DETAILED ACTION
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 .
Applicant canceled claims 19-23, 25 and 29. The newly added claims 33-42 still conform to the invention previously elected by applicant (i.e., an invention of Group III which is drawn to a method of treating a nitrogen retention disorder or other disorder by preprandially administering a taste masked phenylbutyrate to a subject).
It is to be noted that even though applicant labeled the new claim 42 as a withdrawn claim, claim 42 was examined along with other new claims 33-41 in this Office Action. Applicant thus need to change the claim identifier for claim 42.
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.
Claim Objections
Claim 33 is objected to because of the following informalities: on the last line, applicant need to delete “or”. Appropriate correction is required.
Claim 40 is objected to because of the following informalities: on line 2, applicant need to change “355 pm” to --- 355 mm ---. 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 33-42 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.
First of all, in claim 33, applicant recite “where the nitrogen retention disorder is selected from the group consisting of hyperammonemia, . . . . homocitrullinuria syndrome, maple syrup urine disease, . . . Parkinson’s disease, . . . hepatocellular carcinoma, and hepatic encephalopathy.”. However, many disorders listed in claim 33 do not belong to the category of nitrogen retention disorders (see for example, maple syrup urine disease, Parkinson’s disease, prostate cancer, etc.), thus rendering the scope of instant claim 33 indefinite. Applicant need to make appropriate corrections.
Secondly, on line 1 of claim 33, applicant need to change “or a disorder” to --- or other disorder that can be treated with phenylbutyrate --- (as previously recited in canceled claim 19) since it has to be disorder that can be treated with phenybutyrate, not any disorder.
Thirdly, it is unclear to the Examiner what applicant mean by “radiation protection” on the last line of claim 33 as it is the Examiner’s understanding that the term “radiation protection” does not refer to a disorder. Appropriate correction or clarification is necessary.
Claim 40 is 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.
Instant claim 40 recites that at least 95% of the composition has a particle size smaller than 335 mm as determined by sieving. However, in order to make the meaning of claim 40 clear, applicant need to first state that the composition is formulated as a plurality of particles and then recite that at least 95% of the particles have a particle size smaller than 335 mm as determined by sieving,. Appropriate correction is required.
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.
Claim(s) 33-42 are rejected under 35 U.S.C. 103 as being unpatentable over Appel et al (US 2017/0266115 A1) in view of Nakano et al (“Effect of food on the pharmacokinetics and therapeutic efficacy of 4-phenylbutyrate in progressive familial intrahepatic cholestasis”, Scientific Reports, vol.9(1):17075 (November 19, 2019) 12 pages).
Appel teaches (abstract, [0010], [0013], [0014] and [0072]) administering an effective amount of a palatable sodium phenylbutyrate (“NaPB”) composition that contains 5-50 wt.% of a taste-mask coating and 15-60 wt.% of NaPB for the treatment of inborn errors of metabolism, such as maple syrup urine disease or urea cycle disorders, or neurodegenerative disorders, such as Parkinson’s disease or dystonia (all of which teach instant disorders listed in claim 33).
With respect to instant limitation “50-75% by total weight of phenylbutyrate”, as shown above, Appel’s NaPB composition contains 15-60 wt.% of NaPB, and such range overlaps with instant range 50-75 wt.%, thus rendering instant range prima facie obvious. In the case “where the [claimed] ranges overlap or lie inside ranges disclosed by the prior art,” a prim facie case of obviousness would exist which may be overcome by a showing of unexpected results, In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). Furthermore, with respect to instant limitation “8-25% by total weight of a taste mask”, Appel’s NaPB composition contains 5-50 wt.% of a taste-mask coating, and such range overlaps with instant range 8-25 wt.% of claim 33 as well as with instant ranges of claims 41 and 42 (8-10 wt.% and 15-18 wt.%, respectively), thus rendering instant ranges of claims 33, 41 and 42 prima facie obvious. In re Wertheim, supra.
With respect to instant limitation “wherein the composition is administered prepandial”, Appel teaches ([0182]) that the administration of the taste-masked NaPB may be in a fasted or fed state, but does not explicitly state that the administration has to be preprandial. Nakano teaches (abstract, pg.6, last paragraph) that food intake before the administration of NaPB markedly reduces the PB systematic exposure and could eliminate its therapeutic efficacy. Nakano thus concludes that preprandial oral administration of NaPB is needed to maximize its potency and decrease the clinically effective dose to patients with urea cycle disorders. Thus, it would have been obvious to one skilled in the art to administer Appel’s taste masked NaPB composition preprandial with a reasonable expectation of maximizing its potency and decreasing the clinically effective dose of NaPB to patients with nitrogen retention disorder (such as maple syrup urine disease, urea cycle disorders, Parkinson’s disease or dystonia). Thus, Appel in view of Nakano renders obvious instant claims 33, 41 and 42.
With respect to instant claims 34 and 35, Appel teaches ([0011]) that its composition can be formulated as a plurality of spray-layered particles or beads for oral administration. Appel teaches that such spray-layered particles have a seed core onto which a drug layer (containing NaPB) is coated followed by a taste-mask coat layer. Appel further teaches ([0026]) that its composition includes 1-50 wt.%, for example, 10-20 wt.%, by total weight of a seed core. Appel’s range 10-20 wt.% overlaps with instant range of claim 35 (10-17 wt.%), thus rendering instant range prima facie obvious. In re Wertheim, supra. Thus, Appel in view of Nakano renders obvious instant claims 34 and 35.
With respect to instant claim 36, Appel teaches ([0021]) that its drug layer further include 3-10 wt.% by total weight of a binder. Appel’s range 3-10 wt.% overlaps with instant range (5-7 wt.%) for the amount of binder, thus rendering instant range prima facie obvious. In re Wertheim, supra. Thus, Appel in view of Nakano renders obvious instant claim 36.
With respect to instant claim 37, Appel teaches ([0022]) that its drug layer further includes 0.1-1 % by total weight of a plasticizer, and such range overlap with instant range 0.5-1 wt.% for the amount of plasticizer, thus rendering instant range prima facie obvious. In re Wertheim, supra. Thus, Appel in view of Nakano renders obvious instant claim 37.
With respect to instant claim 38, Appel teaches ([0010], [0019]) that examples of its taste-mask coating include a polymer formed from dimethylaminoethyl methacrylate, butyl methacrylate and methyl methacrylate (e.g., a cationic polymer such as Eudragit EPO). Thus, Appel in view of Nakano renders obvious instant claim 38.
With respect to instant claim 39, Appel teaches ([0024]) that its taste-mask coating can include less than 8% of a hydrated magnesium silicate, e.g., talc (instant anti-tacking agent of claim 39 – see present specification, pg.8, line 15). The range less than 8% overlaps with instant range 1-7 wt.% of claim 39, thus rendering instant range prima facie obvious. In re Wertheim, supra. Thus, Appel in view of Nakano renders obvious instant claim 39.
With respect to instant claim 40, Appel teaches (claim 6 and [0062]) that its taste-mask coated beads (or particles) may have a volume-based particle size distribution in which 90% of the beads in the composition are smaller than about 500 mm. Under such guideline given by Appel, instant limitation as to at least 95% of the composition having a particle size smaller than 355 mm (as determined by sieving) would have been obvious to one skilled in the art before the effective filing date of the claimed invention since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233. Thus, Appel in view of Nakano renders obvious instant claim 40.
Response to Arguments
Applicant argue that the new claims 33-41 are allowable over the cited references as neither Appel nor Nakano teaches preprandial administration of taste-masked phenylbutyrate for treating the recited nitrogen retention disorders. The Examiner believes that applicant’s such argument was already answered above.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Kwon can be reached on 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SIN J LEE/
Primary Examiner, Art Unit 1613
October 31, 2025