DETAILED ACTION
Acknowledgment and entry of the Amendment submitted on 5/12/26 is made.
Applicants previously elected Group I, claims 1, 4-14; for claim 10- the Species ABC transporter (PsaA), in the reply filed on 11/7/25.
Claims 2, 3 and 15-21 remain withdrawn from consideration for being drawn to a non-elected invention.
Claims 4-14 were previously objected to for having improper multiple dependencies and were not further treated on their merits. Any rejections set forth below to claims 4-14 were necessitated by the amendment to the claims to correct the improper multiple dependencies.
Applicants’ arguments are rendered moot in view of the new grounds of rejection set forth below which were necessitated by the amendments to the claims.
Claim Rejections - 35 USC § 112-2nd paragraph
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1 and 4-14 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 1 and 5 are vague and indefinite because it is unclear what structures are encompassed by the term “immunologically effective analog of the sequence or fragment thereof.” What is an analog and what structure does it comprise. An analog does not reveal the structure that is claimed. The metes and bounds of this term are not understood. Additionally, an immunologically effective fragment [of the proteins recited therein] is vague and indefinite considering that the examples only of the instant specification concern full-length proteins or defined fragments, and considering that the meaning of "immunogically effective" does not define how and to which extent the fragment should be "immunologically effective", the term "immunogically effective fragment" is not clear, 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 one to identify what is being claimed. Further, the last sentence recites “wherein an effective amount of each protein is used…” and this is unclear if “protein” is intended to just encompass the full-length sequences or also any immunogenic fragments and/or analogs’ as well. Appropriate clarification and/or correction is required.
Claim 10 is 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 a laundry list of potential additional antigenic determinants of vastly different structures and sources 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:
It is well known in the prior art that combination/multivalent vaccines are highly unpredictable. Reduced immunogenicity can occur when multiple antigens are delivered as mixtures on the same or similar carrier proteins. In the latter situation, the immune system can become overloaded, resulting in an impaired response to any vaccine component. The combination of several different antigens into a single multivalent injection may result in competition among the different components and adversely affect the immunogenicity of any individual component. These immunogenic compositions comprising vastly different members do not share a structural similarity, nor produce the same immunogenic effect.
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 (elicit the same immune response).
Claim 14 is vague and indefinite because it is unclear what is encompassed by “includes one or more of the features of claims 6 to 12.” What features is this in reference too? Claims 6-10 have vastly different “features.” The metes and bounds of the claim cannot be understood. 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 1 and 4-14 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims recite compositions which may comprise immunologically effective analogs of immunogenic fragments or proteins comprising SEQ ID NO: 1, 2 or 3.
The claim encompasses protein analogs that perform a similar function to the proteins of SEQ ID NOS: 1, 2 or 3, but that have a different evolutionary origin. For example, two enzymes from different species may catalyze the same chemical reaction but have entirely different amino acid sequences and structural origins. In other words, a protein analog is defined by functional equivalence, and the instant specification does not provide written support for these analogs and their structures are not described.
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 claimed analogs and fragments 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.
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 [product] itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was 'ready for patenting' such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention" (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. 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." In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). To satisfy the written description requirement, an 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, and that the invention, in that context, is whatever is now claimed. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991) and MPEP 2163.02.
However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was "ready for patenting" by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus'" (Id. at 1106); accordingly, it follows that an adequate written description of a genus cannot be achieved in the absence of a disclosure of at least one species within the genus. The scope of the claim includes numerous structural variants, and the genus is highly variant because a significant number of structural differences between genus members is permitted.
One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus, 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.
Because the art is unpredictable, in accordance with the Written Description Guidelines, the recitation of "an effective analogs” or fragments thereof is not adequate. The scope of the claim includes numerous structural variants, 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 claimed polynucleotides. There is no teaching in thespecification regarding which part of the structure can be varied and still produce a polypeptide which has at least two of the recited immunogenic activities, nor is there description of sequences of any “analogs”. Based on the lack of knowledge and predictability in the art, those of ordinary skill in the art would not conclude that the applicant was in possession of the claimed genus of antigenic determinants.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov
Claim Rejections - 35 USC § 112-Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1 and 4-14 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:
An immunogenic composition comprising at least two Streptococcus pneumoniae proteins selected from the group consisting of: ABC-T comprising the amino acid of SEQ ID NO: 1, PavA comprising the amino acid of SEQ ID NO: 2; and ZmpB comprising the amino acid sequence of SEQ ID NO: 3, (and also with PspA in claim 10)
does not reasonably provide enablement for
An immunogenic composition comprising at least three antigenic determinants, wherein the antigenic determinants are derived from at least two proteins selected from ABC-T, PavA and ZmpB of a Streptococcus pneumoniae bacterium, and wherein; the antigenic determinant derived from ABC-T comprises the protein sequence SEQ ID NO:1, or an immunologically effective fragment thereof or an immunologically effective analog of the sequence or fragment thereof;
the antigenic determinant derived from PavA comprises the protein sequence SEQ ID NO:2, or an immunologically effective fragment thereof or an immunologically effective analog of the sequence or fragment thereof; and
the antigenic determinant derived from ZmpB comprises the protein sequence SEQ ID NO:3, or an immunologically effective fragment thereof or an immunologically effective analog of the sequence or fragment thereof; and wherein an effective amount of each protein is used such that the immunogenic composition elicits an immune response when administered to a mammal.
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 instant claims recite compositions which may comprise immunologically effective analogs of “effective” immunogenic fragments or proteins comprising SEQ ID NO: 1, 2 or 3. Claim 10 also recites a laundry list of numerous additional antigenic determinants which may be included in the compositions. The instant specification is not enabled for this scope of invention.
The specification states that substitutions, additions, or deletions, may be made to the defined sequences; however, the specification provides no guidance as which amino acids may be changed without causing a detrimental effect to the immunogenic composition. It is unpredictable as to which 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. Rudinger et al. (June 1976. Peptide Hormones. Biol.Council. pages 5-7) also teaches that 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, the claims encompass protein analogs that perform a similar function to the proteins of SEQ ID NOS: 1, 2 or 3, but that have a different evolutionary origin. For example, two enzymes from different species may catalyze the same chemical reaction but have entirely different amino acid sequences and structural origins. In other words, a protein analog is defined by functional equivalence, and the instant specification does not enable these analogs as their structures are not described. 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.”
With respect to the language “an immunologically effective fragment [of the proteins recited therein]”, considering that the examples in the instant specification only concern full-length proteins or defined fragments, and considering that the meaning of "immunologically effective" does not define how and to which extent the fragment should be "immunologically effective", the term "immunologically effective fragment" is not enabled. The specification fails to provide enablement for “immunologically effective fragments” of any of the proteins or their analogs. Additionally, an immunogenic fragment can read on as few as a couple of amino acids to many more. The specification does not enable these particular fragments and their use in combination with other antigens.
Additionally, with respect to claim 10, for example, it is well known in the prior art that combination/multivalent vaccines are highly unpredictable. Reduced immunogenicity can occur when multiple antigens are delivered as mixtures on the same or similar carrier proteins. In the latter situation, the immune system can become overloaded, resulting in an impaired response to any vaccine component. The combination of several different antigens into a single multivalent injection may result in competition among the different components and adversely affect the immunogenicity of any individual component. See Fattom et al. Vaccine Vol. 17, Number 2, January 1999, pp. 126-133(8) and NIH GUIDE, Volume 22, Number 28, Multicomponent Vaccine Development, August 6, 1993. The instant specification has not provided results with any of the multitude of combination vaccines recited in instant claims 6-10. Given the inherent unpredictability of combination vaccines combined with the very large and divergent group of antigens recited in claims 6-10, it would take one skilled in the art undue experimentation to make and/or use the invention.
Accordingly, 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.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1 and 4-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Malley et al (WO 2014/124228; published 8/14/2014- provided by Applicants), Rappouli et al (WO2011030218-A1), Camilli et al (WO2004020609-A2; provided by Applicants), (Le Page et al WO200279241-A2; provided by Applicants) in view of Yibing et al (CN 109456393; provided by Applicants) and Yi et al (Infect. Immun. 79(2): 867-868. Feb. 2011; provided by Applicants), Houston et al (WO 2005/113602; provided by Applicants) and further in view of Basavanna, S. ("Screening of streptococcus pneumoniae ABC transporters for their role in virulence and investigation of their lipoprotein components as vaccine candidates", 28 November 201. Nov. 2011; provided by Applicants), Jomma et al (Vaccine. 24(24): 5133-5139. June 2006; provided by Applicants) and Franziska (: "Immunogenicity and protectivity of surface-localized lipoproteins of Streptococcus pneumoniae", 18 December 2018. Pages 1-251; provided by Applicants).
Malley is directed to novel pneumococcal polypeptide antigens and nucleic acids encoding such antigens, and immunogenic compositions comprising such antigens for treating and preventing pneumococcal infection. The present invention further provides method of using the antigens to elicit an immune response (e.g., IL-17A response, a T cell-mediated and/or B-cell-mediated immune responses). The present invention also provides methods of prophylaxis and/or treatment of pneumococcal-mediated diseases, such as sepsis, comprising administering an immunogenic composition including one or more of a combination of pneumococcal antigens or functional fragments thereof as disclosed herein. In some embodiments, one or more pneumococcal antigens can be present in a polysaccharide conjugate. The compositions induce an anti-pneumococcal immune response when administered to a mammal. The compositions can be used prophylactically to vaccinate an individual and/or therapeutically to induce a therapeutic immune response to an infected individual.
See paragraph [0126], claim 10, and Table 1, pages 27, 30 and 31.
[00126] pneumococcal antigens as described herein may be used in conjunction with other pneumococcal antigens such as those known in the art, such as those disclosed in US patent WO/2000/037105, 7,217,791 and 7,585,669, US2006/0121058, US2012/0251577, US2011/0159040, US2012/0189649, and US20110020386 which are incorporated herein in their entirety by reference. Other appropriate S. pneumoniae antigens for combination vaccines include Pneumococcal surface protein A (PspA); derivatives of PspA, Choline-binding protein A (CbpA) and derivatives thereo ; Pneumococcal surface adhesin A (PsaA); caseinolytic protease; sortase A (SrtA); pilus 1 RrgA adhesin; PpmA; PrtA; PavA; LytA; Stk-PR; PcsB; RrgB and derivatives thereof. For further details, see, e.g., A.D Ogunniyi et al., "Protection against Streptococcus pneumoniae elicited by immunization with pneumolysin and CbpA," Infect Immun. 2001 October; 69 (10):5997-6003; which is incorporated by reference herein in its entirety.
Claim 10. The immunogenic composition of any of paragraphs 1 to 9, wherein the immunogenic composition comprises at least 3 pneumococcal antigens or fragments with the amino acid sequence selected from SEQ ID NO: 1-76 or SEQ ID NO: 153-234.
Paragraphs [0142]-[0184] describe the use of adjuvants.
[00109] Table 1. Table 1 lists the amino acid sequence identification numbers of the pneumococcal immunogens. The amino acid sequences and nucleotide sequences of the pneumococcal antigens are available on world-wide web site: "xbase.ac.uk/genome/streptococcus-pneumoniae- tigr4/NC_003028/features?page=1", which is incorporated herein in its entirety by reference. Table 1: SP0620 recites ABC-transporter protein; SEQ ID NO: 25; SP0453 ABC-transporter protein SEQ ID NO: 17; SP0664 zinc metalloprotease ZmpB SEQ ID NO: 29; SP1386 recites ABC-transporter protein SEQ ID NO: 46; SP1500 ABC-transporter protein SEQ ID NO: 51; SP1683 ABC-transporter protein SEQ ID NO: 56; SP1826 ABC-transporter protein SEQ ID NO: 57; SP1872 ABC-transporter protein SEQ ID NO: 58; SP1891 ABC-transporter protein SEQ ID NO: 59; SP2084 ABC-transporter protein SEQ ID NO: 68; SP2197 ABC-transporter protein SEQ ID NO: 74.
Accordingly, Malley et al disclose an immunogenic composition comprising at least 2, 3, etc. proteins from S.pneumoniae or functional fragments/antigenic determinants thereof, which may be ABC-T, PavA and/or ZmpB. Claim 12 ecites that the composition is “delivered by”, but this language does not positively recite that any of these elements are included in the composition. “Delivered by” is an intended use only. The PVVs, VLPs, etc. are not required by the claim. It is unclear if these are to be included in the composition.
Rappouli et al teaches S. pneumoniae zinc metalloprotease ZmpB, SEQ ID 64. 99.7% to Applicants’ SEQ ID NO: 3, Camilli et al WO2004020609-A2. Teaches pneumoniae antigenic protein sequence Seq ID No: 343. 99.4% to Applicants’ SEQ ID NO: 2
Yibing et al and Yi et al disclose ZMP-B or fragments thereof for eliciting immunity against S. pneumoniae infection. The compositions of Yi are administered with Alum or endopeptidase O as adjuvants. The compositions of Yibing et al are administered in combination with Freund’s adjuvant or cholera toxin as adjuvants.
Le Page et al teaches Streptococcus pneumoniae ID-219 protein. 98.8% to Applicants’ SEQ ID NO: 1
Houston et al discloses PAV-A or fragments thereof for eliciting protective immunity against S. pneumoniae infection. Houston teaches composition comprising both PAV-A and PspA . See page 21-22. The compositions of Houston are administered with Alum (alhydrogel) as adjuvant. Other adjuvants such as Freunds complete adjuvant, Freunds incomplete adjuvant, dimethyldioctadecyl- ammonium bromide, Adjuvax, Inject Alum, Monophosphoryl Lipid A, MPL+TDM, Titermax, QS21, CpG sequences, CoVaccine HT, toxins, toxoids, glycoproteins, lipids, glycolipids, bacterial cell walls, subunits (bacterial or viral), carbohydrate moieties (mono-, di-, tri-, tetra-, oligo- and polysaccharide), various liposome formulations or saponins or combinations thereof are cited.
Basavanna, S. ("Screening of streptococcus pneumoniae ABC transporters for their role in virulence and investigation of their lipoprotein components as vaccine candidates", 28 November 201. Nov. 2011; provided by Applicants), Jomma et al (Vaccine. 24(24): 5133-5139. June 2006; provided by Applicants) and Franziska (: "Immunogenicity and protectivity of surface-localized lipoproteins of Streptococcus pneumoniae", 18 December 2018. Pages 1-251; provided by Applicants) disclose that S. pneumoniae ABC-transporters are surface-exposed, are involved in virulence, and that some of them elicit protective immunity when administered to a subject.
In view of these prior art reference, which teach all of the proteins of claim 1 and their use in immunogenic compositions, it would have been prima facie obvious to combine these well-known immunogenic proteins ZMP-B and PAV-A or an ABC-transporter and ZMPB or PAV-A with the reasonable expectation they would be at least as immunoprotective, and likely more so, as the compositions disclosed in the individual documents. One of ordinary skill in the art would be motivated to do so to provide a wider immune response. Therefore, it would have been prima facie obvious to combine any of these proteins, including any derivates or analogs or fragments of these proteins as recited in the instant claims, to provide for an effective immune composition.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 4, 5, 11, 13 and 14 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter because the claims are drawn to isolated proteins which exists in nature. The claimed proteins are not markedly different from what naturally exists in nature. Even though isolation structurally changes a protein from its natural state, the resultant difference is no enough to render the isolated protein markedly different because the genetic structure and sequence of the nucleic acid has not been altered. It is noted that a S. pneumoniae bacteria would naturally comprise a ABC-T, PavA and ZmpB protein and the claims does not recite ‘isolated’ so the whole cell wild-type S. pneumoniae bacteria reads on the claim. A “liquid” in claim 11 reads on water which would not change the composition and would be inherent. See Myriad, 133 S.Ct. at 2166-18.
Response to Applicants arguments:
Applicants argue:
Claim 1, as amended, now recites that an effective amount of each protein is used such that the immunogenic composition elicits an immune response when administered to a mammal. Applicant believes that recitation of this effective amount, as well as inclusion of the specific protein sequences now recited, overcomes the grounds for the § 101 rejection
This has been fully and carefully considered but is not deemed persuasive. The claims still read on a naturally-occurring bacterium. An amino acid sequence is an inherent property of a protein and ‘an effective amount’ does not change the structure of the claimed composition, nor is it defined in the claims. It is also noted that the specification does not provide information about what “an effective amount” would constitute. The claims read on a composition comprising all three naturally-occurring proteins which all are found in the same naturally-occurring bacterium.
Applicants’ amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicants are 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.
Correspondence regarding this application should be directed to Group Art Unit 1645. Papers related to this application may be submitted to Group 1600 by facsimile transmission. Papers should be faxed to Group 1600 via the PTO Fax Center located in Remsen. The faxing of such papers must conform with the notice published in the Official Gazette, 1096 OG 30 (November 15,1989). The Group 1645 Fax number is 571-273-8300 which is able to receive transmissions 24 hours/day, 7 days/week.
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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 7/23/26
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