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 .
Claims 21-33 are presented for examination.
The amendments and affidavit filed on 06/11/2025 have been received and entered.
Response to Arguments
Applicant’s arguments and affidavit have been noted. Applicant in his remarks argues that “the cited references, taken alone, or in any combination, do not teach or suggest the recited feature of amended independent claim 21. Further, Declaration °25 provides data that illustrates the improved stability of the first composition comprising the proton pump inhibitor at a pH of 12 or higher compared to lower pHs. Therefore, it cannot be assumed that the cited references teach or suggest, wherein the first and the second compositions are configured to be stored up to 12 months or greater, as recited in amended independent claim 21, at least because the cited references do not consider a proton pump inhibitor solution at a pH of 12, much less between 12 and 12.5”. It is the examiner’s position that Phillips (‘432) teaches present disclosure provides a kind of multiple dose suspendible product to be used to use one or more proton pump inhibitors. For example, in described first compartment, load pH and be about 7, about 6.5 to about 15 or about 8 PPI to about 12 the suspension; And in described second compartment, loading pH is about 6, about 5 to about 10 or about 6.5 to about 8.5 buffer solution. See Para [00321]. Therefore Phillips (‘432) teaches proton pump inhibitors omeprazole being as one of them in a liquid formulation at the pH being 12 and higher. The advantages taught in the applicants affidavit are the expected property of the composition of prior art, which uses the same components and the pH of 12 and over as the claimed in the instant application. Applicant in his remarks further argues that “ Phillips only considers that use of omeprazole when it is stored as a solid. With reference to a liquid formulation, however, Phillips instead considers proton pump inhibitors that possess high pika’s, such as rabeprazole. Rabeprazole has a pKa that is higher than the other common PPIs, such as omeprazole, by an order of magnitude, particularly considering pKa is measured on a logarithmic scale, as provided in Hellstrom, P., & Vitols, S. (2004). Choice of Proton Pump Inhibitor: Does it matter? Basic & Clinical Pharmacology & Toxicology, 106-111 (“Hellstrom”). Specifically, Hellstrom states:
Although pantoprazole (pKa 3.96) and rabeprazole (pKa 4.9) differ greatly
in terms of pKa, and activation rate, they induce the same degree of gastric acid
inhibition with similar IDso-values, which also holds true for lansoprazole (pKa
4.01), as well as omeprazole and esomeprazole (pKa 3.97)”. It is the examiner’s position the Phillips (‘432) in Para [0039] teaches that the compositions described herein can be liquid dosage form or unitary form. The limiting examples of appropriate liquid dosage form comprises solution, suspendible liquor, elixir, syrup, liquid aerosol etc. Phillips (‘432} in Para [0239] teaches that in one embodiment, can prepare the fluid composition that comprises water or other solvent, a PPI, one or more other PPI and buffer agent. Phillips (‘432) in para [00242] teaches that the mixed suspension composition comprises a PPI, one or more other PPI, one or more buffer agents, liquid medium (for example water, deionized water etc.) and one or more optional pharmaceutical excipients. This compositions, storage and be maintained at room temperature, cold preservation (for example about 5-10 ℃) temperature or cryogenic temperature and assign about 1,2,3,4,5,6,7,8,9,10,11 or time of 12 months in sealed container, demonstration wherein exists about 90%, about 92.5%, about 95% or about 97.5% an original PPI and/or one or more other PPI. It is also the examiner’s position that there is no evidence of record that omeprazole cannot be formed in a liquid solution based on the pKa. Furthermore, the examiner is not clear as how applicant is capable of making an omeprazole solution with a PKa that applicant is claiming to be low and not suitable for a liquid formulation.
In conclusion, the prior art is using omeprazole, which is taught by the prior art as a proton pump inhibitor. The prior art also teaches a liquid solution comprising a proton pump inhibitor at the claimed pH of over 12 and a buffering agent at the claimed range pH. Applicant is selecting one proton pump inhibitor and using it in a liquid formulation in combination with a buffering formulation. There is ample motivation from the prior art’s teachings to prepare the claimed composition in the absence of evidence to the contrary.
Claim Rejections - 35 USC § 103
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.
Claim(s) 21-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Phillips (US 20050054682) in view of Phillips (CN 101600432) and Smith et al. (WO 03106292) .
Phillips teaches the use of proton pump inhibitors in a liquid formulation. See the abstract and Para [0011]. The use of proton pump inhibitors, such as, omeprazole, pantoprazole and esomeprazole is taught in Para [0021]. The use of free base, a free acid, or a salt, hydrate, ester, amide, enantiomer, isomer, tautomer, polymorph, prodrug, or derivative of the claimed proton inhibitors is taught in Para [0039]. The treatment of duodenal ulcer, gastric ulcer, acid dyspepsia, gastroesophageal reflux disease (GERD), severe erosive esophagitis, poorly responsive symptomatic gastroesophageal reflux disease, heartburn, other esophageal disorders, and a gastrointestinal pathological hypersecretory condition such as Zollinger Ellison Syndrome is taught in Para [0013]. The example of buffering agents, such as, sodium hydroxide, sodium bicarbonate and sodium dihydrogen phosphate is taught in Para [0044]. The use of amino acids, such as cysteine is taught in para [0373] and Table 10. Phillips teaches that Non- limiting examples of suitable liquid dosage forms include solutions, suspension, elixirs, syrups, liquid aerosol formulations, etc. Compositions of the invention can be formulated for any method of delivery, for example oral, rectal, topical, or parenteral (e.g., subcutaneous, intramuscular, intravenous and intradermal or infusion) delivery. See Para [0058]. Phillips teaches that the Individual dosage units of this embodiment typically contain about 5 mg to about 100 mg. See Para[0060]. Phillips further teaches that PPI is mixed with a pre-made solution comprising buffering agent to achieve a desired final PP! concentration. Illustratively, the concentration of PPI in the solution can range from approximately 0.2 mg/ml to about 20 mg/ml, about 0.3 mg/ml to about 15 mg/ml, or about 0.4 mg/ml to approximately 10.0 mg/ml. See Para[0084]. Phillips teaches that the buffering agents are used to obtain the pH of about 6.0 or higher. See Para[0076]. The pH of 10.9 for proton pump inhibitors is taught in Paras [0385] and [0389]. The pH for sodium bicarbonate being between 4.6-10.9 is taught in Para [0441] and the pH for buffering product is taught to be 8-11. See para [0522]. Phillips teaches that liquid dosage forms can comprise one or more optional pharmaceutical excipients including suspending agents (for example, gums, xanthan, cellulose and sugars), humectants (for example, sorbitol), solubilizers (for example, ethanol, water, PEG and propylene glycol), surfactants (for example, sodium lauryl sulfate, Soans, Tweens, and cetyl pyridine), preservatives, antioxidants (for example, parabens, vitamins E and C, and ascorbic acid), anti-caking agents, and chelating agents (for example, EDTA). See Para [0085]. The use of flavoring agents is taught in Para [0087]. Phillips teaches that administration kits of IV proton pump inhibitor and oral parietal cell activator can be packaged in many various forms for ease of administration and to optimize packing and shipping the product. Such kits can be in unit dose or multiple dose form. See Para [0269]. Phillips teaches a suspension was prepared by mixing 8.4% sodium bicarbonate with omeprazole to produce a final concentration of 2 mg/ml to determine the stability of omeprazole solution after 6 months. See Para [0271]. Phillips differs from the claimed invention in specifically teaching a first and second composition, the specific viscosity and osmolality and a kit with plural compartments.
Phillips (‘CN) teaches a pharmaceutical composition comprising combinations of proton pump inhibitors, salt forms thereof or related compounds and at least one other pharmaceutically active agent. Methods of using such compositions, including methods of and an apparatus for administering such compounds. See the abstract. Phillips (CN) teaches a device with a plurality of compartments, it comprises (a) a plurality of compartments, one of them compartment comprises pharmaceutically active agents, optional protective cushion agent and/or optional thickening agent, second compartment comprises one or more sweeting agent, disintegrating agent, additive, buffer agent or thickening agent, and the described preparation in the described compartment can present the form of the dried forms of suspension, liquid, solution or water or other suitable liquid construction. Phillips ((CN) also teaches the pH of 12 and higher for proton pump inhibitors and pH of 8-8.4 for sodium bicarbonate. See Para [(00419} and [0031]. Smith et al. teach container for mixing two substances, the container having a first compartment, which can hold a first substance, the first compartment having an opening and a mixer portion releasably attached relative to the first compartment, the mixer portion comprising a second compartment which can hold a second substance, the second compartment having at least one opening, to allow the substances to be combined in the second compartment. See the abstract. Smith teaches that he means to allow the contents of the second compartment to mix with the first compartment may comprise a breakable membrane, a peel away membrane and the like. The membrane may comprise paper, plastic or similar ingredients. The use of threaded cap is taught in Figures 5 and 6. It would have been obvious toa person skilled in the art to combine the first composition and the second composition of the claimed invention motivated by Phillips (682) and Phillips (“CN), which teach a suspension of proton inhibitors at the claimed pH and sodium bicarbonate at the claimed pH that are mixed together. The use of a buffering agent, sodium hydroxide and antioxidant is also used in combination with the claimed proton pump inhibitors. I t would have been obvious toa person skilled in the art to arrive at the claimed viscosity and osmolality, considering that Phillips (682) teaches all the components of the claimed invention. There is no evidence of record that applicant is using any other components than Phillips to arrive at the claimed viscosity and osmolality. Phillips ((CN) teaches a kit with different compartments to house pharmaceutical active agents and the buffering agents separately. Smith teaches a container with a breakable membrane and a threaded cap having two compartments. Applicant has presented no evidence to the unexpected or unobvious nature of the claimed invention, and as such claims 21-33 are properly rejected under35 U.S.C. 103 (a).
THIS ACTION IS MADE FINAL. 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 ZOHREH A FAY whose telephone number is (703)756-1800. The examiner can normally be reached Monday-Friday 9:30AM-6:00.
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/ZOHREH A FAY/Primary Examiner, Art Unit 1617