DETAILED ACTION
Election/Restrictions
Applicant’s election of Group II, claims 11-22 and the Species: a polynucleotide sequence encoding a Gmd polypeptide fragment comprising: the amino acid sequence of SEQ ID NO: 22 (e.g., the nucleic acid sequence of SEQ ID NO:23 and the RNA sequence of SEQ ID NO:24), or an immunogenic variant or fragment thereof (disclosed in claim 14(e)(1)), in the reply filed on 12/19/25 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 11-14, 16-18 and 20-22 read upon the elected species.
Claims 1-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.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 11-22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 11-22 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of the different polynucleotides/polypeptides, e.g., Atl, CHIPs, SEQ ID NOS: 1-102, etc., is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: these polynucleotides are structurally different with different nucleic acid sequences that elicit different immune responses which have differing abilities to treat and/or prevent disease. They do not share a “structural similarity and the same common use.
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 11 is vague and indefinite because it recites a method which uses in undefined nucleic acid described only that it encodes a “S. aureus antigenic polypeptide, immunogenic variant or fragment thereof.” The mere recitation of a name, e.g., a nucleic acid encoding a S. aureus polypeptide, fragment, variant thereof, etc., to describe the invention is not sufficient to satisfy the Statute's requirement of adequately describing and setting forth the inventive concept. Further, this description encompasses a huge amount of structures and the claim does not provide any information to adequately define the nucleic acid being claimed. The claim should provide any structural properties, such as the nucleic sequence or the amino acid that the nucleic sequence encodes, which would allow for one to identify the nucleic acid to be used in the method without ambiguity. The mere recitation of a name does not adequately define the nucleic acid in the claimed method. 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 11 is also vague and indefinite due to the terms “immunogenic variant or fragment thereof.” A fragment reads on as few as one amino acid and it is unclear what is encompassed by a “variant thereof.” The metes and bounds of the phrase are not understood. Also, is this a functional variant, a structural variant, etc. 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 13 is vague and indefinite due to the phrase “a substituted polynucleotide” and “codon optimized” for expression in cells of a mammal. The metes and bounds of these phrases are not understood. The claim does not make clear what is substituted or how much of the polynucleotide is substituted or even provide a sequence for the ‘unsubstituted’ structure. Additionally, it is unclear what the ‘codon-optimized’ sequence looks like. 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 13 is also vague and indefinite for the parentheticals in part (c ) of the claim. The “e.g.,” (for example), also makes it unclear if these are claim limitations. In patent claims, the use of parentheses is generally not allowed. If parentheses are necessary, they should be used sparingly an only to include information that is not part of the technical features of the claim. Claims should be drafted to clearly define the scope of the invention and to avoid ambiguity. Appropriate clarification and/or correction is required.
Claim 14 e(i) is vague and indefinite for the parentheticals in the claim. The “e.g.,” (for example), also makes it unclear if these are claim limitations. In patent claims, the use of parentheses is generally not allowed. If parentheses are necessary, they should be used sparingly an only to include information that is not part of the technical features of the claim. Claims should be drafted to clearly define the scope of the invention and to avoid ambiguity. Appropriate clarification and/or correction is required.
Claim 14 is also vague and indefinite due to the terms “immunogenic variant or fragment thereof.” A fragment reads on as few as one amino acid and it is unclear what is encompassed by a “variant thereof.” The metes and bounds of the phrase are not understood. Also, is this a functional variant, a structural variant, etc. 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 19 is vague and indefinite due to the terms “immunogenic variant or fragment thereof.” A fragment reads on as few as one amino acid and it is unclear what is encompassed by a “variant thereof.” The metes and bounds of the phrase are not understood. Also, is this a functional variant, a structural variant, etc. 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 Objections
Claims 11,12 and 15 are objected to because of the following informalities:
Claim 11 should be amended to include the material from the non-elected claims which it depends.
Claim 12 recites non-elected polynucleotides/peptides.
Claim 15 is drawn to a non-elected species solely.
Claim 19 is drawn to a non-elected species solely, e.g., a method of administering a polypeptide.
Appropriate correction is required.
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 11-14, 16-18 and 20-22 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 claims are drawn, for example, to:
11. A method for inducing an antigen specific immune response against Staphylococcus aureus in a subject, comprising administering to the subject composition comprising a nucleic acid encoding an antigenic polypeptide, immunogenic variant or fragment thereof that corresponds to Gmd (elected polypeptide) in an amount effective to produce an antigen specific immune response.
The method of claim 11 wherein the method treats or prevents S. aureus infection.
The method of claim 11 wherein the method treats or prevents one or more disease or disorder associated with S. aureus infection.
The method wherein the disease or disorder is osteomyelitis.
To fulfill the written description requirements set forth under 35 USC § 112, first paragraph, the specification must describe at least a substantial number of the members of the claimed genus, or alternatively describe a representative member of the claimed genus, which shares a particularly defining feature common to at least a substantial number of the members of the claimed genus, which would enable the skilled artisan to immediately recognize and distinguish its members from others, so as to reasonably convey to the skilled artisan that Applicant has possession the claimed invention. Applicants have not described the genus of antigens to be used in the claimed methods such that the specification might reasonably convey to the skilled artisan that Applicants had possession of the claimed invention at the time the application was filed.
The term Gmd polypeptide and any immunogenic variants or fragments thereof is not full supported. Claim 14 does recite that the polypeptide fragment may comprise the amino acid of SEQ ID NO: 22; however, It is unclear what structures are encompassed by variants or fragments thereof and what part of the structure would need to be retained to possess the functional element of the instant claims.
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).
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 itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. The Guidelines for Examination of Patent Applications Under the 35 U.S.C. 112, paragraph 1, "'Written Description" Requirement (66 FR 1099-1111, January 5,2001) state, "[p]ossession may be shown in a variety of ways including description of an actualreduction to practice, or by showing the invention was 'ready for patenting' such asby disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention" (Id. at 1104). Moreover, because the claims encompass a genus of variant species, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was "ready for patenting" by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed. The Guidelines further state, "[f]or inventions in an unpredictable art, adequatewritten description of a genus which embraces widely variant species cannot beachieved by disclosing only one species within the genus'" (Id. at 1106);accordingly, it follows that an adequate written description of a genus cannot beachieved in the absence of a disclosure of at least one species within the genus. Asevidenced by Greenspan et al (Nature Biotechnology 7: 936-937, 1999), definingepitopes is not as easy as it seems. Greenspan et al recommends defining anepitope by the structural characterization of the molecular interface between theantigen and the antibody is necessary to define an "epitope" (page 937, column 2).According to Greenspan et al, an epitope will include residues that make contactswith a ligand, here the antibody, but are energetically neutral, or even destabilizingto binding. Furthermore, an epitope will not include any residue not contacted by the antibody, even though substitution of such a residue might profoundly affectbinding. There is a limit to how much substitution can be tolerated before the originaltertiary structure is lost. Therefore, absent a detailed and particular description of arepresentative number, or at least a substantial number of the members of thegenus of fragments or variants of the eleven peptides, the skilled artisan could notimmediately recognize that Applicants were in possession of the claimed genus ofpeptides at the time of filing.
The scope of the claim includes numerous structural variants (i.e. fragments), and the genus is highly variant because a significant number of structural differences between genus members is permitted. The specification does not describe any members of the claimed genus by complete structure. One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus, and thus, that the applicant was not in possession of the claimed genus. The claimed subject matter is not supported by an adequate written description because a representative number of species has not been described.
There are no drawings or structural formulas disclosed of any of thesefragments or variants of the Gmd polypeptide. There is no teaching in thespecification regarding which part of the structure can be varied and still produce a polypeptide which has functional activity.
Based on the lack of knowledge and predictability in the art, those of ordinaryskill in the art would not conclude that the applicant was in possession of theclaimed genus of peptides to be used in the claimed method based on disclosure of the single species of SEQ ID NO: 22.
Claim Rejections - 35 USC § 112-Scope of Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 11-14, 16-18 and 20-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
A method of inducing an immune response to Staphylococcus aureus comprising administering a polynucleotide sequence encoding a Gmd polypeptide comprising SEQ ID NO: 22,
does not reasonably provide enablement for the full breadth of the claims, for example, to:
11. A method for inducing an antigen specific immune response against Staphylococcus aureus in a subject, comprising administering to the subject composition comprising a nucleic acid encoding an antigenic polypeptide, immunogenic variant or fragment thereof that corresponds to Gmd (elected) in an amount effective to produce an antigen specific immune response.
The method of claim 11 wherein the method treats or prevents S. aureus infection.
The method of claim 11 wherein the method treats or prevents one or more disease or disorder associated with S. aureus infection.
The method wherein the disease or disorder is osteomyelitis.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The specification states that substitutions, additions, or deletions, may be made to the defined sequences; however, the specification provides no guidance as which nucleic acids may be changed without causing a detrimental effect to the polypeptide it encodes and the functional requirements in the claims. It is unpredictable as to which nucleic acids/amino acids could be removed and which could be added. While it is known that many amino acid substitutions are possible in any given protein, the position within the protein’s sequence where amino acid substitutions can be made with a reasonable expectation of success are limited. Other positions are critical to the protein’s structure/function relationship, e.g., such as various positions or regions directly involved in binding, catalysis in providing the correct three-dimensional spatial orientation of binding and catalytic sites. These regions can tolerate only very little or no substitutions. Selective point mutation to one key residue could eliminate the function of the polypeptide. It could eliminate its functional properties. If the range of decreased binding ability after single point mutation of a protein antigen varies, one could expect point mutations in the protein antigen to cause varying degrees of loss of protection/function, depending on the relative importance to the binding interaction of the altered residue. Alternatively, the combined effects of multiple changes, as instantly claimed, in an antigenic determinant could again result in loss of function. A protein having multiple point mutations, or accumulated point mutations at key residues could create a new antigen that is precipitously or progressively unrecognizable. As stated above, Applicants have not shown the particular substitution and the result it produces. Applicants have provided no guidance to enable one of ordinary skill in the art how to determine, without undue experimentation, the effects of different amino substitutions and the nature and extent of the changes that can be made
It is expensive and time consuming to make amino acid substitutions at more than one position, in a particular region of the protein, in view of the many fold possibilities for change in structure and the uncertainty as to what utility will be possessed. See Mikayama et al. (Nov.1993. Proc.Natl.Acad.Sci. USA, vol. 90 : 10056-10060) which teaches that the three-dimensional structure of molecules is important for their biological function and even a single amino acid difference may account for markedly different biological activities. Amino acids owe their ‘significance’ to their inclusion in a pattern which is directly involved in recognition by, and binding to, the receptor and the significance of the particular amino acids and sequences for different amino acids cannot be predicted a priori, but must be determined from case to case by painstaking experimental study. The instant claims allow for substitutions with amino acids of vastly different properties and they do not recite the specific changes in the claims.
Additionally, claims 20-22 recite that the methods prevent S .aureus infection, or prevents one or more disease or disorders associated with S. aureus infection, including osteomyelitis. Vaccines induce protection against infections by stimulating the development of long-lived effector cells and memory cells (Abbas et al. Cellular and Molecular Immunology 4th edition chapter 15 p. 360-362, 2000). Vaccines by definition trigger an immunoprotective response in the host vaccinated and mere antigenic response i.e. immunogenicity is insufficient. It is well recognized in the vaccine art, that it is unclear whether an antigen(s) derived from a pathogen will elicit protective immunity. Ellis, R.W. (Chapter 29 of "VACCINES" [PIotkin, S.A. et al. (eds) published by W. B. Saunders company (Philadelphia) in 1988, especially page 571, 2nd full paragraph] exemplifies this problem in the recitation that "The key to the problem (of vaccine development) is the identification of that protein component of a virus or microbial pathogen that itself can elicit the production of protective antibodies ....and thus protect the host against attack by the pathogen".
Sherchand et al (Front. Cell. Infect. Microbiol., 17 July 2022. Vol 12, pp. 1-9. Sec. Bacteria and Host). Staphylococcus aureus osteomyelitis remains a very challenging condition; recent clinical studies have shown infection control rates following surgery/antibiotics to be ~60%. Additionally, prior efforts to produce an effective S. aureus vaccine have failed, in part due to lack of knowledge of protective immunity.
Miller at al (FEMS Microbiol Rev. 2019 Dec 16;44(1):123–153) studies the evasion mechanisms of S.aureus and discloses that all vaccination attempts aimed at preventing S. aureus invasive infections have failed in human trials, especially all vaccines aimed at generating high titers of opsonic antibodies against S. aureus surface antigens to facilitate antibody-mediated bacterial clearance. The review summarizes the data from humans regarding the immune responses that protect against invasive S. aureus infections as well as host genetic factors and bacterial evasion mechanisms, which are important to consider for the future development of effective and successful vaccines and immunotherapies against invasive S. aureus infections in humans. The evidence presented form the basis for a hypothesis that staphylococcal toxins (including superantigens and pore-forming toxins) are important virulence factors, and targeting the neutralization of these toxins are more likely to provide a therapeutic benefit in contrast to prior vaccine attempts to generate antibodies to facilitate opsonophagocytosis. Kates et al (J Bone Joint Surg Am. 2020 Nov 4;102(21):1842-1848) teaches that to date, 19 S. aureus immunizations have been evaluated in U.S. Food and Drug Administration registration trials, and all failed to demonstrate efficacy. Expert opinion on the root cause of these failures has focused on the inability to predict the protective role of staphylococcal immune responses in humans based on animal data. S. aureus bone infections are caused by pathogenic mechanisms that have developed to achieve immune evasion. Mechanisms include (1) biofilm formation on the implant and necrotic bone , (2) generation of staphylococcal abscess communities in soft tissues and bone marrow, (3) intracellular infection, and (4) ability to colonize the osteocytic-canalicular network of live cortical bone. Persistence of infection following surgical treatment of S. aureus osteomyelitis is common (15% to 40%) and often requires multiple surgeries.
Immunogenicity does not predict a protective immune response. Additionally, there are no working examples in the instant specification to guide the skilled artisan in practicing the claimed method. There are no other examples of delivery of any other therapeutic agent present in the specification. Genentech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 clearly states: “Patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable. See Brenner v. Manson, 383 U.S. 519, 536, 148 USPQ 689, 696 (1966) (stating, in context of the utility requirement, that "a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.") Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.”
There are no results for immunization experiments or challenge experiments with the composition recited in the instant claims.
Given the inherent unpredictability of preventive vaccines for S. aureus, and more particularly osteomyelitis, it would take one skilled in the art undue experimentation to make and/or use the invention.
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) 11-14, 16, 18, 20-22 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Moeller et al (WO 2012/136653; provided by Applicants).
Moeller et al discloses a composition for inducing an immune response against Staphylococcus aureus (S. aureus) in a subject, the composition comprising one or more nucleic acid molecules encoding one or more S. aureus antigenic polypeptide (SEQ ID NO: 1), immunogenic variant or fragment thereof (claims 1, 29-41, 50, 53; SEQ ID NO: 8). Moeller et al discloses the nucleic acid being a mRNA (page 9, lines 7-9; page 18, lines 17, 18; claim 30, claim 53). With respect to 18, Moeller discloses the nucleic acid encapsulated by a lipid nanoparticle (page 32, line 15). Moeller discloses the nucleic acid being contained in a vector (page 32, line 6; claims 34-41, 50, 53, 76). Moeller discloses the composition comprising an adjuvant (claim 50, 52, 53). With respect to claim 22: Moeller discloses osteomyelitis as the disease being treated (page 2, paragraph 2 (object of the invention)). It is noted that the claims allow for any nucleic acid encoding any one or more S.aureus antigenic, polypeptides, immunogenic variants or fragments thereof. Additionally, even claim 14 which recites the amino acid and nucleic acid sequence for Gmd, also allows for any immunogenic variant or fragment thereof.
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) 13 and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Moeller et al (WO 2012/136653; provided by Applicants) in view of Huang et al (WO 2018/081459; provided by Applicants).
The teachings of Moeller et al are set forth above. Moeller: A composition for inducing an immune response against Staphylococcus aureus (S. aureus) in a subject, the composition comprising one or more nucleic acid molecules encoding one or more S. aureus antigenic polypeptide (SEQ ID NO: 1), immunogenic variant or fragment thereof (claims 1, 29, 50, 53; SEQ ID NO: 8). Moeller further discloses that the nucleic acid is encapsulated by a lipid nanoparticle (page 32, line 15) or that the nucleic acid is contained in a vector (page 32, line 6; claims 34-41, 50, 53, 76). The subject-matter of claim 13 therefore differs from this known composition in that the nucleic acid is (i) a polynucleotide sequence that does not occur in nature; (ii) a polynucleotide sequence codon optimized for expression in cells of a mammalian subject; and (iii) a modified nucleoside; The technical effect associated with said difference is masking the inflammatory nature of an exogenous RNA. The problem to be solved by the present invention may therefore be regarded the provision of RNA which is modified by for example similar nucleosides not occurring in nature. To replace a natural occurring nucleoside for example uridine by pseuouridine falls is a well-known technique for the person skilled in the art in order to mask the inflammatory nature of an exogenous RNA. See for example Huang et al in claims 16, 29, 94-97. Huang et al discloses a composition for inducing an immune response against Staphylococcus aureus (S. aureus) in a subject, the composition comprising one or more nucleic acid molecules encoding one or more S. aureus antigenic polypeptide (SEQ ID NO: 1), immunogenic variant or fragment thereof (page 9, paragraph 3 to page 12, paragraph 2; E256, E279; E291 to E296). Therefore, the subject matter of claim 13 is obvious in view of Huang et al. With respect to claim 17 it is common practice of a person skilled in the art to use a mRNA comprising a 5' untranslated (UTR) region, an open reading frame, and a 3' UTR and a polyA tail. Only exemplarily it is referred to Huang (page 10, lines 10-14; page 65, paragraph 3). Accordingly, it would have been prima facie obvious given the teachings of Huang to provide an immunogenic composition against S. aureus. In addition, it should be noted, that the examples of the present application do not show any improvement or effect of any specific composition in the claimed methods. In the absence of facts and data which would be suitable to demonstrate any unexpected effects and/or properties of presently claimed composition comprising an S. aureus antigenic polypeptide when compared to those already described in the prior art the presence of an inventive step cannot be acknowledged as the provision of further compositions using methods well- known in the art cannot be considered to be inventive.
Status of Claims
No claims are presently allowed.
The full-length sequences set forth in SEQ ID NOS: 23 and 24, as elected in the Species requirement, e.g., claim 14, part (i), are free of the prior art.
SEQ ID NO: 22 is taught in the prior art, for example, see:
Schwarz et al (US Patent No. 9737601) and (WO 2011/40114) teach S. aureus glucosaminidase SEQ: 36 which is 100% identical to Applicants’ SEQ ID NO: 22. See sequence alignment in Public PAIR/supplemental content tab. Title: ANTI-GLUCOSAMINIDASE PASSIVE IMMUNIZATION FOR STAPHYLOCOCCUS
SEQ ID NO 71 of Castado et al (WO 2006/032475) is 100% identical to Applicants’ SEQ ID NO: 22. See sequence alignment in Public PAIR/supplemental content tab. Immunogenic composition, useful to prevent or treat staphylococcal infection.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jennifer E. Graser whose telephone number is (571) 272-0858. The examiner can normally be reached on Monday-Friday from 8:00 AM-4 PM.
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/JENNIFER E GRASER/ Primary Examiner, Art Unit 1645 2/13/26