DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/26/2026 has been entered.
Disposition of Claims
Claims 1, 3-14, 17-19, 21-23, 25-26, and 28 were pending. Claims 2, 9, 15-16, 20, 24, and 27 are cancelled. Amendments to claim 1, 11, 13, and 22 are acknowledged and entered. Claims 1, 3-8, 10-14, 17-19, 21-23, 25-26, and 28 will be examined on their merits.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US20220031829A1, Published 02/03/2022.
The Power of Attorney filed on 02/28/2024 is acknowledged and entered.
Response to Arguments
Applicant's arguments filed 05/22/2026 regarding the previous Office action dated 02/26/2026 have been fully considered. If they have been found to be persuasive, the objection/rejection has been withdrawn below. Likewise, if a rejection/objection has not been recited, said rejection/objection has been withdrawn. If the arguments have not been found to be persuasive, or if there are arguments presented over art that has been utilized in withdrawn rejections but utilized in new rejections, the arguments will be addressed fully with the objection/rejection below.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim 1 is drawn to a method of immunization against Neisseria meningitidis serogroups A, C, Y, and W-135 and human papilloma virus (HPV) without interference with the development of immunity against one or more types of HPV including HPV types 6 and 18, the method comprising:
co-administering a Neisseria meningitidis vaccine composition, an HPV Type 6 L1 protein, an HPV Type 11 L1 protein, an HPV Type 16 L1 protein, and an HPV Type 18 L1 protein to a subject in need thereof, wherein the HPV Type 6 L1 protein, the HPV Type 11 L1 protein, the HPV Type 16 L1 protein, and the HPV Type 18 L1 protein are each in the form of virus-like particles (VLPs), and
the Neisseria meningitidis vaccine composition comprises:
a) a first conjugate of MenA capsular polysaccharide to tetanus toxoid, wherein the MenA capsular polysaccharide is attached to the tetanus toxoid through a linker comprising a carbamate, a spacer, and an amide, wherein the spacer is between the carbamate and the amide and comprises 2-10 linear carbons, and the first conjugate has a polysaccharide to tetanus toxoid mass ratio of 0.3 to 1.5;
b) a second conjugate of MenC capsular polysaccharide to tetanus toxoid, wherein the second conjugate is a population comprising double-end-linked conjugated polysaccharides and single-end-linked conjugated polysaccharides which both are attached to the tetanus toxoid through a secondary amine, and/or the polysaccharides of the second conjugate have an O-acetylation level of 0.3 mol/mg polysaccharide to 1.6 mol/mg polysaccharide;
c) a third conjugate of MenW-135 capsular polysaccharide to tetanus toxoid;
d) a fourth conjugate of MenY capsular polysaccharide to tetanus toxoid;
e) the MenC, MenW-135, and MenY capsular polysaccharides are directly attached to the tetanus toxoid through a secondary amine and at least one of the conjugates has a weight average molecular weight ranging from 300 kDa to 1500 kDa; and
f) less than 20% free polysaccharide by weight;
and wherein the administration of the Neisseria meningitidis vaccine composition does not interfere with the development of immunity against HPV Types 6 and 18,
wherein the Neisseria meningitidis vaccine composition is administered as a first vaccine and a vaccine composition comprising the HPV Type 6 L1 protein, the HPV Type 11 L1 protein, the HPV Type 16 L1 protein, and the HPV Type 18 L1 protein is administered as a second vaccine;
wherein "does not interfere" means that coadministration of the first vaccine with the second vaccine to a treatment group gives a titer specific for an antigen of the second vaccine where the lower bound of its 95% confidence interval is greater than two thirds of the titer of a control group given only the second vaccine and that coadministration of the first vaccine with the second vaccine to a treatment group gives an amount of seroconversion against an antigen of the second vaccine where the lower bound of its 95% confidence interval is greater than 90% of the seroconversion of a control group given only the second vaccine.
Further limitations on the method according to claim 1 are wherein administration of the Neisseria meningitidis vaccine composition does not interfere with the development of immunity against (i) HPV Types 6, 11, and 18 or (ii) HPV types 6, 16, and 18 (claim 3); wherein the administration of the Neisseria meningitidis vaccine composition does not interfere with the development of immunity against HPV types 11 and 16 (claim 4); wherein the administration of the HPV types 6 and 18 L1 proteins does not interfere with the development of immunity against Neisseria meningitidis serogroups A, C, Y, and/or W-135 (claim 5); wherein interference or non- interference with the development of immunity against HPV Type 18 is determined by comparing (i) the geometric mean antibody titer specific for HPV Type 18 L1 protein in a first treatment group treated with the Neisseria meningitidis vaccine composition and co-administered with the HPV Type 18 L1 protein with (ii) the geometric mean antibody titer specific for HPV Type 18 L1 protein in a second treatment group treated with the HPV Type 18 L1 protein without the Neisseria meningitidis vaccine composition (claim 6); wherein the coadministration of the Neisseria meningitidis vaccine composition and the HPV protein does not result in increased risk of injection site swelling relative to administration of the HPV type 18 L1 protein without the Neisseria meningitidis vaccine composition (claim 7); further comprising co-administering a diphtheria-tetanus-pertussis vaccine with the Neisseria meningitidis vaccine composition (claim 8), wherein the diphtheria-tetanus- pertussis vaccine is Tetanus, diphtheria, acellular pertussis (Tdap) vaccine or DTaP5, optionally wherein the administration of the diphtheria-tetanus-pertussis vaccine does not interfere with the development of immunity against Neisseria meningitidis serogroups A, C, Y, and/or W-135 (claim 18); wherein the first, second, third, and/or fourth conjugates are a population comprising molecules with a molecular weight in the range of 700 kDa to 1400 kDa or 800 kDa to 1300 kDa, optionally wherein molecular weight is determined by multi-angle light scattering (MALS)(claim 10), wherein the first, second, third, and/or fourth conjugates are a population comprising molecules with a molecular weight in the range of 800 kDa to 1300 kDa (claim 23); wherein: (i) the MenC polysaccharide has a degree of O-acetylation ranging from 0.6 to 1.5 mol/mg polysaccharide or 0.8 to 1.4 mol/mg polysaccharide; (ii) the conjugate comprising MenC polysaccharide is a population comprising double- end-linked conjugated polysaccharides and single-end-linked conjugated polysaccharides, optionally wherein the single-end-linked polysaccharides of the second conjugate comprise a terminal unlinked saccharide, wherein the single-end-linked conjugated polysaccharides have a terminal unlinked saccharide, wherein the terminal saccharide has a primary hydroxyl at the 7 position, or wherein the reducing end is modified with a (2- hydroxy) ethoxy; (iii) the conjugate comprising MenC polysaccharide comprises one or more modifications chosen from (a) a primary hydroxyl at the 7 position, (b) a (2-hydroxy)ethoxy at the reducing end, and (c) a conjugation to the tetanus toxoid, wherein the modifications are present at no less than 25 nmol/mg polysaccharide; (iv) the conjugate of MenW-135 and/or MenY polysaccharide comprises one or more modifications chosen from (a) a primary hydroxyl at a position of a vicinal diol in a native MenW-135 or MenY polysaccharide and (b) a conjugation to the tetanus toxoid, wherein the modifications are present at no less than 60 nmol/mg polysaccharide; (v) the MenC polysaccharide is reduced in size by 3x-8x relative to native MenC polysaccharide; and/or (vi) the Neisseria meningitidis vaccine composition comprises less than 10% free polysaccharide by weight (claim 11); wherein: (i) the conjugate of the MenA capsular polysaccharide to the tetanus toxoid has a polysaccharide to tetanus toxoid mass ratio of 0.5 to 1.5 (ii) the conjugate of the MenC capsular polysaccharide to the tetanus toxoid has a polysaccharide to tetanus toxoid mass ratio of 0.3 to 1.1(iii) the conjugate of the MenY capsular polysaccharide to the tetanus toxoid has a polysaccharide to tetanus toxoid mass ratio of 0.3 to 1.1; and/or (iv) the conjugate of MenW-135 capsular polysaccharide to the tetanus toxoid has a polysaccharide to tetanus toxoid mass ratio of 0.3 to 1.3 (claim 12), wherein: (i) the conjugate of the MenA capsular polysaccharide to the tetanus toxoid has a polysaccharide to tetanus toxoid mass ratio of 0.7 to 1.4; (ii) the conjugate of the MenC capsular polysaccharide to the tetanus toxoid has a polysaccharide to tetanus toxoid mass ratio of 0.4 to 0.8; (iii) the conjugate of the MenY capsular polysaccharide to the tetanus toxoid has a polysaccharide to tetanus toxoid mass ratio of 0.5 to 1.1; and/or (iv) the conjugate of MenW-135 capsular polysaccharide to the tetanus toxoid has a polysaccharide to tetanus toxoid mass ratio of 0.6 to 1.3 (claim 22); wherein the linker in the MenA conjugate: (i) is present at a ratio of one linker per 10-100 saccharide repeat units or 20-60 saccharide repeat units; and/or (ii) comprises the spacer between a first carbonyl and a second carbonyl, and the spacer comprises 4-8 carbons (claim 13); wherein: (i) the MenA conjugate comprises a linker comprising a residue of a dihydrazide or a residue of adipic acid dihydrazide, optionally wherein the polysaccharide of the MenA capsular polysaccharide of the first conjugate is attached to the tetanus toxoid through a linker of formula I:
PNG
media_image1.png
158
454
media_image1.png
Greyscale
wherein PS indicates attachment to the polysaccharide and PR indicates attachment to the tetanus toxoid; and/or (ii) the polysaccharide of the MenC, MenW-135, and/or MenY conjugate is attached to the tetanus toxoid as shown in formula II: PR-NH-CH2-PS (II) wherein PS indicates attachment to the polysaccharide and PR indicates attachment to the tetanus toxoid (claim 14);
wherein (i) the HPV Type 6 L1 protein is present in a dose of 20 ug;
(ii) the HPV Type 11 L1 protein is present in a dose of 40 ug;
(iii) the HPV Type 16 L1 protein is present in a dose of 40 ug; and/or
(iv) the HPV Type 18 L1 protein is present in a dose of 20 ug (claim 17); wherein the HPV vaccine comprises one, two, three, four, or all of:(i) amorphous aluminum hydroxyphosphate sulfate adjuvant;(ii) sodium chloride;(iii) L-histidine;(iv) polysorbate 80; and/or (v) sodium borate (claim 19), wherein the HPV types in the HPV vaccine consist of HPV types 6, 11, 16, and 18 (claim 21); wherein interference or non-interference with the development of immunity against HPV Type 6 is determined by comparing (i) the geometric mean antibody titer specific for HPV Type 6 L1 protein in a first treatment group treated with the Neisseria meningitidis vaccine composition and co-administered with the HPV Type 6 L1 protein with (ii) the geometric mean antibody titer specific for HPV Type 6 L1 protein in a second treatment group treated with the HPV Type 6 L1 protein without the Neisseria meningitidis vaccine composition (claim 25); wherein the coadministration of the Neisseria meningitidis vaccine composition and the HPV Type 6 L1 protein does not result in increased risk of injection site swelling relative to administration of the HPV Type 6 L1 protein without the Neisseria meningitidis vaccine composition (claim 26); and wherein the administration of the HPV Type 11L1 protein and the HPV Type 16 L1 protein does not interfere with the development of immunity against Neisseria meningitidis serogroups A, C, Y, and/or W-135 (claim 28).
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection withdrawn.) The rejection of Claims 1, 3-14, 17-19, 21-23, 25-26, and 28 under 35 U.S.C. 103 as being unpatentable over Bigio et. al. (US20100239600A1, Pub. 09/23/2010; CITED ART OF RECORD; hereafter “Bigio”) and further in view of
Anderson et. al. (WO2016132294A1, Pub. 08/25/2016; CITED ART OF RECORD; hereafter “Anderson”), and
Sanofi Pasteur (Sanofi Pasteur. “Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Healthy Adolescents.” ClinicalTrials.gov ID NCT02199691; V1, 07/23/2014; hereafter “Sanofi Pasteur”);
as evidenced by Merck & Co., Inc. (Merck & Co., Inc. GARDASIL® Package Insert. 2011, p. 1-28.; CITED ART OF RECORD; hereafter “Merck”);
Rivera et. al. (Rivera L, et. al. Vaccine. 2018 Jun 22;36(27):3967-3975. Epub 2018 May 19.; CITED ART OF RECORD; hereafter “Rivera”);
Shafer et. al. (Shafer DE, et. al. Vaccine. 2001 Jan 8;19(11-12):1547-58.; hereafter “Shafer”);
Simon et. al. (WO2012061400A2, Pub. 05/10/2012, hereafter “Simon”);and
Arguedas et. al. (Arguedas A, et. al. Vaccine. 2010 Apr 19;28(18):3171-9. Epub 2010 Feb 26.; CITED ART OF RECORD; hereafter “Arguedas”) is withdrawn in light of the amendments to the claims.
Double Patenting
The text regarding nonstatutory double patenting (NSDP) was presented in a previous Office action.
(Rejection maintained in part and extended – necessitated by amendment.) Claims 1, 3-8, 10-14, 17-19, 21-23, 25-26, and 28 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 11,147,866 in view of Sanofi Pasteur, Bigio, Anderson, Rivera, and Arguedas (supra). Note the rejection of claim 9 is withdrawn in light of the cancellation of said claim.
The rationale behind this rejection was set forth in a previous Office action and will not be repeated herein.
(Rejection maintained in part and extended – necessitated by amendment.) Claims 1, 3-8, 10-14, 17-19, 21-23, 25-26, and 28 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 11,707,514 in view of Bigio, Sanofi Pasteur, Anderson, Rivera, and Arguedas (supra). Note the rejection of claim 9 is withdrawn in light of the cancellation of said claim.
The rationale behind this rejection was set forth in a previous Office action and will not be repeated herein.
Response to Arguments
Applicant's arguments filed 05/22/2026 have been fully considered and are not persuasive.
Applicant argues with respect to the rejections over the ‘514 and ‘866 patent claims that the patented claims in view of the secondary references could not have been modified to reach the recited non-interference limitation, and that it could not have been predicted that the specific MenACWY-TT vaccine composition administered with the quadrivalent HPV vaccine composition would not interfere with the HPV immune response. This argument is not persuasive.
The nonstatutory double patenting rejection does not require modification of the patented MenACWY-TT composition to create a new structure having a newly disclosed property. Rather, the patented claims already recite a MenACWY-TT vaccine composition which comprises the same conjugation chemistry as the instant claims were amended to comprise. The pending claims add administration of a known quadrivalent HPV vaccine composition (e.g. Merck’s teachings with GARDASIL®) as a separate vaccine composition, and recite maintenance of the HPV immune response, including the HPV types 6 and 18 immune responses, as measured by titer and seroconversion endpoints.
The secondary references (Bigio, Sanofi Pasteur, Anderson, Rivera, and Arguedas) are relied upon to show that this added feature would have been an obvious variation of the patented claims. The art taught quadrivalent HPV vaccine compositions comprising VLPs comprised of L1 proteins from HPV 6, 11, 16, and 18. The art further taught concomitant administration of HPV vaccines with meningococcal conjugate vaccines and reported that such coadministration did not materially interfere with immune responses. Rivera further taught coadministration of MenACWY-TT with an HPV vaccine and reported non-inferior immunogenicity upon coadministration. Anderson, Arguedas, and Rivera further provide evidence that antibody titer, geometric mean titer, seroconversion, seroresponse, and non-inferiority comparisons were conventional endpoints for determining whether vaccine co-administration resulted in immunological interference.
Applicant’s arguments improperly requires certainty of success. Obviousness does not require that the prior art have tested the identical vaccine pair later claimed, nor does it require absolute certainty/predictability of the exact clinical result. The proper inquiry is whether one of ordinary skill in the art would have a reason to administer these two vaccines together (e.g. MenACWY-TT and quadrivalent HPV) with a reasonable expectation of success that the HPV immune response would be maintained. Here, the art provided such a reason and reasonable expectation, because HPV vaccines and meningococcal vaccines were known adolescent vaccines suitable for concomitant administration, and clinical studies had already shown maintained immune responses upon co-administration of HPV vaccines with meningococcal conjugate vaccines, including studies using titer based and seroconversion/seroresponse based immune endpoints.
Accordingly, the claimed “does not interfere” limitation reflects the reasonably expected result of administering known vaccine compositions according to known co-administration practices and evaluating the immune response using conventional non-interference endpoints.
For at least these reasons, the instant claims are not patentably distinct from the ‘514 and ‘866 patented claims in view of the prior art.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Reisinger et. al. (Reisinger KS, et. al. Pediatrics. 2010 Jun;125(6):1142-51. Epub 2010 May 3.; Teaches concomitant administration of MenACWY-CRM with HPV and dTap vaccines. Utilizes different carrier from the MenACWY vaccine of the instant claims.
.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL B GILL whose telephone number is (571)272-3129. The examiner can normally be reached on M to F 8:00 AM to 5:00 PM Eastern.
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, Michael Allen can be reached on (571) 270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/RACHEL B GILL/Primary Examiner, Art Unit 1671
Prosecution Insights