DETAILED ACTION
Election/Restrictions
Applicant's election with traverse of Group I, claims 1, 4-14; for claim 10- Applicant elects the Species ABC transporter (PsaA), in the reply filed on 11/7/25 is acknowledged. The traversal is on the ground(s) that:
Applicants argue that there is a link by common inventive concept because the identification of a particular group of antigens that are particularly effective when used in combinations of a least two of the antigens. Applicant respectfully believes that multi-antigen outcomes are unpredictable, both clinical and preclinical studies have shown that protection is not guaranteed, and certainly that improved performance cannot be predicted with any degree of certainty. In particular, the outcome of combining multiple protein antigens in a single immunogenic composition cannot be predicted from single-antigen data due to several well-recognized immunological phenomena, including antigenic competition and immune interference (i.e., the response to one antigen may be reduced by the presence of others, owing to competition for antigen presentation pathways, carrier-induced suppression, or bystander interference), and immunodominance and epitope masking (the immune system often focuses on dominant epitopes; adding antigens can shift response hierarchies or suppress cellular immunity). In contrast, Applicant's specification presents clear evidence of the improved immunoprotection provided by combining pairs or all three of the specified antigens.
This has been fully and carefully considered but is not found persuasive because the antigens were known in the prior art and the combination does not provide an unexpected result. The claims also include ‘antigenic determinants’, e.g., not necessarily full-length proteins. There is no evidence that these different combinations would suffer from “epitope masking.” In view of these cited prior art references, which teach all of the proteins of claim 1, 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 in order to provide a wider immune response. See also newly presented prior art cited below, Malley et al (WO 2104/124228), which teaches at least two or three of the claimed proteins/epitopes in a single composition.
The requirement is still deemed proper and is therefore made FINAL.
Claims 2, 3 and 15-21 are withdrawn from consideration for being drawn to a non-elected invention. Claims 15-17 and 21 were in Group III, methods, in the response mailed on 9/8/25. Their inclusion in Group I was a typographical error. Group II, comprised claims 2, 3-14, 19 and 20 due to the multi-dependency issue of claims 4-14, 19 and 20 making them unclear (nucleic acid; claim 2 is independent so the nucleic acid claims when multi-dependency is corrected will be in Group II).
Claims 1, and 4-14 (proteins) of Group I are currently under examination.
Claim 1 is currently under examination on the merits.
Claim Objections
Claims 4-14 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from another multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claims 4-14 have not been further treated on the merits.
Note regarding claim 10: Claim 10 will be 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 laundry list of additional antigenic determinants in many different combinations in claim 10 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: they would be expected to have vastly different immunogenic profiles.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112-2nd 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 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is vague and indefinite because it is unclear what structures are encompassed by antigenic determinants “derived from” ABC-T, PavA and ZmpB or Streptococcus pneumoniae bacterium. The term "antigenic determinant" is vague the term "derived" from does not place any limitation as to the amino acid sequence since the type and extent of the derivation are not mentioned in the claim. The term “derived/derivative” does not provide the character or properties from the source that are to be retained in the final product, e.g., paper is derived from wood but is very different from wood. Additionally, the use of names alone to describe ABC-T, PAV-A and Zmp-B are not fully clear in the absence of a reference to specific amino acid sequences. This is in particular true for ABC-T since this term, which may designate an ABC transporter protein, covers a myriad of S. pneumoniae proteins. ABC transporter proteins have different properties and biological properties. See Voss Franziska (: "Immunogenicity and protectivity of surface-localized lipoproteins of Streptococcus pneumoniae", 18 December 2018. Pages 1-251; table 3.1 provided by Applicants), table 3.1, and also 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). ABC transporter proteins have different properties and biological properties. Accordingly, the mere recitation of a name, e.g., ABC-T, to describe the invention is not sufficient to satisfy the Statute's requirement of adequately describing and setting forth the inventive concept. The claim should provide any structural properties, such as the amino acid sequence of the protein or epitope, which would allow for one to identify the protein/epitope without ambiguity. Appropriate clarification and/or correction is required.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Malley et al (WO 2014/124228; published 8/14/2014- 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 elicits 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, in particular 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, since 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, it anticipates claim 1.
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.
Claim 1 is 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. See Myriad, 133 S.Ct. at 2166-18.
Pertinent prior art, not presently relied upon:
Rappouli et al WO2011030218-A1. S. pneumoniae zinc metalloprotease ZmpB, SEQ ID 64. 99.7% to Applicants’ SEQ ID NO: 3.
Camilli et al WO2004020609-A2. S pneumoniae antigenic protein sequence SeqID343. 99.4% to Applicants’ SEQ ID NO: 2.
Le Page et al WO200279241-A2. Streptococcus pneumoniae ID-219 protein. 98.8% to Applicants’ SEQ ID NO: 1.
Yibing et al (CN 109456393; provided by Applicants) and Yi etal (Infect. Immun. 79(2): 867-868. Feb. 2011; provided by Applicants 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.
Houston et al (WO 2005/113602; provided by Applicants) 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, 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 in order to provide a wider immune response. Therefore, Applicant’s invention does not contribute a special technical feature when viewed over the prior art. Additionally, the Inventions in Groups I-III comprise biologically, structurally and chemically distinct products.
Correspondence regarding this application should be directed to Group Art Unit 1645. Papers related to this application may be submitted to Group 1600 by facsimile transmission. Papers should be faxed to Group 1600 via the PTO Fax Center located in Remsen. The faxing of such papers must conform with the notice published in the Official Gazette, 1096 OG 30 (November 15,1989). The Group 1645 Fax number is 571-273-8300 which is able to receive transmissions 24 hours/day, 7 days/week.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jennifer E. Graser whose telephone number is (571) 272-0858. The examiner can normally be reached on Monday-Friday from 8:00 AM-4 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Daniel E. Kolker, can be reached on (571) 272-3181.
Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-0500.
/JENNIFER E GRASER/Primary Examiner, Art Unit 1645 1/30/26