Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
1. Applicant’s preliminary amendment filed on May 9, 2025 is acknowledged. Claims 1-76, 78-79, 82-85, 87-169, 172-230, and 232-448 have been canceled. Claims 77, 80, 81, 86, 170-171, and 231 have been amended. Claims 449-463 have been added. Claims 77, 80-81, 86, 170-171, 231, and 449-463 are currently pending and under examination.
Information Disclosure Statement
2. The information disclosure statement (IDS) submitted on May 9, 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. An initialed copy is attached hereto.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
3. Claims 77, 80-81, 86, 170-171, 231,and 449-463 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 11 and 20 of U.S. Patent No. 12,257,295. Although the claims at issue are not identical, they are not patentably distinct from each other because the pending claims are drawn to a pharmaceutical composition comprising at least two immunogenic saccharide-polypeptide conjugates, each comprising individually capsular polysaccharide, fragment thereof, or combination thereof conjugated to a polypeptide, wherein each of the capsular polysaccharides, fragments thereof, or combinations thereof is from a Streptococcus pneumoniae serotype selected from 1, 2, 3, 4, 5, 6A, 6B, 6C, 7C, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15A, 15B, 15C, 16F, 17F, 18C, 19A, 19F, 20A, 20B, 22F, 23A, 23B, 23F, 24B, 24F, 31, 33F, 33B, 34, 35B, 35F, and 38.
Meanwhile the patented claims anticipate and/or makes obvious the pending claims. Specifically, claim 1 is drawn to a pharmaceutical composition comprising a plurality of immunogenic saccharide-polypeptide conjugates, each comprising individually a capsular polysaccharide, fragment thereof, or combination thereof conjugated to a polypeptide, wherein each of the capsular polysaccharides, fragments thereof, or combinations thereof is from a Streptococcus pneumoniae serotype; wherein the Streptococcus pneumoniae serotypes in the plurality of immunogenic saccharide-polypeptide conjugates comprise at least serotypes 6C, 8, 9N, 10A, 11A, 12F, 15A, 20B, 22F, 23A, 23B, 24F, 33F, and 35B; and wherein the fragment or fragments of the capsular polysaccharide is a monosaccharide, a disaccharide, a trisaccharide, a tetrasaccharide, a pentasaccharide, a hexasaccharide, or an oligosaccharide.
As it pertains to claims 81 and 86, limitations such as their specific amounts and doses are being viewed as limitations of optimizing experimental parameters.
4. Claims 77 and 170 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 449-451 of U.S. Patent No. 11,058,757. Although the claims at issue are not identical, they are not patentably distinct from each other because the pending claims are drawn to a pharmaceutical composition comprising at least two immunogenic saccharide-polypeptide conjugates, each comprising individually capsular polysaccharide, fragment thereof, or combination thereof conjugated to a polypeptide, wherein each of the capsular polysaccharides, fragments thereof, or combinations thereof is from a Streptococcus pneumoniae serotype selected from 1, 2, 3, 4, 5, 6A, 6B, 6C, 7C, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15A, 15B, 15C, 16F, 17F, 18C, 19A, 19F, 20A, 20B, 22F, 23A, 23B, 23F, 24B, 24F, 31, 33F, 33B, 34, 35B, 35F, and 38.
Meanwhile, the patented claims are drawn to a pharmaceutical composition comprising a plurality of at least two unique immunogenic saccharide-polypeptide conjugates, each comprising individually a capsular polysaccharides conjugated to a polypeptide, wherein each of the capsular polysaccharides is from a Streptococcus pneumoniae serotype selected from a group consisting of 23A, 23B, and 35B. The patented claims anticipates the pending claims.
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.
5. Claim(s) 77, 80-81, 86, 170-171, 231, 449-452, 455-460 and 463 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Caulfield et al., US 8,192,746 B2; Published: 6/5/12.
Independent claim 77 is drawn to a pharmaceutical composition comprising at least two immunogenic saccharide-polypeptide conjugates, each comprising individually capsular polysaccharide, fragment thereof, or combination thereof conjugated to a polypeptide, wherein each of the capsular polysaccharides, fragments thereof, or combinations thereof is from a Streptococcus pneumoniae serotype selected from 1, 2, 3, 4, 5, 6A, 6B, 6C, 7C, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15A, 15B, 15C, 16F, 17F, 18C, 19A, 19F, 20A, 20B, 22F, 23A, 23B, 23F, 24B, 24F, 31, 33F, 33B, 34, 35B, 35F, and 38.
Caulfield discloses a multivalent immunogenic composition comprising, consisting essentially of, or alternatively, consisting of 15 distinct polysaccharide-protein conjugates, wherein each of the conjugates contains a different capsular polysaccharide conjugated to a carrier protein, and wherein the capsular polysaccharides are prepared from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F of S. pneumoniae, together with a pharmaceutically acceptable carrier. In certain embodiments, the carrier protein is CRM197 (see column 2, lines 65-67 and column 3, lines 1-7; meeting claims 77, 170, 449-451, 455).
Applicants' finding that a 15 valent pneumococcal conjugate vaccine including the addition of new polysaccharide-protein conjugates containing serotypes 22F and 33F provides robust antibody responses demonstrates the feasibility of expanding coverage of pneumococcal serotypes not covered by existing pneumococcal vaccines (see column 3, lines 20-25; meeting claims 80 and 171). Carrier proteins are preferably proteins that are non-toxic and non-reactogenic and obtainable in sufficient amount and purity. A carrier protein can be conjugated or joined with a S. pneumoniae polysaccharide to enhance immunogenicity of the polysaccharide.
Coupling to the protein carrier (e.g., CRM197) can be by reductive amination via direct amination to the lysyl groups of the protein. For example, conjugation is carried out by reacting a mixture of the activated polysaccharide and carrier protein with a reducing agent such as sodium cyanoborohydride. In another embodiment, the conjugation method may rely on activation of the saccharide with 1-cyano-4-dimethylamino pyridinium tetrafluoroborate (CDAP) to form a cyanate ester. The activated saccharide may thus be coupled directly or via a spacer (linker) group to an amino group on the carrier protein. For example, the spacer could be cysteamine or cysteamine to give a thiolated polysaccharide which could be coupled to the carrier via a thioether linkage obtained after reaction with a maleimide-activated carrier protein (for example using GMBS) or a haloacetylated carrier protein (for example using iodoacetamide [e.g. ethyl iodoacetamide HCl] or N-succinimidyl bromoacetate or SIAB, or SIA, or SBAP). Preferably, the cyanate ester (optionally made by CDAP chemistry) is coupled with hexane diamine or adipic acid dihydrazide (ADH) and the amino-derivatized saccharide is conjugated to the carrier protein using carbodiimide (e.g. EDAC or EDC) chemistry via a carboxyl group on the protein carrier (see column 5, lines 18-42; ; Example 2; meets claims 452, 457-560).
Moreover, in one embodiment, prior to formulation, each pneumococcal capsular polysaccharide antigen is individually purified from S. pneumoniae, activated to form reactive aldehydes, and then covalently conjugated using reductive amination to the carrier protein CRM197 (see column 5, claims 61-65; meets claim 77). The present invention further provides compositions, including pharmaceutical, immunogenic and vaccine compositions, comprising, consisting essentially of, or alternatively, consisting of 15 distinct polysaccharide-protein conjugates, wherein each of the conjugates contains a different capsular polysaccharide conjugated to a carrier protein, and wherein the capsular polysaccharides are prepared from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F of S. pneumoniae, together with a pharmaceutically acceptable carrier and an adjuvant (see column 6, lines 8-17; meets claims 456 and 463).
Further, administration of the compositions of the invention can include one or more of: injection via the intramuscular, intraperitoneal, intradermal or subcutaneous routes; or via mucosal administration to the oral/alimentary, respiratory or genitourinary tracts. In one embodiment, intranasal administration is used (see column 8, lines 42-46; meets claim 231). The amount of conjugate in each vaccine dose is selected as an amount that induces an immunoprotective response without significant, adverse effects. Such amount can vary depending upon the pneumococcal serotype. Generally, each dose will comprise 0.1 to 100 μg of each polysaccharide, particularly 0.1 to 10 μg, and more particularly 1 to 5 μg (see column 8, lines 51-56; meets claims 81 and 86). Absent evidence to the contrary, the serotype in the composition encompasses from about 0% to about 30% w/w.
Since the Office does not have the facilities for examining and comparing applicants’ composition with the composition of the prior art, the burden is on applicant to show a novel or unobvious difference between the claimed product and the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
6. Claim(s) 77, 81, 86, 170-171, 231, 449, and 455-456 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Prasad, US 8,603,424 B2; Published: 12/10/13.
Independent claim 77 is drawn to a pharmaceutical composition comprising at least two immunogenic saccharide-polypeptide conjugates, each comprising individually capsular polysaccharide, fragment thereof, or combination thereof conjugated to a polypeptide, wherein each of the capsular polysaccharides, fragments thereof, or combinations thereof is from a Streptococcus pneumoniae serotype selected from 1, 2, 3, 4, 5, 6A, 6B, 6C, 7C, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15A, 15B, 15C, 16F, 17F, 18C, 19A, 19F, 20A, 20B, 22F, 23A, 23B, 23F, 24B, 24F, 31, 33F, 33B, 34, 35B, 35F, and 38.
Prasad discloses an immunogenic composition having 13 distinct polysaccharide-protein conjugates and optionally, an aluminum-based adjuvant, is described. Each conjugate contains a capsular polysaccharide prepared from a different serotype of Streptococcus pneumoniae (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) conjugated to a carrier protein. The immunogenic composition, formulated as a vaccine, increases coverage against pneumococcal disease in infants and young children globally, and provides coverage for serotypes 6A and 19A that is not dependent on the limitations of serogroup cross-protection (see abstract; meets claims 77, 170-171, 455 and 456).
Carrier proteins are preferably proteins that are non-toxic and non-reactogenic and obtainable in sufficient amount and purity. Carrier proteins should be amenable to standard conjugation procedures. In a particular embodiment of the present invention, CRM197 is used as the carrier protein. CRM197 (Wyeth, Sanford, N.C.) is a non-toxic variant (i.e., toxoid) of diphtheria toxin isolated from cultures of Corynebacterium diphtheria strain C7 (β197) grown in casamino acids and yeast extract-based medium. CRM197 is purified through ultra-filtration, ammonium sulfate precipitation, and ion-exchange chromatography. Other diphtheria toxoids are also suitable for use as carrier proteins. Other suitable carrier proteins include inactivated bacterial toxins such as tetanus toxoid, pertussis toxoid, cholera toxoid, E. coli LT, E. coli ST, and exotoxin A from Pseudomonas aeruginosa. Bacterial outer membrane proteins such as outer membrane complex c (OMPC), porins, transferrin binding proteins, pneumolysin, pneumococcal surface protein A (PspA), pneumococcal adhesin protein (PsaA), C5a peptidase from Group A or Group B streptococcus, or Haemophilus influenzae protein D, can also be used. Other proteins, such as ovalbumin, keyhole limpet hemocyanin (KLH), bovine serum albumin (BSA) or purified protein derivative of tuberculin (PPD) can also be used as carrier proteins (see column 9, lines 1-29; meets claim 449).
Moreover, the vaccine formulations of the present invention can be used to protect or treat a human susceptible to pneumococcal infection, by means of administering the vaccine via a systemic or mucosal route. These administrations can include injection via the intramuscular, intraperitoneal, intradermal or subcutaneous routes; or via mucosal administration to the oral/alimentary, respiratory or genitourinary tracts. In one embodiment, intranasal administration is used (see column 10, lines 53-60; meets claim 231).
The amount of conjugate in each vaccine dose is selected as an amount that induces an immunoprotective response without significant, adverse effects. Such amount can vary depending upon the pneumococcal serotype. Generally, each dose will comprise 0.1 to 100 μg of polysaccharide, particularly 0.1 to 10 μg, and more particularly 1 to 5 μg (see column 11, lines 8-12; meets claim 81 and 86). Absent evidence to the contrary, the serotype in the composition encompasses from about 0% to about 30% w/w.
Since the Office does not have the facilities for examining and comparing applicants’ composition with the composition of the prior art, the burden is on applicant to show a novel or unobvious difference between the claimed product and the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Conclusion
7. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Biemans WO 2009/000826; Hausdorff US 8,808,708 B2.
8. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAKIA J JACKSON-TONGUE whose telephone number is (571)272-2921. The examiner can normally be reached Monday-Friday 930AM-530PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at (571) 272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LAKIA J JACKSON-TONGUE/Examiner, Art Unit 1645 August 8, 2026
/BRIAN GANGLE/Primary Examiner, Art Unit 1645
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