DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Amendment
2. The amendment of October 20, 2025 has been entered. Claims 1-36, 38-46 and 48-50 are cancelled. Claims 37, 47, 52, and 56 were amended. Claims 60-62 were newly added. Claims 37, 47 and 51-62 are under consideration in this Office Action.
New Grounds of Rejection Necessitated By Applicants Amendment
Claim Rejections - 35 USC § 112
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.
3. Claim 37 is 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 38 recites the limitation "the size" within the claim. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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)(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.
4. Claims 37, 47, 51, 56-59 and 60-62 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Alexander et al., (US PG Pub 20090317412 published Dec. 2009; priority to June 2004) as evidenced by Ravenscroft et al., (Carbohydr Res 2017 Oct 10;450:19-29. Epub 2017 Aug 18) and evidenced by Shin et al., (WO2021021729).
A vaccine comprising an immunogenic composition comprising an immunologically effective amount of a pneumococcal saccharide-carrier protein conjugate wherein the pneumococcal polysaccharide comprises one or more and less than 500 repeat unit(s) [Wingdings font/0xE0]4) --D-Glcp-(1[Wingdings font/0xE0] 3)-[[-L-Rhap-(1[Wingdings font/0xE0]2)]-[Gro-(2[Wingdings font/0xE0]P[Wingdings font/0xE0]3)]--D-Galp-(1[Wingdings font/0xE0]4)]--L-Rhap-(1 [Wingdings font/0xE0], wherein the size (Mw) of the pneumococcal saccharide is 1-500 kDa and wherein the immunogenic composition comprises 10 or more capsular saccharide from different S. pneumoniae serotypes conjugated to a carrier protein.
Alexander et al., provides conjugates of pan DR binding peptides with Streptococcus pneumoniae polysaccharides, and methods of preventing and treating diseases associated with Streptococcus pneumoniae infection with such conjugates [abstract]. The compositions comprise capsular polysaccharides from at least any five of the following serotypes including: 23A wherein each polysaccharide is conjugated to a separate polypeptide comprising the pan DR binding peptide sequence [para. 0027 and 0078]. It is noted that pneumococcal polysaccharide 23A has the pneumococcal saccharide comprising one or more repeat unit(s) [Wingdings font/0xE0]4) --D-Glcp-(1[Wingdings font/0xE0] 3)-[[-L-Rhap-(1[Wingdings font/0xE0]2)]-[Gro-(2[Wingdings font/0xE0]P[Wingdings font/0xE0]3)]--D-Galp-
(1[Wingdings font/0xE0]4)]--L-Rhap-(1 [Wingdings font/0xE0]. Claims 2, 8 and 13 of Alexander et al., disclose compositions and methods reciting a mixture of at least five Streptococcus pneumoniae capsular polysaccharides from different Streptococcus pneumoniae serotypes, wherein the capsular polysaccharide from each serotype is conjugated to a separate polypeptide comprising a pan DR binding peptide sequence wherein the capsular polysaccharides is 23A further including 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F, 6A, 7A, 7B, 7C, 9A, 9L, 12A, 13, 15A, 15C, 16F, 18A, 18B, 18F, 19B, 19C, 21, 22A, 23A, 23B, 24F, 25, 27, 29, 31, 34, 35, 38, 45, or 46, wherein each polysaccharide is conjugated to a separate polypeptide. The compositions of the invention comprise a mixture of capsular polysaccharides from 10 to 30 or more of these 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F, 6A, 7A, 7B, 7C, 9A, 9L, 12A, 13, 15A, 15C, 16F, 18A, 18B, 18F, 19B, 19C, 21, 22A, 23A, 23B, 24F, 25, 27, 29, 31, 34, 35, 38, 45, or 46 serotypes. [para 78]. The capsular polysaccharide is purified from bacteria of each serotype and conjugated to the polypeptide. In some embodiments, capsular polysaccharide from each serotype is separately conjugated to a polypeptide comprising the pan DR peptide and the resulting conjugates are subsequently combined to form a mixture of conjugates [para. 0028]. In some embodiments the peptides can be synthetically conjugated to other peptides or polypeptides, e.g. chemically conjugated or recombinantly fused [para 35]. Therefore, Alexander et al., disclose a pneumococcal saccharide comprising one or more repeat unit(s) [Wingdings font/0xE0]4) --D-Glcp-(1[Wingdings font/0xE0] 3)-[[-L-Rhap-(1[Wingdings font/0xE0]2)]-[Gro-(2[Wingdings font/0xE0]P[Wingdings font/0xE0]3)]--D-Galp-(1[Wingdings font/0xE0]4)]--L-Rhap-(1 [Wingdings font/0xE0]conjugated to a carrier protein.
A “linker” as used herein is any compound used to provide covalent linkage and spacing between two functional groups (e.g., a pan DR binding peptide and a desired immunogen). Typically, the linker comprises neutral molecules, such as aliphatic carbon chains, amino acids or amino acid mimetics, which are substantially uncharged under physiological conditions and may have linear or branched side chains. In some cases, the linker may, itself, be immunogenic, although non-therapeutically directed. Various linkers useful in the invention are described in more detail, below. Additionally, the verbs “link” and “conjugate” are used interchangeably herein and refer to covalent attachment of two or more species [para 45].
To facilitate the association of the antigenic determinant with the pap DR binding peptide, additional amino acids can be added to the termini of the peptides. The additional residues can also be used for coupling to a carrier, support or larger peptide [para 99]. In some embodiments, polysaccharide/pan DR binding peptide conjugates are linked by a spacer molecule or linker. Alternatively, the polysaccharide may be attached directly to the pan DR binding peptide without a linker [para 103]. Thus teaching instant claim 57. Conjugate pneumococcal vaccine is a seven-valent formulation to a nontoxic diphtheria variant (CRM197) PREVNAR® from Wyeth [para 8]. Multiple antigen peptide (MAP) technology can be used to construct polymers containing both CTL and/or antibody peptides and pan DR binding peptides. When the peptides differ, e.g., a cocktail representing different viral subtypes, different epitopes within a subtype, different HLA restriction specificities, or peptides which contain T helper epitopes, heteropolymers with repeating units may be provided [para 101]. Thus teaching claims 56 and 58. It is desirable to include in the pharmaceutical compositions of the invention at least one component which assists in priming CTL. Lipids have been identified as agents capable of assisting the priming CTL in vivo against viral antigens [para 115]. A combination of streptococcus capsular polysaccharide antigens includes those from Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F [para 79]. Thus teaching claim 59. Alexander et al., describe the polysaccharide being converted into an activated hydrazide. The activated polysaccharide hydrazide may be then conjugated.
The compounds of the present invention, and pharmaceutical and vaccine compositions thereof, can be administered to mammals, particularly humans, for prophylactic and/or therapeutic purposes [para 119]. Vaccine compositions may be administered to a patient susceptible to or otherwise at risk of disease, to elicit and/or enhance an immune response against an antigenic determinant. Such an amount is defined to be an “immunogenically effective dose,” either for therapeutic or prophylactic use [para 121]. Thus teaching instant claim 47. For instance, Streptococcus polysaccharide/pan DR binding peptide mixtures may be used to treat and/or prevent bacterial infection. Streptococcus polysaccharide/pan DR binding peptide conjugates of the invention are used to treat and/or prevent middle ear infections, pneumonia, and meningitis associated with infection of humans or other mammals with Streptococcus pneumoniae [para 119].
Thus, the invention provides compositions for parenteral administration which comprise a solution of the peptides or conjugates dissolved or suspended in an acceptable carrier, preferably an aqueous carrier. A variety of aqueous carriers may be used, e.g., water, buffered water, 0.9% saline, 0.3% glycine, hyaluronic acid and the like [para 132]. Thus teaching the immunogenic composition comprising a pharmaceutically acceptable excipient of instant claim 34. Alexander et al., is directed to vaccines which contain as an active ingredient an immunogenically effective amount of a composition comprising at least one conjugate of the present invention as described herein. The vaccines can also contain a physiologically tolerable (acceptable) diluent such as water, phosphate buffered saline, or saline, and further typically include an adjuvant. Adjuvants such as incomplete Freund's adjuvant, alhydrogel Al(OH)3, aluminum phosphate, aluminum hydroxide, or alum are materials well known in the art [para 120].
The present invention is useful for eliciting an immune response, typically, a humoral response, to antigenic determinants of a carbohydrate immunogen, and in particular Streptococcus pneumoniae capsular polysaccharides [para. 0049]. Thus teaching claim 47. Alexander et al., provides the conjugated capsular polysaccharide serotype 23A from Streptococcus pneumoniae. The patent publication does not disclose the claimed chemical structure. However, the analytical methods concerning the serotypes of Streptococcus pneumoniae are so well established that there cannot be any doubt that the claimed structure is the same as the structure of the polysaccharide disclosed by Alexander et al.
Ravenscroft et al., provide evidence identifying the structure of the serotype 23A capsular polysaccharide is: →4)-β-D-Glcp-(1→3)-[[α-L-Rhap-(1→2)]-[Gro-(2→P→3)]-β-D-Galp-(1→4)]-β-L-Rhap-(1→. The 23A polysaccharide has a disaccharide backbone and disubstituted 2,3-β-Gal as a side chain. Additionally, Ravenscroft et al., teach the 1H NMR spectrum (Fig. 2B) shows signals for the 23A tetrasaccharide. Thus NMR analysis established the structure of the tetrasaccharide repeating unit of serotype 23A polysaccharide as →4)-β-D-Glcp-(1→3)-[[α-L-Rhap-(1→2)]-[Gro-(2→P→3)]-β-D-Galp-(1→4)]-β-L-Rhap-(1→. The repeating unit structure and anomeric configuration of Gal was confirmed by Smith degradation studies which yielded a major oligosaccharide product 23ASD. [2.3. Structure of serotype 23A capsular polysaccharide repeating unit]. Thus, the pneumococcal saccharide comprises less than 500 repeat units, and comprises a tetrasaccharide repeating unit with a disaccharide backbone.
Shin et al., stated the activated serotype 23A capsular polysaccharide may be characterized by different parameters including, for example, the molecular weight (MW) and/or degree of oxidation (Do) [para 81]. An activated Streptococcus pneumoniae serotype 23A polysaccharide before conjugation may have a molecular weight of 300-700 kDa, such as 400-650 kDa, 470-570 kDa, 470-490 kDa, or similar molecular weight ranges. Any whole number within any of the above ranges is an embodiment [para 82]. Inherently the activated 23A of Alexander et al., has a molecular weight of 1-500kDa.
Therefore, Alexander teach the instantly rejected claims.
Response to Arguments
5. Applicant's arguments filed October 20, 2025 have been fully considered but they are not persuasive. Applicants amended the claims to overcome rejection of record. However, the activated 23A pneumococcal saccharide inherently has a molecular weight of 1-500kDa, 10-450kDa, 30-400kDa. “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of an unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that “just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel.” Id.
Therefore, Alexander et al., as evidenced by Ravenscroft et al., and Shin et al., anticipates by the instantly rejected claims because Alexander et al., as evidenced by Ravenscroft et al., and Shin et al., teach every element required by the claim under its broadest reasonable interpretation.
Alexander et al., teach compositions and methods reciting a mixture of at least five Streptococcus pneumoniae capsular polysaccharides from different Streptococcus pneumoniae serotypes, wherein the capsular polysaccharide is conjugated to a carrier protein. The composition comprises 23A and further includes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F, 6A, 7A, 7B, 7C, 9A, 9L, 12A, 13, 15A, 15C, 16F, 18A, 18B, 18F, 19B, 19C, 21, 22A, 23A, 23B, 24F, 25, 27, 29, 31, 34, 35, 38, 45, or 46, wherein each polysaccharide is conjugated to a separate polypeptide. Thus teaching an immunogenic composition comprising an immunologically effective amount of a pneumococcal saccharide-carrier protein conjugate wherein the pneumococcal polysaccharide comprises a tetrasaccharide of repeating units [Wingdings font/0xE0]4) --D-Glcp-(1[Wingdings font/0xE0] 3)-[[-L-Rhap-(1[Wingdings font/0xE0]2)]-[Gro-(2[Wingdings font/0xE0]P[Wingdings font/0xE0]3)]--D-Galp-(1[Wingdings font/0xE0]4)]--L-Rhap-(1 [Wingdings font/0xE0] and 10 or more capsular saccharides from different S. pneumoniae serotypes conjugated to a carrier protein.
Contrary to Applicants assertion, the Office has provided a clear scientific basis Ravenscroft directly states the 23A polysaccharide has a disaccharide backbone and disubstituted 2,3-β-Gal as a side chain and the 23A is tetrasaccharide. Shin et al., clearly teach the 23A polysaccharide having a molecular weight of between 1-500 kDa, therefore Shin et al., provides molecular weight evidence for the 23A.
Alexander et al., teach a vaccine comprising an immunogenic composition comprising an immunologically effective amount of a pneumococcal saccharide-carrier protein conjugate wherein the pneumococcal polysaccharide comprises one or more and less than 500 repeat unit(s) [Wingdings font/0xE0]4) --D-Glcp-(1[Wingdings font/0xE0] 3)-[[-L-Rhap-(1[Wingdings font/0xE0]2)]-[Gro-(2[Wingdings font/0xE0]P[Wingdings font/0xE0]3)]--D-Galp-(1[Wingdings font/0xE0]4)]--L-Rhap-(1 [Wingdings font/0xE0] where Ravenscroft et al., teach a tetrasaccharide repeating unit of serotype 23A and Shin et al., evidences the molecular weight wherein Alexander et al., describes the immunogenic composition comprises 10 or more capsular saccharides from different S. pneumoniae serotypes conjugated to a carrier protein. Therefore, the Office Action establishes a case of anticipation under 35 USC 102.
Claim Rejections - 35 USC § 102
6. Claims 37, 47, 51, 56-57 and 59-62 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Forrest et al., (WO2017173415 published Oct 2017; priority to March 31, 2016 and May 2, 2016) as evidenced by Ravenscroft et al., (Carbohydr Res 2017 Oct 10;450:19-29. Epub 2017 Aug 18).
The claims are drawn to a vaccine comprising an immunogenic composition where the pneumococcal saccharide weighs 1-500 kDa.
Forrest et al., disclose Saccharide-polypeptide conjugates, compositions containing these, methods of making and using the conjugates and compositions [abstract]. Forrest et al., disclose pharmaceutical composition, which can be in unit dose form, comprising a plurality of at least eight unique immunogenic saccharide-polypeptide conjugates each comprising individually a capsular polysaccharide, fragment thereof, or combination thereof conjugated to a polypeptide, wherein the capsular polysaccharide, fragment thereof, or combination thereof is from a unique Streptococcus pneumoniae serotype selected from a group consisting of 2, 6C, 8, 9N, 10A, 11A, 12F, 15A, 15B, 15C, 16F, 17F, 22F, 23A, 23B, 24F, 24B, 31, 33F, 34, 35B, 35F, 38, and Serogroup 20 [para. 0003]. A polypeptide can be conjugated to an immunogenic serotype 23A capsular polysaccharide or fragment thereof isolated from S. pneumonia [para. 0052]. The saccharides or polysaccharides of the invention are depolymerized (sized) to a final range of 100-500 kDa [para 47]. Therefore teaching claims 37 and 60-62. CRM197 can be conjugated to an immunogenic serotype 23A capsular polysaccharide, fragment thereof, or combination thereof isolated from S. pneumonia [para. 0053]. Furthermore, Forrest et al., disclose numerous composition comprising S. pneumonia serotype 23A see [para. 0070]. Therefore, claims 54, 53 and 37 are taught.
FIGURE 7 illustrates the projected expanded coverage provided by a Streptococcus pneumoniae polypeptide conjugate vaccine comprising Streptococcus pneumoniae serotypes 6C, 8, 9N, 10A, 11 A, 12F, 15A, 15B, 15C, 16F, 22F, 23A, 23B, 33F, and 35B against invasive pneumococcal disease (IPD). A pharmaceutical composition administered to a subject can comprise at least ten, fourteen, eighteen, serotypes selected from the group consisting of 2, 6C, 8, 9N, 10A, 11A, 12F, 15A, 15B, 15C, 16F, 17F, 22F, 23A, 23B, 24B, 24F, 31, 33F, 34, 35B, 35F, 38 and Serogroup 20 (comprising serotypes 20A and 20B) [para 82]. Thus teaching instant claim 37 and 47. A pharmaceutical composition administered to a subject can comprise can comprise a plurality of saccharide-polypeptide conjugates comprising the serotype 6C and at least one additional serotype selected from 15A, 15C, 16F, 23A, 23B, and 33B [para 82].
By conjugating a saccharide to a polypeptide, the immune response to the saccharide can be enhanced by inducing a T cell dependent response [para. 0041]. An immunogenic saccharide-polypeptide conjugate can comprise one unique saccharide antigen coupled a polypeptide [para. 0042]. An immunogenic saccharide-polypeptide conjugate composition can be a capsular polysaccharide or fragment of the capsular polysaccharide conjugated to a polypeptide. An immunogenic saccharide-polypeptide conjugate can comprise a saccharide antigen coupled to one or more polypeptides. An immunogenic saccharide-polypeptide conjugate can comprise one unique saccharide antigen coupled a polypeptide. A polypeptide can be any polypeptide that allows for conjugation or coupling of a capsular polysaccharide or fragment of the capsular polysaccharide and can result in the display of the conjugate or coupling in a way that can induce a protective immune response against the capsular polysaccharide or fragment of the capsular polysaccharide. A polypeptide can be CRM197, tetanus toxoid, a diphtheria toxoid, a cholera toxoid, pertussis toxoid, inactivated or mutant pneumococcal pneumolysin, pneumococcal surface protein A, pneumococcal adhesion protein A, pneumococcal lipoprotein PsaA, C5a peptidase group A or group B streptococcus, a non-typable H. influenzae P4 protein, a non-typable H. influenzae P6 protein, M catarrhalis uspA, a keyhole limpet haemocyanin (KLH), OMPC from N. meningitidis, the purified protein derivative of tuberculin (PPD), protein D from H. influenzae, PspA, or any fragment thereof [para 49]. Therefore teaching instant claim 56. CRM197 can be from 58-59 kDa in size. [para 51]. The saccharides or polysaccharides of the invention are depolymerized (sized) to a final range of 100-500 kDa [para 47]. Thus teaching claim 51.
A polysaccharide and polypeptide can be conjugated using 1-cyano-dimethylaminopyridinium tetrafluoroborate (CDAP) chemistry. Thus synthesis can allow for direct coupling to a carrier [para 57]. Thereby teaching instant claim 57. The capsular polysaccharide or immunogenic fragment thereof can be chemically activated and then reacted with the polypeptide. For example, capsular polysaccharides or fragments of the capsular polysaccharides can be reacted with either ammonia or diaminoethane to generate a free terminal amino group. This can then be reacted to a free amino group on the polypeptide to form covalent amide bonds. Thus teaching claim 57.
The vaccine can be used as a prophylactic for disease caused by S. pneumoniae, such as meningitis, pneumonia, and severe invasive diseases associated with pneumococcal infection [para 79]. The saccharide-polypeptide conjugate can be administered by intramuscular injection [para 80]. Example 11 disclose a vaccination of a subject that provides protection against S. pneumoniae for a subject. The aqueous vaccine composition is composed of an immunogenic saccharide-polypeptide conjugate comprising capsular polysaccharides from the S. pneumoniae serotypes 3, 4, 6A, 6C, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15B, 15C, 16F, 19F, 19A, 22F, 23A, 23B, 33F, 35F, 35B, 38 and Serogroup 20 such as serotypes 6C, 8, 9N, 11A, 12F, 15A, 15B, 16F, 22F, 23A, 23B, 33F, and 35B. The aqueous vaccine further contains aluminum phosphate as an adjuvant. After administration, immunity of the subject against S. pneumoniae disease endemic in the United States and Canada is improved. A serotype can refer to the type of a microorganism determined by its constituent antigens. The constituent antigens can be different saccharides, such as different capsular polysaccharides or immunogenic fragments thereof. Some non- limiting examples of S. pneumoniae serotypes can include, but are not limited to 1, 2, 3, 4, 5, 6A, 6B, 6C, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15A, 15B, 15C, 16F, 17F, 18C, 19F, 19A, 22F, 23F, 23 A, 23B, 24F, 24B, 31, 33F, 34, 35F, 35B, 38, and Serogroup 20 (comprising serotypes 20A and 20B) [para 40]. Thus teaching claim 59. The vaccine can be used as a prophylactic for disease caused by S. pneumoniae, such as meningitis, pneumonia, and severe invasive diseases associated with pneumococcal infection [para. 0079]. Thus teaching claim 48. Forrest et al., provides the conjugated capsular polysaccharide serotype 23A from Streptococcus pneumoniae. Forrest et al., do not disclose the claimed chemical structure. However, the analytical methods concerning the serotypes of Streptococcus pneumoniae are so well established that there can be no doubt that the claimed structure is the same as the structure of the polysaccharide disclosed by Forrest et al.
Ravenscroft et al., provide evidence identifying the structure of the serotype 23A capsular polysaccharide is: →4)-β-D-Glcp-(1→3)-[[α-L-Rhap-(1→2)]-[Gro-(2→P→3)]-β-D-Galp-(1→4)]-β-L-Rhap-(1→. Ravenscroft et al., provide evidence identifying the structure of the serotype 23A capsular polysaccharide is: →4)-β-D-Glcp-(1→3)-[[α-L-Rhap-(1→2)]-[Gro-(2→P→3)]-β-D-Galp-(1→4)]-β-L-Rhap-(1→. The 23A polysaccharide has a disaccharide backbone and disubstituted 2,3-β-Gal as a side chain. Additionally, Ravenscroft et al., teach the 1H NMR spectrum (Fig. 2B) shows signals for the 23A tetrasaccharide. Thus NMR analysis established the structure of the tetrasaccharide repeating unit of serotype 23A polysaccharide as →4)-β-D-Glcp-(1→3)-[[α-L-Rhap-(1→2)]-[Gro-(2→P→3)]-β-D-Galp-(1→4)]-β-L-Rhap-(1→. The repeating unit structure and anomeric configuration of Gal was confirmed by Smith degradation studies which yielded a major oligosaccharide product 23ASD. [2.3. Structure of serotype 23A capsular polysaccharide repeating unit]. Thus, the pneumococcal saccharide comprises less than 500 repeat units, where the pneumococcal saccharide comprises a tetrasaccharide repeating unit with a disaccharide backbone. Therefore, Forrest et al., as evidenced by Ravenscroft et al., teach the instantly rejected claims.
Response to Arguments
7. Applicant's arguments filed October 20, 2025 have been fully considered but they are not persuasive. Applicants argue that Forrest et al., does not teach the pneumococcal saccharide has molecular weight of 1-500 kDa,10-450 kDa, 30-400 kDa or 2-200 kDa. However, Forrest et al., describe the saccharides or polysaccharides of the invention are depolymerized (sized) to a final range of 100-500 kDa [para 47]. In this case, Forrest et al., describes a sufficiently specific range that overlaps the instantly claimed ranges. Additionally, the molecular weight of the well known 23A polysaccharide is an inherent feature of the 23A polysaccharide. There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003) (rejecting the contention that inherent anticipation requires recognition by a person of ordinary skill in the art before the critical date and allowing expert testimony with respect to post-critical date clinical trials to show inherency); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) (“[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.”); Abbott Labs v. Geneva Pharms., Inc., 182 F.3d 1315, 1319, 51 USPQ2d 1307, 1310 (Fed. Cir. 1999) (“If a product that is offered for sale inherently possesses each of the limitations of the claims, then the invention is on sale, whether or not the parties to the transaction recognize that the product possesses the claimed characteristics.”); Atlas Powder Co. v. IRECO, Inc., 190 F.3d 1342, 1348-49, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). It is irrelevant that the prior art did not recognize the molecular weight, when the 23A polysaccharide was known in the art.
Therefore, Applicants arguments are not found persuasive and the anticipation rejection of Forrest et al., as evidenced by Ravenscroft et al., is maintained.
Claim Rejections - 35 USC § 102
8. Claims 37, 47, 51 and 52-62 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Faridmoayer (WO 2016020499 published Feb. 11, 2022; priority to Aug 2014) as evidenced by Ravenscroft et al., (Carbohydr Res 2017 Oct 10;450:19-29. Epub 2017 Aug 18) and evidenced by Shin et al., (WO2021021729),
The claims are drawn to a vaccine comprising an immunogenic composition comprising an immunologically effective amount of a pneumococcal saccharide-carrier protein conjugate wherein the pneumococcal polysaccharide comprises cone or more and less than 500 repeat unit(s) [Wingdings font/0xE0]4) --D-Glcp-(1[Wingdings font/0xE0] 3)-[[-L-Rhap-(1[Wingdings font/0xE0]2)]-[Gro-(2[Wingdings font/0xE0]P[Wingdings font/0xE0]3)]--D-Galp-(1[Wingdings font/0xE0]4)]--L-Rhap-(1 [Wingdings font/0xE0] and wherein the immunogenic composition comprises 10 or more capsular saccharide from different S. pneumoniae serotypes conjugated to a carrier protein and method of inducing an immune response.
Faridmoayer teach oligosaccharides or polysaccharides are those oligosaccharides or polysaccharides that comprise a hexose monosaccharides (e.g., glucose) at the reducing end of the first repeat unit, whereas the hybrid oligosaccharides or polysaccharides do not comprise a hexose at the reducing end of the first repeat unit, but instead comprise a hexose monosaccharide derivative. Such hexose monosaccharide derivatives are proper substrates, and thus in the appropriate host cell background can be linked to a carrier protein so as to generate a bioconjugate useful in, e.g., treatment of bacterial disease/infection and/or vaccination against bacterial disease/infection [para. 007]. The bioconjugate of embodiment 120, wherein the Gram positive bacterial capsular saccharide is a Streptococcus pneumoniae serotype 23A, capsular saccharide [para 129]. Shin et al., evidences the serotype 23A capsular polysaccharide may be characterized by its molecular weight (MW) and/or degree of oxidation (Do) [para 81]. An activated Streptococcus pneumoniae serotype 23A polysaccharide before conjugation may have a molecular weight of 300-700 kDa, such as 400-650 kDa, 470-570 kDa, 470-490 kDa, or similar molecular weight ranges [para 82]. Inherently the activated 23A of Faridmoayer has a molecular weight of 1-500kDa and/or 400 kDa.
Embodiment 120: The bioconjugate of embodiment 120, wherein the Gram positive bacterial capsular saccharide is a Streptococcus pneumoniae serotype 8, 14, 15A, 16F, 22F, 23A, 24F, 31 , 33F, 35B or 38 capsular saccharide. [00130] Embodiment 122: The bioconjugate of embodiment 118 wherein the Gram positive bacterial capsular saccharide is a S. aureus serotype 5 or 8 capsular saccharide [para 129].
The bioconjugate of any one of embodiments 120 disclose the carrier protein is detoxified Exotoxin A of P. aeruginosa (EPA), CRM197, maltose binding protein (MBP), Diphtheria toxoid, Tetanus toxoid, detoxified hemolysin A of S. aureus, clumping factor A, clumping factor B, E. coli FimH, E. coli FimHC, E. coli heat labile enterotoxin, detoxified variants of E. coli heat labile enterotoxin, Cholera toxin B subunit (CTB), cholera toxin, detoxified variants of cholera toxin, E. coli Sat protein, the passenger domain of E. coli Sat protein, Streptococcus pneumoniae Pneumolysin and detoxified variants thereof, C. jejuni AcrA, a C. jejuni natural glycoprotein, PcrV (aka LcrV,EspA, SseB), PopB (YopB, YopD, FliC), or OprF, Oprl [para 133]. Teaching claim 56. Thus, is it well known the Streptococcus pneumoniae serotype 23A, capsular pneumococcal saccharide comprises one or more repeat unit(s) —>4)-P-D-Glcp-(1 ->3)-[[-L-Rhap-(1 ->2)]-[Gro-(2->P3)]--D-Galp-(1—>4)]--L-Rhap-(1—> as instantly claimed and evidenced by Ravenscroft et al. Thereby teach claim 52.
The hybrid oligosaccharide or polysaccharide is identical to the donor oligosaccharide or polysaccharide, with the exception of the fact that said hybrid oligosaccharide or polysaccharide comprises a hexose monosaccharide derivative at the reducing end of the first repeat unit in addition to comprising all of the monosaccharides of the donor oligosaccharide or polysaccharide [para 14]. Thus teaching claim 58. The hexose monosaccharide derivative is any monosaccharide which C-2 position is modified with acetamido group such as N-acetylglucosamine (GlcNAc), N-acetylgalactoseamine (GalNAc), 2,4-Diacetamido-2,4,6- trideoxyhexose (DATDH). N-acetylfucoseamine (FucNAc), N-acetylquinovosamine (QuiNAc);, wherein said hexose monosaccharide derivative is N- acetylglucosamine (GlcNAc) [para 16]. Teaching claims 55 and 58.
The hybrid oligosaccharide or polysaccharide having a structure
(B)n— A→ wherein A is an oligosaccharide repeat unit containing at least 2, 3, 4, 5, 6, 7 or 8 monosaccharides, with a hexose monosaccharide derivative at the reducing end (indicated by arrow); wherein B is an oligosaccharide repeat unit containing at least 2, 3, 4, 5, 6, 7 or 8 monosaccharides ; wherein A and B are different oligosaccharide repeat units; and wherein n is at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1, 12, 13, 14, 15, 16, 17, 18, 19, or at least 20 and the B oligosaccharide repeat contains a hexose monosaccharide at the reducing end of the repeat [para 110]. The hexose monosaccharide derivative at the reducing end of the first repeat unit in addition to comprising all of the monosaccharides of the donor oligosaccharide or polysaccharide [para 115]. Thus teaching claim 52-54.
Embodiment 57 disclose the S. pneumoniae capsular polysaccharide is CP23A [para 65]. Embodiment 75 disclose the carrier protein is detoxified Exotoxin A of P. aeruginosa (EPA), CRM197, maltose binding protein (MBP), Diphtheria toxoid, Tetanus toxoid, detoxified hemolysin A of S. aureus, clumping factor A, clumping factor B, E. coli FimH, E. coli FimHC, E. coli heat labile enterotoxin, detoxified variants of E. coli heat labile enterotoxin, Cholera toxin B subunit (CTB), cholera toxin, detoxified variants of cholera toxin [para 83]. ] Various assays can be used to characterize the conjugates described herein, including, molecular weight determination by MS [para 220].
The carrier protein can be introduced into a host cell provided herein for the production of a bioconjugate comprising a carrier protein linked to a hybrid oligosaccharide and polysaccharide [para 225]. Thus teaching claim 57. The vaccine product comprises engineering capsular polysaccharides repeating unit of S. pneumoniae serotypes CP23A [para 213] thus teaching claim 59.
Thus, Faridmoayer disclose a hybrid oligosaccharide or polysaccharide having a structure (B)n— A→ wherein A is an oligosaccharide repeat unit containing at least 2, 3, 4, 5, 6, 7 or 8 monosaccharides, with a hexose monosaccharide derivative at the reducing end (indicated by arrow); wherein B is an oligosaccharide repeat unit containing at least 2, 3, 4, 5, 6, 7 or 8 monosaccharides; wherein A and B are different oligosaccharide repeat units; and wherein n is at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1, 12, 13, 14, 15, 16, 17, 18, 19, or at least 20; thereby teaching claims 55 and 57. The hybrid can be used to treat or prevent a bacterial infection in a subject, comprising administering to the subject the composition and a method of inducing an immune response against a bacterial strain in a subject, comprising administering to the subject the composition [para 107-108].
Therefore, Faridmoayer et al., as evidenced by Ravenscroft et al., disclose the claimed invention.
Response to Arguments
9. Applicant's arguments filed October 20, 2025 have been fully considered but they are not persuasive. Applicants amended the claims to overcome rejection of record. However, the 23A pneumococcal saccharide inherently has a molecular weight of 1-500kDa, and/or 400kDa. MPEP 2112 states “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of an unknown property which is inherently present in the prior art does not make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court stated that “just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel.”
Therefore, Faridmoayer et al., as evidenced by Ravenscroft et al., and Shin et al., anticipates by the instantly rejected claims because Faridmoayer et al., as evidenced by Ravenscroft et al., and Shin et al., teach every element required by the claim under its broadest reasonable interpretation.
Faridmoayer et al., describe a vaccine comprising an immunogenic composition comprising an immunologically effective amount of a pneumococcal saccharide-carrier protein conjugate wherein the pneumococcal polysaccharide comprises one or more and less than 500 repeat unit(s) [Wingdings font/0xE0]4) --D-Glcp-(1[Wingdings font/0xE0] 3)-[[-L-Rhap-(1[Wingdings font/0xE0]2)]-[Gro-(2[Wingdings font/0xE0]P[Wingdings font/0xE0]3)]--D-Galp-(1[Wingdings font/0xE0]4)]--L-Rhap-(1 [Wingdings font/0xE0] where Ravenscroft et al., teach a tetrasaccharide repeating unit of serotype 23A and Shin et al., evidences the molecular weight. Therefore, the Office Action establishes a case of anticipation under 35 USC 102.
Pertinent Art
10. The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure. See also WO2015121783, W2018156491 and 20150202309.
Conclusion
11. No claims allowed.
12. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JA-NA A HINES whose telephone number is (571)272-0859. The examiner can normally be reached Monday thru Thursday.
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/JANA A HINES/ Primary Examiner, Art Unit 1645