DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The substitute specification filed 7-10-2025 has bee entered into the record.
Status of Claims
Claims 1, 11-15, 17, 29, 35 and 45-53 are pending.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restrictions
Applicant’s election of Group II and species of SEQ IDNO:51 with S. sureus type 5 capsular saccharide in the reply filed on 3-17-2025 without traverse is acknowledged. Claims 11-15 and 45-51 are under examination. Claims 52 and 53 are withdrawn from consideration as methods of making and methods of use of the elected invention. These methods lack unity of invention with the glycoconjugates in view of the art applied below as the technical feature linking the claims is not “special” within the meaning of PCT Rule 13.2. It is noted that these claims are subject to rejoinder when the all the glycoconjugate claims are allowable.
Claims 1, 17, 29, 35, 52 and 53 are withdrawn from consideration. Claims 11-15 and 45-51 are under examination. SEQ ID NO:42 is free of the art, and the search has been extended to include additional embodiments of claim 11.
Information Disclosure Statement
The information disclosure statements have been considered. Initialed copies are enclosed.
Specification
The disclosure is objected to because of the following informalities:
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Applicant’s attention is specifically drawn to page 8, line 11 and page 63, line 20. Applicant should review the lengthy specification for other embedded hyperlinks for removal.
The disclosure is objected to as reciting a specific four amino acid monomer on page 15, line 33. It is suggest that this sequence be presented as ..”with PSGS (residues #-# of SEQ ID NO:16)”.
The disclosure is also objected to a presenting an amino acid sequence of “LPDTG” at page 20, line 8, which is not followed by a specific sequence identifier. Similarly, it is suggested that applicant identify this sequence as “(residues #-# of SEQ ID NO:X)”.
Claim Objections
Claim 11 objected to because of the following informalities: the claim defines “Y” as any amino acid other than proline, however “Y” is conventionally defined as tyrosine in the literature and in patented claims. Claim 45 objected to because of the following informalities: the claim recites different nomenclature a compared to claim 11 from which it depends. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 11-15 and 45-51 are rejected under 35 U.S.C. 112(a), 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to glyconjugates or bioconjugates, where the protein has one or more glycosites engineered into protein. The claims provide for unlimited placement of a glycosites in a protein and the conjugation of the modified protein by bioconjugation in a host cell or in vitro conjugation either directly or indirectly and are intended for use as an immunogenic composition or a vaccine composition. The proteins and the polysaccharide antigens are without limitation. The elected invention is the Hla of S. aureus, serotype 8 capsular polysaccharide from S. aureus and the consensus sequence of SEQ ID NO:42.
The purpose of the written description requirement is ‘to ensure that the inventor had possession, as of the filing date of the application relied on, of the specific subject matter later claimed by him.’ In re Edwards, 568 F.2d 1349, 1351-52, 196 USPQ 465, 467 (CCPA 1978). The analysis of whether the as-filed specification complies with the written description requirements calls for the Office to compare the scope of the claims with the scope of the description to determine whether Applicants have demonstrated possession of the full scope of the claimed invention at the time of the invention.
In the instant case, the independent claim 11 is representative of the claimed invention. Claim 11 is drawn to a modified polypeptide comprising one or more glycosites having the structure
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and the elected invention contains a sequence that is an Hla sequence that is 95% identical compared to the native Hla of S. aureus (SEQ ID NO:13). The claims encompass an Hla amino acid sequence of SEQ ID NO:13 or 15 or amino acid sequence at least 80%, 85%, 90%, 92%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 13 or 15 (i.e., variants) modified in that the amino acid sequence comprises one or more of the recited consensus sequence where the consensus sequence is inserted at position 131, wherein X and Y are independently any amino acid apart from proline, Z is any amino acid wherein the consensus sequence has been added at C and/or N-terminals, substituted at position 131 (SEQ ID NOS:50-52). The consensus sequence, for example, has independently any amino acid apart from proline and therefore encompasses variants of diverse structure and additionally add zero to nine amino acids at either N-terminal or C-terminal to the glycosylation site as set forth above. The Hla amino acid sequence of the polypeptide variants have specifically enumerated variation at specific positions. The consensus sequence was inserted at specific positions. Clearly, the claimed modified polypeptide and the consensus sequence each represents a huge genus encompassing a large number of modified polypeptide species up to 20% non-identical to SEQ Hla variants comprising structurally variable consensus sequence species. The vast genus of the claimed modified polypeptide is required to have vaccine functions per claim 51. The vast genus of the claimed modified polypeptide is required to treat or prevent Staphylococcus aureus infection in a subject in need thereof as is evident from claim 51. However, at the time of the invention, Applicants were not in possession of the variable genus, the members of which are correlated with the requisite therapeutic and prophylactic vaccine functions in vivo against Staphylococcus aureus infections, and the full scope of the claims.
A sufficient description to show possession of a genus may be achieved by means of disclosure of a representative number of species defined by structure, falling within the scope of the genus, or recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69. The written description requirement can be met by describing the claimed subject matter to a person skilled in the art using sufficiently detailed, relevant identifying characteristics such as functional characteristics, and correlating those functional characteristics with a disclosed structure. See Enzo Biochem v. Gen-Probe, 323 F.3d 956, 964, 967, 968 (Fed. Cir. 2002). A ‘representative number of species’ means that the species which are adequately described are representative of the entire variant genus. When there is substantial variation within the genus as in the instant case, one must describe a sufficient variety of species to reflect the variation within the genus. ‘When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus’. Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005) (Emphasis added). Accordingly, adequate written description of a genus cannot be achieved in the absence of disclosure of a representative number of up to 20% non-identical polypeptide variant species within the structurally variable broad genus, each having the requisite therapeutic and prophylactic vaccine functions in vivo against Staphylococcus aureus infections in a subject. In the instant case, the structure of a representative number of such structurally divergent species within the recited broad genus has not been correlated with the requisite therapeutic and prophylactic vaccine functions in vivo against Staphylococcus aureus infections. A review of the instant specification indicates that at the time of the invention, Applicants were in possession of the isolated modified S. aureus ClfA polypeptide of SEQ ID NO: 15 having the with mutant glycosite of SEQ ID NO: 42 and/or a glycosite at either the N-terminal or C-terminal. However, this species is not representative of the huge genus of up to 20% non-identical polypeptide variants as claimed. There is no evidence that the structure of the glycosite, let alone up to 20% non-identical polypeptide variants of Hla, is correlated with the vaccine function and the therapeutic and prophylactic vaccine functions in vivo against Staphylococcus aureus infections. Additionally, the specification does not demonstrate that a representative number of glycosite variants provide for the function of the ability to quantify bioconjugate glycosylation as contemplated by the specification as filed.
The written description inquiry is case- and context-specific. It “depend[s] on the nature of the claimed invention and the knowledge of one skilled in the art at the time an invention is made and a patent application is filed.” Ariad, 560 at 1372. A number of factors guide the inquiry, including “the existing knowledge in the particular field, the extent and content of the prior art, the maturity of the science or technology, and the predictability of the aspect at issue.” Ariad, 560 at 1372 [Emphasis added]. According to MPEP 2163 [Emphasis added]:
The description needed to satisfy the requirements of (pre-AIA ) 35 U.S.C § 112 “varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence.” Capon v. Eshhar, 418 F.3d at 1357, 76 USPQ2d at 1084. Patents and printed publications in the art should be relied upon to determine whether an art is mature and what the level of knowledge and skill is in the art.
Evidence required to demonstrate possession of the invention is fact-specific and varies inversely with the maturity and predictability of the technology area. Inventions in “unpredictable” arts are subject to greater scrutiny under the written description requirement, and require a greater showing of possession than more predictable arts. In the instant application, this is important because of the unpredictability associated with the ability of up to 20% non-identical polypeptide variants of SEQ ID NO:13 or 15 comprising variable consensus sequence(s) to possess vaccine and therapeutic and prophylactic functions in vivo against Staphylococcus aureus infections or of glycosite quantitative functions. Note that for inventions in emerging and/or unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession. Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089, 118 S. Ct. 1548 (1980) holds that an adequate written description requires ‘not a mere wish or plan for obtaining the claimed ……. invention.’ The facts of AbbVie parallel the claimed invention and provide significant guidance on the inherent unpredictability of protein engineering and the effect of amino acid substitutions on protein function. Abbvie is similar to the Federal Circuit's discussion in Novozymes A/S et al. v. Dupont Nutrition Biosciences APS et al., 2013 WL 3779376, Case No. 2012-1433, C.A. Fed; in both, the Federal Circuit emphasized the unpredictability in the art associated with changes in a parent enzyme or protein that can be effected at one or more positions in the sequence by amino acid addition, deletion, or substitution with at least nineteen other possibilities, e.g. counting natural amino acid residues. The basis of unpredictability is rooted in the same principles that make improvements rare, namely that numerous subtle differences between amino acid residues determine protein binding and function. Because the subtle energetic contributions of each of these interactions is extraordinarily difficult to precisely quantify, and because the number of these interactions is so high even for a single protein-protein interface, innumerable small inaccuracies are amplified into unpredictability. This unpredictability is axiomatic in the field of protein engineering. For example, functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Ariad, 598 F.3d at 1351 ("[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology."); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein). It is true that functionally defined claims can meet the written description requirement if a reasonable structure-function correlation is established whether by the inventor as described in the specification or known in the art at the time of the filing date. Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964 (Fed. Cir. 2002). However, the record here does not indicate such an established structure-function correlation.
In the instant case, encompassed within the scope of the huge genus are numerous structural variants, mutants, homologs, isoforms, fragments, and truncated polypeptide species. The specification does not describe sufficient members representative of the claimed genus by complete structure along with a correlation to the requisite functions. At the time of the invention, despite the high level of skill in the art of biotechnology or biochemistry, one could not have predicted the anti-S. aureus vaccine or therapeutic and prophylactic functions even if one produced up to 20% non-identical polypeptide variant species comprising permitted amino acid additions, deletions, insertions and/or substitutions and comprising the consensus variants. There was no predictability that the resultant variants would retain vaccine functions in vivo and possess anti-S. aureus therapeutic and prophylactic vaccine functions in vivo in a subject. The capacity of such polypeptide variant species to possess or retain the function(s) of the native unmodified polypeptide species was neither predictable, nor has it been established within the instant application at the time of the invention. This is important because the art reflects unpredictability as to which amino acids in a specific protein or a polypeptide sequence can be varied without adversely affecting the functional properties of that specific protein or polypeptide sequence. While it is known in the art that variation in one or more amino acids is possible in a given protein or sequence, the exact position within its amino acid sequence where replacements or variations can be made, with a reasonable expectation of success of retaining the protein’s or polypeptide sequence’s functional competence, is not certain or predictable. A random replacement affecting specific amino acid positions that are critical, for example, to the three-dimensional conformational structure and to a specific property of the protein or polypeptide, would result in a protein or polypeptide that may be non-functional, or not optimally functional, because such positions tolerate no or little modifications. Note that predictability of the aspect at issue is one of the multiple factors to consider under written description analysis. Capon v. Eshhar (CAFC 2005).
With regard to proteins in general, Skolnick et al. (Trends in Biotechnology 18: 34-39, 2000) taught that a skilled artisan is well aware that assigning functional activities for any particular protein or a family of proteins based upon sequence homology is inaccurate, partly because of the multifunctional nature of proteins. See abstract; and page 34. Even in situations where there is some confidence of a similar overall structure between two proteins, only experimental research can confirm the artisan’s best guess as to the function of the structurally related protein. See abstract and Box 2. With regard to the structure-function relationship of an encoded amino acid sequence in general, Rudinger J. (In: Peptide Hormones. (Ed) JA Parsons, University Park Press, pages 1-7, 1976) taught that ‘the significance of particular amino acid sequences for different aspects of biological activity cannot be predicted a priori but must be determined from case to case by painstaking experimental study’. See page 6 of Rudinger. Rudinger further taught that ‘it is impossible to attach a unique significance to any residue in a sequence’ and that a ‘given amino acid will not by any means have the same significance in different peptide sequences, or even in different positions of the same sequence. See page 3 of Rudinger. Even with conservative amino acid substitutions within a protein, the art documents functional unpredictability. For example, Lazar et al. (Mol. Cellular Biol. 8: 1247-1252, 1988) demonstrated that a substitution of the Leu residue with a conservative amino acid residue such as, Ile or His, in the transforming growth factor (TGF) alpha led to a mutant protein with dramatically altered biological activities. Lazar et al. stated that they ‘did not expect that a mutation of Leu to Ile (which have similar sizes and polarities) would cause such a strong effect’. See paragraph bridging left and right columns on page 1251; and third full paragraph on page 1251. Furthermore, the art recognizes that defining epitopes is not easy and there is a confusing divergence between the textbook definition of epitope and the definition that is in use in published descriptions of experimental investigations and that epitopes must be empirically determined. See Greenspan et al., Nature Biotechnology 17:936-937, 1999. Given this art-recognized functional unpredictability and the lack of structure-function correlation for the entire variant genus in the instant case, a skilled artisan cannot immediately envision or recognize at least a substantial number of members of the claimed genus of polypeptide variants, each having the requisite prophylactic and therapeutic vaccine function(s) in vivo in a subject. The specific domains or regions, or the specific linear and/or conformational epitopes within SEQ ID NO: 3 that are required for and correlated with the therapeutic and prophylactic vaccine function(s) in vivo in a subject are not disclosed, without which one of skill in the art cannot envision or produce at least 80% identical variant species of SEQ ID NO: 13 or 15 that retain such domains, regions, or epitopes intact and also retain the required vaccine functions against S. aureus infections. A convincing structure-function correlation for the entire polypeptide variant genus is lacking. Clearly, Applicants did not describe the invention of the instant claims sufficiently to show that they had possession of the full scope of the method as claimed at the time of the invention. Faridmoayer et al (WO 2019/12196) teach that bioconjugates of S. aureus with P. aeruginosa EPA or S. aureus ClfA as a carrier protein have been described and while they produced opsonic antibodies in vitro they failed to or have yet to demonstrate prophylaxis (see page 2, first paragraph). The instant specification does not provide evidence that a conjugate or bioconjugate provides for therapeutic or prophylactic efficacy.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. MPEP § 2163.02 states: ‘an objective standard for determining compliance with the written description requirement is, does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed’. The courts have decided that the purpose of the ‘written description’ requirement is broader than to merely explain how to ‘make and use’; the Applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed. See Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991). Furthermore, the written description provision of 35 U.S.C § 112(a) or 35 U.S.C § 112(pre-AIA ), first paragraph is severable from its enablement provision. The written description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-373 (Fed. Cir. 1984) (affirming rejection because the specification does ‘little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.’). The essence of the written description requirement is that a patent applicant, as part of the bargain with the public, must describe his or her invention so that the public will know what it is and that he or she has truly made the claimed invention. See Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., 535 U.S. 722, 736 (2002) (“The requirements must be satisfied before issuance of the patent, for exclusive patent rights are given in exchange for disclosing the invention to the public. What is claimed by the patent application must be the same as what is disclosed in the specification . . . .” (internal citations omitted)); O’Reilly v. Morse, 56 U.S. 62, 120–21 (1853) (“The evil is the same if he claims more than he has invented, although no other person has invented it before him. He prevents others from attempting to improve upon the manner and process which he has described in his specification and may deter the public from using it.”). We have explained that “requiring a written description of the invention plays a vital role in curtailing claims . . . that have not been invented, and thus cannot be described.” Ariad, 598 F.3d at 1352. “For generic claims, we have set forth a number of factors for evaluating the adequacy of the disclosure, including ‘the existing knowledge in the particular field, the extent and content of the prior art, the maturity of the science or technology, [and] the predictability of the aspect at issue.” Id. (quoting Capon v. Eshhar, 418 F.3d 1349, 1359 (Fed. Cir. 2005)). For the reasons delineated supra, one skilled in the art would not recognize from the as-filed disclosure that Applicants were in possession of the broad polypeptide variant genus, and the full scope of the invention as claimed at the time the application was filed. Instant claims do not meet the written description provision of 35 U.S.C § 112(a) or (pre-AIA ) first paragraph.
Double Patenting
The USPTO may not institute a derivation proceeding in the absence of a timely filed petition. The U.S. Patent and Trademark Office normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). The applicant should amend or cancel claims such that the applications no longer contain claims directed to the same invention.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 11, 13 and 48-51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 9 and 10 of U.S. Patent No. 11,819,544. Although the claims at issue are not identical, they are not patentably distinct from each other because bioconjugates of variants of ClfA of S. aureus of SEQ ID NO:3 (equivalent to SEQ ID NO:10, 11 or 12 herein) modified with consensus sequence SEQ ID NO:23 or 24 therefore anticipates the instant claims when Z=0.
Claims 11, 13 and 48-51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16-18 of U.S. Patent No. 11,286,283 in view of Anderson et al (Human Vaccines & Immunotherapeutics 8(11):1585-1594, 2012). Although the claims at issue are not identical, they are not patentably distinct from each other because the bioconjugates of Hla of S. aureus of SEQ ID NO:1 (patent claim 1) encompass those modified with consensus sequence SEQ ID NO:12 (of patent dependent claim 3; where Z=0) and the bioconjugates produced by the methods comprising a bioconjugate linked to a saccharide and the Hla protein having SEQ ID NO:12. ‘283 differs by not linking S. aureus capsular polysaccharide 5 or 8 to the modified Hla having SEQ ID NO:12.
Anderson et al teach conjugates of serotypes 5 and 8 to other carrier proteins (see page 1587, column 2, first paragraph), including those from S. aureus (i.e. ClfA)
It would have been prima facie obvious to one having ordinary skill in the art to bioconjugate serotype 5 or 8 capsular polysaccharide to the modified S. aureus Hla of the ‘283 patent comprising the glycosylation site of SEQ ID NO:12 where Z=0 because Anderson et al teach that conjugates can provide for an opsonophagocytic antibody response important for a potential vaccine. In the absence of evidence to the contrary it is prima facie obvious to substitute one carrier protein for another as they are known function equivalently to provide T cell help to polysaccharide antigens.
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.
Claims 11-15 and 47-51 are rejected under 35 U.S.C. 102(a)1 and 102(a)(2) as being clearly anticipated by Braun et al (WO 2019/121924 published June 27,2019 with priority to December 21, 2017).
Braun et al teach consensus glycosylation sequence K-D/E-X-N-Z-S/T-K where X and Z are any amino acid except proline (see page 3, lines 15-20) and exemplifies KDQNRTK (SEQ I DNO:23 at page 15). Braun et al teach a modified Hla protein (Staphylococcus aureus haemolysin A/alpha toxin having SEQ ID NO:3 comprising the glycosite see page 3) and conjugates of the modified HLA including bioconjugates (see page 3, lines 21-24; page 16, lines 6-19). The consensus glycosylation sequence meets the claimed invention where the instantly claimed “Z”=0. Figure 3, demonstrate CP5 (serotype 5 capsular saccharide of S. aureus) linked to HLA (see page 6, Figure 3 description). The HLA and the CP5 are from the same microorganism (S. aureus). Braun et al teach conjugates of the modified protein by lysine, tyrosine, histidine, arginine, tryptophan (see pages 23-25) either by direct or indirect coupling. Polysaccharide antigens for coupling are enumerated at page 27 and claims 19-49 at pages 87-91). The HLA protein (SEQ ID NO:1) and modified HLA protein (SEQ ID NO:3) are greater that 80% identical as compared to SEQ ID NOS:14, 15 and 16 of the instant application .Braun et al teach the use of the conjugates as vaccines (see claims and description). Braun et al anticipate the instantly claimed invention.
Claims 11-15 and 47-51 are rejected under 35 U.S.C. 102(a)1 and 102(a)(2) as being clearly anticipated by Faridmoayer et al (WO 2019/121926 published June 27,2019 with priority to December 21, 2017).
Faridmoayer et al teach consensus glycosylation sequence K-D/E-X-N-Z-S/T-K where X and Z are any amino acid except proline (see page 2, last paragraph) and exemplifies KDQNRTK (SEQ I DNO:23 at page 15). Faridmoayer et al teach a modified ClfA protein (Staphylococcal aureus clumping factor/ClfA having SEQ ID NO:3 comprising a PglB glycosite see pages 2-3) and conjugates of the modified ClfA including bioconjugates (see page 4, lines 11-14; page 8, Figures 7 and 8 description). The consensus glycosylation sequence meets the claimed invention where the instantly claimed “Z”=0. Figure 3, demonstrate CP8 (serotype 5 capsular saccharide of S. aureus) linked to ClfA(see page 6, Figure 3 description). The HLA and the CP8 are from the same microorganism (S. aureus). Faridmoayer et al teach the invention may comprise multiple consensus sequences (see page 18, last paragraph). Faridmoayer et al teach conjugates of the modified protein by lysine, tyrosine, histidine, arginine, tryptophan (see pages 21-24) either by direct or indirect coupling. Polysaccharide antigens for coupling are enumerated at page 25). The ClfA protein (SEQ ID NO:1) and modified HLA protein (SEQ ID NO:3) are greater that 80% identical as compared to SEQ ID NOS:10, 11 and 13 of the instant application. Faridmoayer et al contemplate the use of the bioconjugates as vaccines (see page 45). Faridmoayer et al anticipate the instantly claimed invention.
Conclusion
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/Patricia Duffy/Primary Examiner, Art Unit 1645