizingto binding. Furthermore, an epitope will not include any residue not contacted by the antibody, even though substitution of such a residue might profoundly affectbinding. There is a limit to how much substitution can be tolerated before the originaltertiary structure is lost. Therefore, absent a detailed and particular description of arepresentative number, or at least a substantial number of the members of thegenus of fragments or variants or any equivalents of the 37 proteins, let alone from SEQ ID NO: 1, the skilled artisan could not immediately recognize that Applicants were in possession of the claimed genus of protein equivalents and variants at the time of filing.
Therefore, because the art is unpredictable, in accordance with the WrittenDescription Guidelines, the recitation of "a sequence at least 60% identical to oneof SEQ ID No: 1 or any S protein with any changes (and any combination of changes), or any equivalents thereof, which would function in the claimed method. The scope of the claim includes numerous structural variants (i.e. fragments), and the genus is highly variant because a significant number of structural differences between genus members is permitted. One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus with the any equivalents/and variants included, and thus, that the applicant was not in possession of the claimed genus. The claimed subject matter is not supported by an adequate written description because a representative number of species has not been described.
There are no drawings or structural formulas disclosed of any of these“equivalents” or mutants. There is no teaching in the specification regarding which 30-40% of the structure can be varied and still produce a polypeptide with the required function, much less variants or equivalents from these mutants/variants. Although the disclosure of SEQ ID NO: 1 combined with the knowledge in the art, may put one in possession of peptides that are at least 60-70% identical to SEQ ID NO: 1, the level of skill and knowledge in the art is such that one of ordinary skill would not be able to identify without further testing which of those peptides would prevent Streptococcus infection of any species and also not induce autoimmune sequelae. Based on the lack of knowledge and predictability in the art, those of ordinary skill in the art would not conclude that the applicant was in possession of the claimed genus of proteins to be used in the claimed methods.
Claim Rejections - 35 USC § 112-Scope of Enablement
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 1-3, 6-9, 14, 16, 19, 26, 28, 29, 31, 38 and 39 are 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 method of treating or protecting against Group A Streptococcus (GAS) infection comprising administering an effective amount of a recombinant S protein (SEQ ID NO: 1; OR at least 95% identical to SEQ ID NO: 1) to a subject in need thereof.
, does not reasonably provide enablement for:
A method of treating or preventing any Streptococcus infection without inducing an autoimmune sequelae in a subject in need thereof, comprising administering to the subject an effective amount of an isolated Streptococcus S protein or an equivalent thereof, thereby treating or preventing the Streptococcus infection in the subject without inducing an autoimmune sequelae (methods comprising administering any equivalent thereof of from elected sequence, SEQ ID NO: 1 are also claimed).
The method of claim 1, wherein the equivalent comprises: at least about 60% identity to the Streptococcus S protein across the full length of the protein;
or at least 70% of the full length of the protein;
or at least one post-transcriptional modification selected from deamidation, oxidation, dioxidation, formylation, carboxylation, carbamylation, or glycosylation; or an immunogenic fragment of the Streptococcus S protein that is optionally located in the conserved region of the consensus sequence of SEQ ID NO: 38.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The specification states that substitutions, additions, or deletions may be made to the defined sequences; however, the specification provides no guidance as to what the nucleotides may be changed without causing a detrimental effect to the protein and its ability to protect or treat Streptococcus infection. While it is known that many amino acid substitutions are possible in any given protein, the position within the protein’s sequence where amino acid substitutions can be made with a reasonable expectation of success are limited. Other positions are critical to the protein’s structure/function relationship, e.g., such as various positions or regions directly involved in binding, catalysis in providing the correct three-dimensional spatial orientation of binding and catalytic sites. These regions can tolerate only very little or no substitutions. Selective point mutation to one key residue could eliminate the function of the polypeptide. It could eliminate its functional properties. If the range of decreased binding ability after single point mutation of a protein antigen varies, one could expect point mutations in the protein antigen to cause varying degrees of loss of protection/function, depending on the relative importance to the binding interaction of the altered residue. Alternatively, the combined effects of multiple changes, as instantly claimed, in an antigenic determinant could again result in loss of function. A protein having multiple antigenic sites, multiple point mutations, or accumulated point mutations at key residues could create a new antigen that is precipitously or progressively unrecognizable by any of the antibodies in the polyclonal pool. As stated above, Applicants have not shown the particular substitution and the result it produces. Applicants have provided no guidance to enable one of ordinary skill in the art how to determine, without undue experimentation, the effects of different amino substitutions and the nature and extent of the changes that can be made. It is expensive and time consuming to make amino acid substitutions at more than one position, in a particular region of the protein, in view of the many fold possibilities for change in structure and the uncertainty as to what utility will be possessed. See Mikayama et al. (Nov.1993. Proc.Natl.Acad.Sci. USA, vol. 90 : 10056-10060) which teaches that the three-dimensional structure of molecules is important for their biological function and even a single amino acid difference may account for markedly different biological activities. Amino acids owe their ‘significance’ to their inclusion in a pattern which is directly involved in recognition by, and binding to, the receptor and the significance of the particular amino acids and sequences for different amino acids cannot be predicted a priori, but must be determined from case to case by painstaking experimental study. The instant claims allow for substitutions with amino acids of vastly different properties and they do not recite the specific changes in the claims.
The specification also does not enable the treatment or prevention of any Streptococcus infection. The isolated GAS S proteins in the instant specification have been shown to treat or protect against GAS infection, but the specification does not enable a method of treating or preventing infection by all of the Streptococcus species covered by “any” or by the Streptococcus species listed in claim 6. There are no working examples or any evidence provided to support this scope.
The crossprotectivity among different Streptococcus species is unpredictable due to the varying mechanisms of resistance and the complex nature of the immune response. While some studies suggest that certain strains may induce cross-protective immunity, others indicate that this is not always the case. The unpredictability of crossprotectivity highlights the need for further research and the importance of considering the specific strain and context when evaluating immune responses. See Moens et al (Infection and Immunity. May 2012 Volume 80(5): 1944-1945).
Genentech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 clearly states: “Patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable. See Brenner v. Manson, 383 U.S. 519, 536, 148 USPQ 689, 696 (1966) (stating, in context of the utility requirement, that "a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.") Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.”
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-3 is/are rejected under 35 U.S.C. 103 as being unpatentable over D’Aurizio et al (WO 2015/169773 A2; November 2015; provided by Applicants) in view of in view of Wierzbicki et al (Cell Reports. December 3, 2019; 29(10):2979–2989; provided by Applicants).
D’Aurizio et al discloses a method of treating or preventing a Streptococcus infection (a method for the therapeutic or prophylactic treatment of a Streptococcus pyogenes infection; page 10, line 15-16) without inducing an autoimmune sequelae (mutations in a polypeptide for reducing or eliminating the risk of autoimmune sequelae; page 5, lines 16-21) in a subject in need thereof, comprising administering to the subject an effective amount (methods involve administering to the animal (subject) a therapeutic or prophylactic (preventative) amount of the immunogenic compositions of the invention; page 10, lines 17-18) of an isolated Streptococcus protein (recombinantly produced GAS antigens can be isolated from engineered host cells; wherein GAS is Group A Streptococcus pyogenes; page 17, line 31) thereof thereby treating or preventing the Streptococcus infection in the subject without inducing an autoimmune sequelae (mutations in a polypeptide for reducing or eliminating the risk of autoimmune sequelae; page 5, lines 16-21). D’Azurio have developed mutants of GAS40 polypeptides that elicit antibodies that are cross-reactive with wild-type GAS40 but which have reduced sequence identity to amino acid sequences present within human proteins. See also page 5, lines 16-21; page 10, lines 1-3, 10, 15-18; page 17, line 31.
However, D’Aurizio et al does not disclose wherein the treatment comprises administration of an effective amount of one or more of: (i) an isolated Streptococcus S protein, though they do appear to be “equivalent” to the S proteins of the instant invention given their source and similar functional ability.
Wierzbicki et aI teach Group A Streptococcal S protein utilizes red blood cells as immune camouflage and is a critical determinant for immune evasion. Wierzbicki et al characterize a biomimetic red blood cell (RBC)-captured protein of unknown function—annotated subsequently as S protein—in GAS pathophysiology. S protein maintains the hydrophobic properties of GAS, and its absence reduces survival in human blood. S protein facilitates GAS coating with lysed RBCs to promote molecular mimicry, which increases virulence in vitro and in vivo. Proteomic profiling reveals that the removal of S protein from GAS alters cellular and extracellular protein landscapes and is accompanied by a decrease in the abundance of several key GAS virulence determinants. In vivo, the absence of S protein results in a striking attenuation of virulence and promotes a robust immune response and immunological memory. Wierzbicki et al teach that S protein was identified in their original work as a secreted protein, although it was detected in a previously published screen for membrane-bound GAS antigens. To address these divergent findings, a recombinant version of the protein was purified (Figure S1B) and used to raise polyclonal rabbit antisera. Immunoblotting analyses indicated that S protein is abundant both as a cell-associated protein and in the extracellular milieu throughout GAS growth. In the supernatant, it undergoes proteolytic cleavage during stationary phase (Figures 1D and 1E) through a yet-to-be-determined mechanism. See abstract; page 2979, column 1, "Introduction" section, first paragraph; page 2979, column 2, "Introduction" section, last two paragraphs; page 2980; column 1. continued paragraph from page 2979; abstract; page e5, "Bacteria" subsection, first paragraph; page e7, "Purification of Recombinant S Protein and Production of Polyclonal Rabbit Antibodies" subsection, first paragraph.” Wierzbicki et al conclude that due to its highly conserved nature among GAS serotypes and involvement in virulence, S protein is an ideal target for anti-virulence therapeutics. Inactivation of S protein function would make GAS vulnerable to the host immunity. Second, they identified immune pathways that are strongly associated with positive outcomes against GAS infection. Wierzbicki discloses characterization of S protein from Group A Streptococcus sp. as a virulence factor and posits targeting S protein for interventions in Streptococcus pyogenes infections (Streptococcus pyogenes (group A Streptococcus [GAS]) is a health burden that infects humans, wherein a red blood cell-specific effector protein called Spy 0802, otherwise known as S protein, was isolated and characterized, and suggested as a target for pharmacological intervention; page 2979, column 1, "Introduction" section, first paragraph; page 2979, column 2, "Introduction" section, last two paragraphs; page 2980; column 1, continued paragraph from page 2979).
It would have been obvious to a person of ordinary skill in the art, at the time of the invention, to have modified the method as disclosed by D’Aurizio et al to incorporate S protein, as disclosed by Wierzbicki, to provide the benefit of providing a target for developing anti-virulence pharmacological interventions utilizing S protein (Wierzbicki reference; page 2980; column 1, continued paragraph from page 2979).
As per claim 2, D’Aurizio et al and Wierzbicki, in combination, disclose the method of claim 1, but D’Aurizio et al does not disclose wherein the S protein is a Group A Streptococcus (GAS) S protein. Wierzbicki discloses wherein the S protein is a Group A Streptococcus (GAS) S protein (we characterize a biomimetic red blood cell (RBC)-captured protein of unknown function (annotated subsequently as S protein) in GAS pathophysiology; abstract). It would have been obvious to a person of ordinary skill in the art, at the time of the invention, to have modified the method as disclosed by D’Aurizio et al to incorporate S protein, as disclosed by Wierzbicki, to provide the benefit of providing a target for developing anti-virulence pharmacological interventions utilizing S protein (Wierzbicki reference; page 2980; column 1, continued paragraph from page 2979).
As per claim 3, D’Aurizio et al and Wierzbicki, in combination, disclose the method of claim 2, and D’Aurizio et al further discloses wherein the GAS is Streptococcus pyogenes (S. pyogenes) (the composition comprises GAS antigens, wherein GAS is Streptococcus pyogenes (S. pyogenes); page 10, line 1-3 and 10).
Claim(s) 6-9, 14, 16, 19, 26, 28, 29, 31, 38 and 39 is/are rejected under 35 U.S.C. 103 as being unpatentable over D’Aurizio et al (WO 2015/169773 A2; November 2015) and Wierzbicki et al (Cell Reports. December 3, 2019; 29(10):2979–2989; provided by Applicants) in view of Telford et al (US 2006/0210580 A1; provided by Applicants).
The teachings of D’Aurizio and Wierzbicki are set forth above.
The teachings of D’Aurizio et al and Wierzbicki are set forth above. However, they do not particularly exemplify that the S protein comprises SEQ ID NO: 1, 38 or any “equivalents”, variants or mutants thereof, nor do they teach different species of Streptococcus (claim 6). NOTE: the optional portions of the instant claims are not required elements of the claim so the prior art is anticipatory even if it does not contain the” optional” portion of the claims.
Telford discloses a protein which is 100% identical to Applicants’ SEQ ID NO: 1 S protein, e.g., see Telford’s SEQ ID NO: 3666. (instant claims 7-9). See sequence alignment in Public Pair, supplemental content tab. Telford et al teaches the use of adjuvants in claims 7 and 9 (instant claim 14) Telford et al also teaches a protein sequence with fragments that are identical to portions of the S protein (the amino acid sequence comprising UniProt accession number A0A8I2FGE3 (LysM peptidoglycan-binding domain-containing protein comprising an identical gene description to S protein within the BlastP database with Gene ID 900975) comprises 100% identity to SEQ ID NO: 4 of the Telford reference; SEQ ID NO: 4) wherein said protein is from Group B Streptococcus and Telford discloses protein sequences from Group B Streptococcus (proteins from group B streptococcus (Streptococcus agalactiae) and group A streptococcus (Streptococcus pyogenes), including amino acid sequences and the corresponding nucleotide sequences; abstract). It would have been obvious to a person of ordinary skill in the art, at the time of the invention, to have modified the method as disclosed by D’Aurizio et al and Wierzbicki to incorporate the protein sequence for S protein, as disclosed by Telford, to provide proteins are useful antigens for vaccines, immunogenic compositions, and/or diagnostics (Telford reference; abstract).
As per claim 6, D’Aurizio and Wierzbicki, in combination, disclose the method of claim 1, but D’Aurizio and Wierzbicki do not disclose wherein the Streptococcus is selected from the group consisting of Streptococcus equi (S. equi), Streptococcus dysgalactiae (S. dysgalactiae), Streptococcus canis (S. canis), Streptococcus phocae (S. phocae), Streptococcus castoreus (S. castoreus), Streptococcus ictaluri (S. ictaluri), Streptococcus didelphis (S. didelphis), Streptococcus bovimastitidis (S. bovimastitidis), Streptococcus penaeicida (S. penaeicida), Streptococcus porcinus (S. porcinus), Streptococcus pseudoporcinus (S. pseudoporcinus), Streptococcus uberis (S. uberis), Streptococcus iniae (S. iniae), or Streptococcus parauberis (S. parauberis). Telford discloses an amino acid sequence that is 71% identical to an amino acid from expressed from Streptococcus equi (S. equi) (the amino acid sequence expressed from the Gene ID NO: 64011217 from the NCBI Blast Database is 71% identical to SEQ ID NO: 3,666 of the Telford reference; SEQ ID NO: 3,666).
It would have been obvious to a person of ordinary skill in the art, at the time of the invention, to have modified the method as disclosed by D’Aurizio to incorporate any of the large group of Streptococcal species listed since they share homologous protein identity to S protein, as disclosed by Telford, to provide the benefit of Telford, to provide proteins are useful antigens for vaccines, immunogenic compositions, and/or diagnostics (Telford reference; abstract). Since Telford et al teaches the identical protein, e.g., SEQ ID NO: 1, and methods of administration, it would inherently be treating or preventing Streptococcus infection as instantly claimed, without inducing autoimmune sequelae.
Correspondence regarding this application should be directed to Group Art Unit 1645. Papers related to this application may be submitted to Group 1600 by facsimile transmission. Papers should be faxed to Group 1600 via the PTO Fax Center located in Remsen. The faxing of such papers must conform with the notice published in the Official Gazette, 1096 OG 30 (November 15,1989). The Group 1645 Fax number is 571-273-8300 which is able to receive transmissions 24 hours/day, 7 days/week.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
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, Daniel E. Kolker, can be reached on (571) 272-3181.
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 2/2/26