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 .
Claim Status
Claims 2 and 14-16 were canceled.
Claims 1, 3-13 and 17-20 are pending and under consideration.
Withdrawn Rejections
Rejection of Claims 1-13 and 17-20 under 35 U.S.C. 103 as being unpatentable over Blais et al (WO2015/125118) in view of Blue et al (WO 2012/078482) is withdrawn in favor of below rejection.
Provisional rejection of Claims 1-2, 7-11 and 17 on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 and 18-24 of copending Application No. 17/632,299 is withdrawn because Application No. 17/632,299 is now abandoned.
NEW - Claim Rejections - 35 USC § 103
(necessitated by amendments)
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 3-13 and 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Blais et al (WO2015/125118) in view of Blue et al (WO 2012/078482; 11/20/2024 IDS) and Hendericks et al (WO2010/142685; PTO-892).
Regarding claims 1 and 10-11, Blais teaches “The present invention provides a process for preparing an immunogenic composition comprising combining a protein of formula (I) or a protein of the invention with an adjuvant”. Blais teaches an immunogenic composition comprising UspA2 (claim 1 and 18). Blais teaches an immunogenic composition further comprising protein D (claim 23-24). Blais teaches an immunogenic composition further comprising PE-PilA fusion protein (claim 25-27). Therefore, Blais teaches immunogenic composition comprising Protein D, PE-PilA and UspA2. Blais teaches that protein D is from H. influenzae [100]. As evidenced by instant sequence listing and page 40 of instant specification, instant SEQ ID NO: 1 is amino acid sequence for protein D from H. influenzae. Therefore, Blais teaches same protein D from same H. influenzae. Instant SEQ ID NO: 2 is protein D fragment with MDP tripeptide. Therefore, Protein D taught by Blais has at least 90% identity to instant SEQ ID NO: 2 as recited by instant claim 1.
The difference between prior art and the instant invention is that Blais does not teach a composition comprising sucrose and poloxamer.
Regarding claims 1, 3-6, 12, and 17-20, Blue teaches “The present invention provides novel formulations which mitigate agitation-induced aggregation of immunogenic compositions” (corresponds to limitation “reduces the formation of Protein D polypeptide visible particles” of claim 12). Blue teaches “Vaccine formulations must generally be stable and be of uniform consistency to accommodate the need for a long shelf life and the use of multiple dose containers. Vaccines based on proteins, including polysaccharide-protein conjugates, are subject to protein aggregation and precipitation which can result in an effective lower total concentration of the vaccine due to the unavailability of the precipitated protein product. Polysaccharide-protein conjugate vaccines, in particular, appear to have a stronger tendency to aggregate than the carrier protein alone. The choice of formulation for a polysaccharide-protein conjugate vaccine can greatly affect protein aggregation”. Blue teaches “However, the surfactant poloxamer 188 was able to prevent agitation-induced aggregation individually and in combination with the osmolyte sucrose regardless of pH”. Blue teaches a composition comprising 0.1% (w v) Poloxamer 188, 6% (w/v) Sucrose and 50mM NaCl Formulation in a buffer at pH 7.0. Blue teaches “In certain embodiments, the pH buffered saline solution of the formulations of the invention comprises a buffer having a pH of 5.2 to 8.0, 5.2 to 7.5, or 5.8 to 7.0. In certain embodiments, the buffer is phosphate, succinate, histidine, acetate, citrate, MES, MOPS, TRIS or HEPES.” Blue teaches “In certain embodiments, the protein of the polysaccharide-protein conjugate formulation is selected from the group consisting of CRM197, a tetanus toxoid, a cholera toxoid, a pertussis toxoid, an E. coli heat labile toxoid (LT), a pneumolysin toxoid, pneumococcal surface protein A (PspA), pneumococcal adhesin protein A (PsaA), a C5a peptidase from Streptococcus, Haemophilus influenzae protein D, ovalbumin, keyhole limpet haemocyanin (KLH), bovine serum albumin (BSA) and purified protein derivative of tuberculin (PPD).” Therefore, Blue teaches that sucrose and poloxamer can be used to reduce aggregation in composition comprising H. influenzae protein D.
Regarding claims 7-9, thawing protein and mixing with excipients is obvious to one of ordinary skill in the art because protein solutions are usually flash frozen in liquid nitrogen and stored at -70 degree C and this thawing process before use is conventionally performed and well-known routine experimentation in the art. Likewise, filtration composition comprising protein to remove particulates and storing the mixed composition is also conventional laboratory routine experimentation.
Regarding claim 13, Blue teaches “As defined herein, a "polysaccharide-protein conjugate", a "pneumococcal conjugate", a "7-valent pneumococcal conjugate (7vPnC)", "13-valent pneumococcal conjugate (13 vPnC)", and " 15-valent pneumococcal conjugate (15 vPnC)" includes liquid formulations, frozen liquid formulations and solid (e.g., freeze-dried or lyophilized) formulations.” Furthermore, storing formulation as freeze-dried or lyophilized formulation is conventionally performed and well-known routine experimentation in the art.
Regarding newly added limitation “wherein the process comprises mixing the Protein D polypeptide with sucrose and poloxamer prior to mixing the Protein D polypeptide with other antigens”, there would be two possible options of mixing components; i.e. (i) mixing the Protein D polypeptide with sucrose and poloxamer prior to mixing the Protein D polypeptide with other antigens; and (ii) mixing the Protein D polypeptide with sucrose and poloxamer after mixing the Protein D polypeptide with other antigens. One of ordinary skill in the art would reasonably recognize the order of mixing components as “result-effective variable” and envision “a finite number of identified predictable solutions” (i.e. the two options discussed above). Therefore, it would have been obvious to one of ordinary skill in the art to try the finite number of identified predictable solutions through routine experimentation.
Regarding newly added limitation “wherein Protein D is not conjugated to a polysaccharide”, as discussed above, Blue teaches “Vaccines based on proteins, including polysaccharide-protein conjugates, are subject to protein aggregation and precipitation which can result in an effective lower total concentration of the vaccine due to the unavailability of the precipitated protein product”. Therefore, teaching of Blue is not limited to polysaccharide-protein conjugate.
In addition, Henderickx teaches adjuvant compositions comprising a TLR-4 agonist (claim 1). Henderickx teaches “The resulting lyophilisation cake was reconstituted with 625μl of aqueous adjuvant composition and the final composition comprised 4mM Tris, 4mM borate, 4% sucrose, 0.24% Poloxamer 188, 840μg/ml CpG and 1000 μg/ml PRAME”. Therefore, Henderickx teaches that combination of sucrose and poloxamer can be used for generic immunogenic composition which is not limited to polysaccharide-protein conjugate.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added sucrose and poloxamer to the immunogenic composition comprising Protein D, PE-PilA and UspA2 of Blais because Blue and Henderickx teach that sucrose and poloxamer can be used to reduce aggregation in composition comprising H. influenzae protein D. One of ordinary skill in the art would be motivated to test sucrose and poloxamer taught by Blue and Henderickx in the composition of Blais to see whether sucrose and poloxamer can reduce aggregation for the better efficacy of the immunogenic composition.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success because Blue and Henderickx teach that sucrose and poloxamer can be used to reduce aggregation in composition comprising H. influenzae protein D. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHEOM-GIL CHEONG whose telephone number is (571)272-6251. The examiner can normally be reached Monday - Friday 9:00 am - 5:00 pm.
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, Vanessa Ford can be reached at 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CHEOM-GIL CHEONG/Examiner, Art Unit 1645
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674