DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . The submission filed on 06/28/2024 has been entered. Claims 1-11 are pending in this application and are currently under examination.
Priority
This application is a DIV of 17/454,336 filed on 11/10/2021, now PAT 12059461, which is a DIV of 16/482,349 filed on 07/31/2019, now PAT 11197921, which is a 371 of PCT/US18/15907 filed on 01/30/2018 which claims benefit of US PRO No. 62/452,522 filed on 01/31/2017.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed application, Application No. 62/452,522, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Claims 1-11 recite “at a temperature in a range from 2 to 25°C and a pH of 7.0 or less, or a range from 2 to 10°C and a pH of 7.7 or less to form”, “in a range from 2 to 23°C”, and/or “in a range from 8 to 12°C”, which are not disclosed in the prior-filed Application No. 62/452,522. Thus, the priority date of claims 1-11 is 01/30/2018.
Information Disclosure Statement
Two information disclosure statement (IDS) filed on 09/25/2024 have been considered.
Claim Objections
Claim 10 is objected to because of the following informalities: In claim 10, change the incorrect recitation “the protein is a carrier protein selected” (line 1) to “the carrier protein is selected” to tie with preceding “a carrier protein” in claim 1. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-11 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 2, 3, and 7-11 depend from claim 1.
The term “strong reducing agent” in claims 1 and 4-6 is a relative term which renders the claim indefinite. The term “strong” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Also, the reducing agent appears to be additional to cyanoborohydride. Thus, Applicant is advised to change the recitation “a strong reducing agent” (line 7 of claim 1) to “an additional reducing agent”; to replace the recitation “step b) is adding a strong reducing agent” (claim 4) with “step b) is included for adding the additional reducing agent”; and to change the recitation “strong” (line 1 of claims 5 and 6) to “additional”.
Claim Rejections - 35 USC § 102/103
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
(I) Claims 1-11 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Hausdorff et al. (US 2007/0231340, Oct. 4, 2007, hereinafter referred to as Hausdorff ‘340, also listed in IDS filed on 09/25/2024).
With regard to the structural limitations “a method comprising: a) reacting an activated serotype 3 polysaccharide with a carrier protein (or tetanus toxoid, diphtheria toxoid, or CRM197) in an aqueous buffer in the presence of a cyanoborohydride salt (or sodium cyanoborohydride) at a temperature in a range from 2 to 25°C (or from 2 to 23°C) and a pH of 7.0 or less (or a pH from 6.0 to 7.0) to form a conjugate reaction mixture; b) adding an additional reducing agent (or sodium borohydride); and c) purifying the conjugate reaction mixture (or by ultrafiltration) to remove residual reactant including free cyanide ions” (claims 1-8, 10, and 11), and (in the presence of a cyanoborohydride salt at a temperature in a range from 8 to 12°C and a pH of 7.0 or less or a range from 2 to 10°C and a pH of 7.7 or less” (claims 1 and 9):
Hausdorff ‘340 disclosed Preparation of Serotype 3 Pneumococcal Saccharide-CRM197 Conjugate (Example 4). Bottles of co-lyophilized saccharide/protein material were brought to room temperature and resuspended in 0.1M sodium phosphate buffer, pH 7.0. The pH was adjusted to 6.5 and then a 0.5 molar equivalent of sodium cyanoborohydride was added. The reaction was incubated at 37° C for 48 hours. Following the cyanoborohydride incubation, the reaction mixture was diluted with cold 5 mM succinate/0.9% saline buffer. Unreacted aldehydes were quenched by the addition of sodium borohydride and incubation at 23 ° C for 3-6 hours. The reaction mixture was transferred through a 0.45-5 μm prefilter into a retentate vessel. The reaction mixture was diafiltered 30x with 0.1M phosphate buffer (pH 9), 20x with 0.15M phosphate butter (pH 6), and 20x with 5 mM succinate/0.9% saline (page 14/26, [0117-0121]). Preparation of Serotype 1 Pneumococcal Saccharide-CRM197 Conjugate (Example 2). Purified polysaccharide was activated by oxidation in the presence of sodium periodate at 2-8° C. Bottles of lyophilized material were brought to room temperature and resuspended in CRM197 solution at a saccharide/protein ratio of 2:1. To the saccharide/protein mixture 1M sodium phosphate buffer was added to a final 0.2M ionic strength and a pH of 7.5, then sodium cyanoborohydride was added. The reaction was incubated at 23° C. for 18 hours, followed by a second incubation at 37° C for 72 hours. Following the cyanoborohydride incubations, the reaction mixture was diluted with cold saline followed by the addition of 1M sodium carbonate to adjust the reaction mixture to pH 9.0. Unreacted aldehydes were quenched by addition of sodium borohydride by incubation at 23° C for 3-6 hours (page 13/26, [0091-0094]). The degree of oxidation (DO) of Serotype 3 Pneumococcal Saccharide by sodium periodate at 4° C is consistently higher than at 25° C as shown in Table 3 (page 11/26, [0069]).
Thus, these teachings of Hausdorff ‘340 anticipate Applicant’s claims 1-8, 10, and 11 because (a) the cold 5 mM succinate/0.9% saline buffer after incubation at 37° C for 48 hours in the pH 6.5 conjugation step of the Serotype 3 Pneumococcal Saccharide-CRM197 preparation would bring down the temperature to 23° C for subsequent addition of sodium borohydride and (b) incubation at 37° C and/or 23° C is carried out in the conjugation step with aqueous sodium cyanoborohydride, described above. Or, in an alternative, skilled artisan would substitute the 37° C in the pH 6.5 conjugation step of the Serotype 3 Pneumococcal Saccharide-CRM197 preparation with 23° C to facilitate subsequent sodium borohydride quenching at 23° C. Also, it would be obvious to skilled artisan for carrying out cyanoborohydride incubation at 2 to 8° C, required by claims 1 and 9, because other chemical reaction, such as polysaccharide activation by sodium periodate, is more effective at 4° C than at 25° C as shown in Table 3, and has been performed at 2 to 8° C, descried above.
(II) Claims 1-11 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Smith et al. (WO 2018/156468, published on August 30, 2018, PCT filed on February 20, 2018, and benefited by US PRO 62/463,220 24 filed on February 24, 2017, hereinafter referred to as Smith ‘468, also listed in IDS filed on 09/25/2024). The applied reference has a common Applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
With regard to the structural limitations “a method comprising: a) reacting an activated serotype 3 polysaccharide with a carrier protein (or diphtheria toxoid, or CRM197) in an aqueous buffer in the presence of a cyanoborohydride salt (or sodium cyanoborohydride) at a temperature in a range from 2 to 25°C (or from 2 to 23°C; or 8 to 12°C) and a pH of 7.0 or less or a range from 2 to 10°C and a pH of 7.7 or less (or a pH from 6.0 to 7.0) to form a conjugate reaction mixture; b) optionally, adding an additional reducing agent (or sodium borohydride); and c) purifying the conjugate reaction mixture (or by ultrafiltration) to remove residual reactant” (claims 1-11):
Smith ‘468 disclosed Conjugation of S. pneumoniae serotype 3 polysaccharides to diphtheria toxin fragment B (DTFB) Carrier Protein using Reductive Amination in Aqueous Solution (Example 3). Preparation of Serotype 3-DTFB (ST3-DTFB) Conjugate for Mouse Immunogenicity Studies: The periodate-oxidized polysaccharide was mixed with DTFB prepared as described in Example 1 (from purified CRM197, using multimodal anion exchange chromatography) at a polysaccharide to protein mass ratio of 0.6: 1. Potassium phosphate, pH 6.4 and nickel chloride were added to final concentrations of 145 mM and 2.2 mM, respectively. Sodium cyanoborohydride to approximately 1-2 molar equivalents was then added. The reaction was protected from light and carried out over a period of 120 hours at 2-8°C. The mixture was then dialyzed against 2 changes of 25 mM potassium phosphate 10 buffer, pH 6.4, 0.3 M sodium chloride at 2-8°C for a total of 14 - 18 hours. Preparation of Serotype 3-DTFB Conjugate for Infant Rhesus Monkey Immunogenicity Study: Activated polysaccharide solution was blended with water and 1.5 M potassium phosphate, pH 7.0. Purified DTFB was 0.2-micron filtered, and then combined with the buffer-adjusted polysaccharide solution at a polysaccharide to protein mass ratio of 1.3: 1. The solution was then 0.2 micron filtered. Nickel chloride was added to the batch to a final concentration of approximately 2 mM using a 100 mM nickel chloride stock solution. Sodium cyanoborohydride (2 moles per mole of polysaccharide repeating unit) was then added. The batch was allowed to react for approximately 120 hours at approximately 10°C to maximize consumption of polysaccharide and protein. Following the conjugation reaction, sodium borohydride (1 mole per mole of polysaccharide repeating unit) was added. 1.5 M potassium phosphate, pH 6.0 was later added. The batch was then concentrated and diafiltered against 10 mM L-histidine in 150 mM sodium chloride, pH 7.0 at 2-8°C using a 300 kDa NMWCO tangential flow ultrafiltration membrane (page 35/82, lines 20-33; page 36/82, lines 3-10 and 15-33; page 37/82, lines 1-18).
Thus, these teachings of Smith ‘468 anticipate Applicant’s claims 1-11.
Conclusion
No claims are allowed.
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/YIH-HORNG SHIAO/Primary Examiner, Art Unit 1691
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