DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1, 2, 4, 5, 8, 12, 14-20 and 26, Species Election: SpyAD polypeptide having SEQ ID NO: 33, and the antigen C5a peptidase having SEQ ID NO: 30, in the reply filed on 11/19/25 is acknowledged.
Claims 29, 30, 33, 37, 38, 41, 42, 45, 48, 49, 50, 51, 61, 62 and 65 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Claim Rejections - 35 USC § 112-2nd 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, 2, 4, 5, 8, 12, 14-20 and 26 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is vague and indefinite because it the mere recitation of a name, i.e., a GAS polypeptide antigen or non-GAS carrier and purified cell wall polysaccharide or a peptide glycan-bound capsular polysaccharide, 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 and the source of cell wall/capsular polysaccharide, which would allow for one to identify the conjugate without ambiguity. The mere recitation of a name does not adequately define the claimed product. A “GAS polypeptide antigen” or “non-GAS carrier” are vague and indefinite as the structures are unclear. 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 4 and 5 recite the phrase "variant thereof". In this regard, it is not clear to the skilled person in the art what kind of variants are encompassed within the aforementioned phrase and if the aforementioned variant retains the function/activity of GAS polysaccharide. It is well-known that any mutations to amino acid sequences potentially impair its activity/function, the skilled person would be imposed with undue burden to identify and test each and every possible variant which fall under the scope of the claim. 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.
Claim 5 is vague and indefinite due to the relative term "about" which is used together with a range of values making it unclear as to the boundaries of the claim. 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.
Claim 15 is vague and indefinite as it recites any immunogenic composition comprising any C5a peptidase polypeptide antigen, any SLO polypeptide antigen and any SpyAD-GAC conjugates with any nnAA. The mere recitation of a name 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 conjugate without ambiguity. 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 16 and 17 are vague and indefinite due to the "fragment thereof" because a fragment can read on a single amino acid to many more. The metes and bounds of the term are not readily 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.
Claims 15-19 and 26 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 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 different GAS polypeptides and SpyAD polypeptides is various different combinations are not species of one another, but different conjugates with different structures and different immune capabilities. The search for one may not reveal the other.
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 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, 2, 4, 5, 8, 12, 14-20 and 26 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 recite, for example:
1. (Currently Amended) A polypeptide-polysaccharide conjugate comprising:
(a) a Group A Streptococcus (GAS) polypeptide antigen or a non-GAS carrier polypeptide comprising at least one non-natural amino acid (nnAA), wherein the nnAA comprises a click chemistry reactive group; and
(b) a purified cell wall polysaccharide or a peptidoglycan-bound capsular polysaccharide.
4. (Currently Amended) The polypeptide-polysaccharide conjugate of any one of claim 1, wherein the cell wall polysaccharide is a GAS polysaccharide, or a variant thereof.
16. (Currently Amended) The polypeptide-polysaccharide conjugate of any one of claim 15, wherein the GAS polypeptide antigen is a SpyAD polypeptide, or a fragment thereof.
17. (Currently Amended) The polypeptide-polysaccharide conjugate of claim 16, wherein the SpyAD polypeptide comprises an amino acid sequence that is at least 95% identical to set forth in SEQ ID NO: 33, or a fragment thereof, or a sequence at least 95% identical thereto.
Claim 1 does not define the possible combinations and characteristics of polypeptide-polysaccharide conjugates required for the invention as noted in the 112, 2nd paragraph rejection above. The specification does not provide proper written description for the breadth of the claims.
Part a) of claim 1 encompasses an infinite number of possible polypeptides. The expression "GAS polypeptide antigen" encompasses any polypeptide and fragment thereof comprised in GAS which is antigenic, including polypeptides which have not been shown to function as an antigen yet. Moreover, the expression "carrier polypeptide" is not clearly defined. It encompasses every polypeptide which would be suitable as a carrier, including those not described in the art yet, however it is not apparent which features a polypeptide needs to have in order to be suitable as a "carrier". Moreover, from the wording of claim 1 it is not clear whether "at least one non-natural amino acid (nnAA)" is a limiting feature only for the non-GAS carrier polypeptide, or if it applies also to the "GAS polypeptide antigen". Regarding part b) of claim 1, the expression "purified cell wall polysaccharide" does not imply which organism the cell wall polysaccharide has been purified from. For example, bacteria, fungi, algae and higher plants all have cells surrounded by cell walls. Similarly, the nature of the "peptidoglycan- bound capsular polysaccharide" is not clearly defined, many types of gram- positive and gram-negative bacteria are surrounded by capsules. Again, it is not apparent whether the limitation "having a molecular weight of at least about 10 kDa to at least about 40 kDa" applies only to the "capsular polysaccharide", or to the "purified cell wall polysaccharide" as well.
In this regard, the specification as filed describes an immunogenic composition comprising C5a peptidase polypeptide antigen of SEQ ID NO: 30, SLO polypeptide antigen of SEQ ID NO: 50 and any one of SpyAD- GAC conjugates CNJ-AE, CNJ-AF and CNJ-AG which comprise SpyAD of SEQ ID NO: 34 with 4 pAMF, and that the immunogenic composition is capable of eliciting immune response in an in vivo rabbit model (Biological Example 5 of the specification as filed). However, it is not immediately apparent to the skilled person if similar immune response can be elicited by any immunogenic composition comprising any C5a peptidase polypeptide antigen, any SLO polypeptide antigen and any SpyAD-GAC conjugates with any nnAA encompassed within the scope of the claims. Since it is well-known that any mutations to amino acid sequences potentially impair its activity/function, the skilled person would be imposed with undue burden to identify and test each and every possible variant which fall under the scope of the claims.
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. 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'" (Id. at 1106); 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.
It is noted that MPEP 2111.01 states that "[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow. The Court of Appeals for the Federal Circuit has recently held that a "written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." University of California v. Eli Lilly and Co., 1997 U.S. App. LEXIS 18221, at *23, quoting Fires v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993). To fully describe a genus of genetic material, which is a chemical compound, applicants must (1) fully describe at least one species of the claimed genus sufficient to represent said genus whereby a skilled artisan, in view of the prior art, could predict the structure of other species encompassed by the claimed genus and (2) identify the common characteristics of the claimed molecules, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these (paraphrased from Enzo Biochemical).University of Rochester v. G.D. Searle & Co. (69 USPQ2d 1886 (2004)) specifically points to the applicability of both Lilly and Enzo Biochemical to methods of using products, wherein said products lack adequate written description. While in University of Rochester v. G.D. Searle & Co. the methods were held to lack written description because not a single example of the product used in the claimed methods was described, the same analysis applies wherein the product, used in the claimed methods, must have adequate written description (see Enzo paraphrased above).
In the instant case, there is no structure associated with function with regard to the members of A polypeptide-polysaccharide conjugate comprising a Group A Streptococcus (GAS) polypeptide antigen or a non-GAS carrier polypeptide comprising at least one non-natural amino acid (nnAA), wherein the nnAA comprises a click chemistry reactive group and a purified cell wall polysaccharide or a peptidoglycan-bound capsular polysaccharide, and variants and fragments thereof. The specification does not describe the structure for all SpyAD and fragments thereof or for any C5a peptidase polypeptide antigen, any SLO polypeptide antigen and any SpyAD-GAC conjugates with any nnAA that shows recited activity. The genus of conjugates in the claims is an extremely large structurally and functionally variable genus. An argument can be made that the recited genus of polypeptides is adequately described by the disclosure of the structure of recited SEQ ID NOS. and one could use structural homology to isolate those genes encoding polypeptides and the encoding polynucleotides recited in the claims. However, as described below, the art clearly teaches the "Practical Limits of Function Prediction": With the written description of a genus, however, merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus. See Ariad, 598 F.3d at 1353 (The written description requirement guards against claims that "merely recite a description of the problem to be solved while claiming all solutions to it and . . . cover any compound later actually invented and determined to fall within the claim's functional boundaries."). Abbvie Deutschland GmbH & Co. v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 U.S.P.Q.2d 1780, 1790, 2014 BL 183329, 12 (Fed. Cir. 2014).
Devos et al., (Proteins: Structure, Function and Genetics, 2000, Vol. 41: 98-107), teach that the results obtained by analyzing a significant number of true sequence similarities, derived directly from structural alignments, point to the complexity of function prediction. Different aspects of protein function, including (i) enzymatic function classification, (ii) functional annotations in the form of key words, (iii) classes of cellular function, and conservation of binding sites can only be reliably transferred between similar sequences to a modest degree. The reason for this difficulty is a combination of the unavoidable database inaccuracies and plasticity of proteins (Abstract, page 98) and the analysis poses interesting questions about the reliability of current function prediction exercises and the intrinsic limitation of protein function prediction (Column 1, paragraph 3, page 99) and conclude that "Despite widespread use of database searching techniques followed by function inference as standard procedures in Bioinformatics, the results presented here illustrate that transfer of function between similar sequences involves more difficulties than commonly believed. Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, and page 105).Whisstock et al., (Quarterly Reviews of Biophysics 2003, Vol. 36 (3): 307-340,) also highlight the difficulties associated with "Prediction of protein function from protein sequence and structure": "To reason from sequence and structure to function is to step onto much shakier ground", closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function, in such cases, assignment of function on the basis of homology, in the absence of direct experimental evidence, will give the wrong answer (page 309, paragraph 4), it is difficult to state criteria for successful prediction of function, since function is in principle a fuzzy concept. Given three sequences, it is possible to decide which of the three possible pairs is most closely related. Given three structures, methods are also available to measure and compare similarity of the pairs. However, in many cases, given three protein functions, it would be more difficult to choose the pair with most similar function, although it is possible to define metrics for quantitative comparisons of different protein sequences and structures, this is more difficult for proteins of different functions (page 312, paragraph 5), in families of closely related proteins, mutations usually conserve function but modulate specificity i.e., mutations tend to leave the backbone conformation of the pocket unchanged but to affect the shape and charge of its lining, altering specificity (page 313, paragraph 4), although the hope is that highly similar proteins will share similar functions, substitutions of a single, critically placed amino acid in an active-site residue may be sufficient to alter a protein's role fundamentally (page 323, paragraph 1). C. This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polypeptides do not necessarily share the same function and many functionally similar proteins will have little or no structural homology to disclosed proteins. For example, proteins having similar structure have different activities (structure does not always correlate to function); Witkowski et al., (Biochemistry 38:11643-11650, 1999) teaches that one conservative amino acid substitution transforms a beta -ketoacyl synthase into a malonyl decarboxylase and completely eliminates beta-ketoacyl synthase activity. The art also teaches that functionally similar molecules have different structures; Kisselev L., (Structure, 2002, Vol. 10: 8-9) teach that polypeptide release factors in prokaryotes and eukaryotes have same function but different structures.
As it is discussed above, a minor change in structure may result in changes affecting function, since, the specification provided no additional information (species/variant/mutant) correlating structure with function, one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed. Furthermore, "Possession may not be shown by merely describing how to obtain possession of members of the claimed, genus or how to identify their common structural features" (See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895). A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does (function), rather what it is (structure), see University of California v. Eli Lilly & Co., 43 USPQ2d 1938, thus above claims lack adequate written description.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov
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, 2, 4, 5, 8, 12, 14-20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gao et al (Infectious Microbes & Diseases. Published 12/29/2020; 3(2): 87-100; provided by Applicants).
Gao discloses the same subject matter as the present claims. Gao discloses polypeptide-polysaccharide conjugates comprising a GAS polypeptide antigen (such as SpyAD, SLO, or C5a peptidase) with a nnAA (such as pAMF) comprising a click chemistry group, which is conjugated to a cell wall polysaccharide which lacks the GlcNAc side chain (see whole document, including: figures 1. 2; abstract). Gao has produced conjugates with different molecular weights between 135 kDa and 2000 kDa (see figure 2D). Gao has used pAMF substitution at positions K64, K287, K386, and K657 of SpyAD (see page 97, left-hand column, last paragraph). Gao discloses the immunogenic composition of claim 29, for example: "Active immunization of mice with a multivalent vaccine consisting of SpyAD-GACPR in combination with candidate vaccine antigens SLO and C5a peptidase provided significant protection against GAS challenge" (see page 88, right-hand column, last paragraph).
Gao discloses a polypeptide-polysaccharide conjugate SpyAD[4pAMF]- GACPR comprising ("Generation of SpyAD-GACPR conjugate" under Results; "Cloning, Expression and Purification of SLO, C5a peptidase, and SpyAD[4pAMF]" under Methods): (a) a Group A streptococcus (GAS) Streptococcus pyogenes Adhesion and Division (SpyAD) conjugate polypeptide comprising four non-natural amino acid (nnAA) at positions K64, K287, K386 and K657, linked to (b) a mutant GAS cell wall carbohydrate containing only polyrhamnose that lacks an immunodominant N- acetyl Glucosamine (GlcNAc) side chain and the surface hyaluronan capsule. D1 also discloses the conjugation involves dibenzocyclooctyne (DBCO)-derivatization of the GAC at a degree between 5-10% before it was mixed with SpyAD[4pAMF] at a 1:1 ratio to facilitate conjugation via click chemistry ("Dibenzocyclooctyne (DBCO)-derivatization of GAC and conjugation to SpyAD[4pAMF]" under Methods; Figure 2A). Gao further discloses that excess unreacted free polysaccharide was removed post- conjugation ( "Dibenzocyclooctyne (DBCO)-derivatization of GACPR and conjugation to SpyAD[4pAMF]" under Methods). In addition, Gao discloses active immunization of mice using SpyAD-GACPR + Streptolysin O (SLO) + C5a peptidase triple combination vaccine resulted in protection against systemic and localized skin M1 GAS infection ("Immunization with a multivalent glycoconjugate vaccine provides significant protection against systemic and intradermal GAS challenge" in Results; fourth paragraph of Discussion; Figure 6A).
Claim(s) 1, 3, 4, 12, 14 and 26 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Straussman et al (US 2020/0054739; 2/20/20; provided by Applicants).
Straussman et al discloses a polypeptide-polysaccharide conjugate comprising a carrier protein comprising a non-natural amino acid with a click chemistry group conjugated to a polysaccharide (see abstract; claims 1, 2, 4, 25, 27).
Straussman discloses the use of CRM197 as the carrier protein, various click chemistry groups such as azido, and Group A streptococcus cell wall polysaccharides (see paragraphs [0051], [0071], [0094], [0115], [0257], [0299], [0300], [0946]).
Straussman discloses replacing lysine with a nnAA (see paragraph [0206]) and also discloses the use of pAMF as the nnAA (see claim 51 of Straussman).
The reference also discloses the use of CRM197 (see claim 2 of Straussman), including eCRM197 (see paragraph [0073]).
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) 17-20 and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gao et al (Infectious Microbes & Diseases. Published 12/29/2020; 3(2): 87-100; provided by Applicants) in view of Wang et al (CN 107737334; provided by Applicants).
The teachings of Gao are set forth above. Although Gao does not specifically disclose the specific amino acid sequences defined in the claims.
Wang et al discloses amino acid sequence of C5a peptidase of SEQ ID NO: 6 (having 98.62% identity to SEQ ID NO: 2 of the instant application), amino acid sequence of SLO of SEQ ID NO: 15 (which comprises SEQ ID NO: 53 of the instant application) and amino acid sequence of SpyAD of SEQ ID NO: 9 (having 99.87% identity to SEQ ID NO: 33 of the instant application; and having 99.4% identity to SEQ ID NO: 78 of the instant application). Wang discloses a vaccine for preventing A type streptococcal infection. The vaccine provided by the invention has the active ingredients such as ingredient A, ingredient B, ingredient C. ingredient D, ingredient E and ingredient F; the ingredient A is sortase or fusion protein with sortase; the ingredient B is SCPA or fusion protein with SCPA: the ingredient C is Spy0269 or fusion protein with Spy0269; the ingredient D is SCPC or fusion protein with SCPC; the ingredient E is SLO or fusion protein with SLO; and the ingredient F is adjuvant CpG or other mucosal adjuvants. The vaccine provided the invention has the advantages of high efficiency, broad spectrum and low cost. Meanwhile, the vaccine provided by the invention adopts the way of mucosal immunity, has the characteristics of no tissue damage, no local side effect and simple and convenient use, and is easy to popularize and use. Accordingly, it would have been prima facie obvious starting with Gao that any of the sequences recited in Wang could be used, and the C5a antigen C5a peptidase Of Gao would inherently have the amino acid sequence of SEQ ID NO: 30 as evidenced by Wang. Wang also teaches a SpyAD polypeptide having at least 95% identical to SEQ ID NO: 33 or a fragment thereof.
Claim(s) 5 and 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Straussman et al (US 2020/0054739; 2/20/20; provided by Applicants).
The teachings of Straussman et al are set forth above. However, Straussman does not disclose polysaccharides that lack a GlcNAc side chain, conjugates where 10-20 mol% of the polysaccharide repeat units are derivatized by a linker, conjugates with a molecular weight between 185 and 700kDa, the polypeptide antigens of claims 15-23, or a conjugate comprising SpyAD and a GAS polysaccharide.
However, Straussman discloses polysaccharides that are derivatized by a linker (see paragraphs [0297], [0420], [1138]; claims 23, 68. 82). While Straussman does not disclose the specific amount of derivatization used, this appears to be a routine optimization that would be obvious to the person skilled in the art. The present claims define a range of 185-700kDa. Straussman teaches larger conjugates of at least 900kDa (see paragraph [0012]; claim 29), however the skilled person would consider it a matter of routine to test different size conjugates. It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). Since Applicant has not disclosed that the specific limitations recited in instant claims 5 and 8 are for any particular purpose or solve any stated problem and the prior art teaches that the derivatization amounts often vary according to the sample and various matrices, solutions and parameters appear to work equally as well, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges disclosed by the prior art by normal optimization procedures known in the art.
Claim(s) 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Straussman et al (US 2020/0054739; 2/20/20; provided by Applicants) in view of Nizet et al (WO 2013/020090,10/8/2020; provided by Applicants).
The teachings of Straussman et al are set forth above. However, it does not specifically teach that the purified cell wall polysaccharide lacks an immunodominant GlcNAc chain.
Nizet et al discloses GAS glycoconjugates where the polysaccharide lacks the immunodominant GlcNAc side chain (see claim 1 of Nizet; pages 25-26), and indicates that this polysaccharide has reduced autoimmune complications (see page 24, lines 19-24). Accordingly, one of ordinary skill in the art at the time the invention was made would consider it obvious to use the advantageous polysaccharides of Nizet in the glycoconjugates taught in Straussman.
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Straussman et al (US 2020/0054739; 2/20/20; provided by Applicants) and Di Benedetto et al (Inter. J. Molec. Sciences. 2020 21:8558; provided by Applicants).
Di Benedetto discloses glycoconjugate vaccines that comprise a polysaccharide and an antigen such as SpyAD (see abstract of Di Benedetto). One of ordinary skill in the art, faced with the problem of producing GAS vaccines and in light of Straussman and Di Benedetto, would consider it obvious to use the click-chemistry technique of Straussman with the GAC-SpyAD conjugates disclosed in Di Benedetto.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 2, 4, 5, 8, 12, 14-20 and 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 6-8, 10, 17-23, 25, 26, 28-30, 34-39, 41-46, 49-53, 58 and 59 of copending Application No. 17/820,554 (reference application; application just allowed, not Patent No. yet). Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending application claims an immunogenic composition comprising a. a first Group A Streptococcus (GAS) polypeptide antigen that is a C5a peptidase polypeptide antigen comprising the amino acid sequence set forth in SEQ ID NO: 29 or SEQ ID NO: 30 or a fragment thereof; b. a second GAS polypeptide antigen that is SLO; and C. at least one polypeptide-polysaccharide. conjugate comprising a conjugate polypeptide and a conjugate polysaccharide, wherein the conjugate polypeptide is a third GAS polypeptide antigen or a non-GAS carrier polypeptide and comprises at least one non-natural amino acid (nnAA), and wherein the conjugate polysaccharide is a GAS polysaccharide or a variant thereof that lacks an immunodominant N-acetyl Glucosamine (GlcNAc) side chain. The co-pending claims also recite sequences that are identical to Applicant's SEQ ID NOs: 30, 31, 32, 33, and 34, etc. The co-pendingapplication also claims a GAS polysaccharide, or a variant thereof, with a molecular weight of at least about 10 kDa to at least about 40 kDa. Accordingly, the scope of the claims is not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Status of Claims:
No claims are presently allowed.
Pertinent prior art not presently relied upon:
WO 2005/032582; April 2005 discloses a SpyAD polypeptide having a sequence which is 99.4% identical to SEQ ID NO: 78 (SEQ ID NO: 26).
Furthermore, Fairman et al (US 2018/333484) discloses that the molecular weight of capsular polysaccharides from S. pyogenes can be between 10 kDa and 4000 kDa (§181-183).
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 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 3/9/26