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 .
DETAILED ACTION
Claims 1 and 4-10 are currently pending and an amendment to the claims filed on 12/31/2025 is acknowledged. Since claim 10 has been withdrawn, claims 1 and 4-9 are being examined on the merits.
Withdrawn rejections:
Applicant's amendments and arguments filed 12/31/2025 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below are herein withdrawn.
The following rejection and/or objection are either reiterated or newly applied. They constitute the complete set of rejection and/or objection presently being applied to the instant application.
New Grounds of the Rejections – as necessitated by amendment
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.
Claim 1 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.
Claim 1 recites “polymer – 10-25% by weight (60-150mg)”. However, it is not clear whether the part covered by parentheses is a limitation or not. Here “10-25%” could be of 1000mg and represent a range of 100 to 250mg. Therefore, the parenthetical phrase causes confusion to determine clarity of scope. In this regard, please see that “parenthetical expressions are not permissible which do not contribute to clearness or exactness in stating Applicant’s invention” (Ex parte Cahill, 1893 C. D., 78; 63 O. G., 2125). Appropriate correction is requested.
Claim Rejection - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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.
Claims 1 and 4-9 remain rejected under 35 U.S.C. 103 as being unpatentable over Roberts et al. (US2008/0227830A1) in view of Li ( US2016/0354315A1).
Applicant claims the below claim 1 filed on 12/31/2025:
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Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a medical/pharmaceutical orthostatic hypotension research scientist, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from orthostatic hypotension medicine, pharmacy, physiology and chemistry— without being told to do so.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art (MPEP 2141.01); Ascertainment of the difference between the prior art and the claims (MPEP 2141.02); and Finding of prima facie obviousness Rational and Motivation (MPEP 2142-2143)
Roberts discloses droxidopa and pharmaceutical composition thereof for the treatment of neurally mediated hypotension (title) such as Parkinson’s disease ([0032]); the composition is provided in the form of solid dosage such as wafer-shaped tablet (including effervescing) ([0096]) wherein the composition comprises 1mg-3g (e.g., about 60mg-about 800mg, about 100mg to about 400mg) droxidopa ([0117]-[0118] and [0121]) which reads on the claimed droxidopa, polymers such as cellulose, e.g., HPMC ([0099]) which reads on the claimed polymer, fillers such as microcrystalline cellulose ([0103]) which reads on the claimed diluent and talc ([0103]) which reads on the claimed glidant ([0103]), lubricant such as magnesium stearate ([0103]) which reads on the claimed lubricant; the solid dosage form (e.g., tablet ([0095]) may also be sustained release ([0093] and [0105]) wherein the time to complete disintegration can be an extended period of time, such as about 6 hours ([0108]); and the composition is administered twice a day ([0111]); although Roberts does not expressly teach viscosity K200M of HPMC, it would not be inventive without evidence that HPMC K200M provides superior effects in sustained release profile as compared with other lower viscosity HPMC (instant claims 1 and 8 (in part), and claims 4 and 9). Further, Roberts discloses the ratio of droxidopa to the one or more additional compounds is in the range of about 20:1 to about 3:1 ([0121]).
However, Roberts does not expressly teach gas generating agent of instant claim 5, effervescent agent of instant claim 6, and glidant of instant claim 7. The deficiencies are cured by Li.
Li discloses a stable solid pharmaceutical dosage form for oral administration wherein the form includes droxidopa ([0091]) and polymers such as HPMC ([0075]); the dosage form (e.g., tablet) can release the drug content in a controlled manner (e.g., sustained release) and can have increased residence in the gastrointestinal tract (abstract, [0069], [0083], [0084], Fig. 2B, etc.) and in an effervescent manner (abstract, [0069] and [0111]); to do so, the dosage form comprises a gas-generating component such as sodium bicarbonate and an organic acid (e.g., citric acid, tartaric acid) ([0111]-[0112]); and further, the dosage form contains talcum (=talc) as a conventional auxiliary substance ([0114]) which reads on the claimed glidant and magnesium stearate ([0114]) which reads on the claimed lubricant. Further, Li discloses the drug form provides increased residence in the gastro intestinal tract ([0084]) (instant claims 5-7).
It would have been obvious to further add the ingredients of Li to the composition of Roberts in order to make the tablet in effervescent form as taught by Li.
Although Roberts/Li do not expressly teach the claimed amounts of polymer, additives, and tablet weight, Roberts teach the ratio of droxidopa to additives. Further, in the relevant field, the amounts of additives would determine from the standpoint of the ordinary artisan. Accordingly, depending on the intended purpose/effects, type of formulation, relationship with other ingredients including active drug, etc., such amounts would be optimized or adjusted unless there is no criticality of the claimed ranges. In this regard, please see MPEP 2144.05 (II)(A): Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.
Although Roberts/Li do not expressly teach floating lag time and sustained delivery over 10-12 hours of instant claim 1, Roberts teaches sustained release (e.g., [0093] and [0105]) with a delayed release coating materials of HPMC ([0099] and [0104]), and thus, the claimed times in a sustained manner would be optimized depending on the intended effects/purpose.
Further, the applied art does not expressly teach the claimed embodiment of instant claim 1, and however, one of ordinary skill would be motivated to provide such embodiments this because a reference is analyzed using its broadest teachings. MPEP 2123 [R-5].
Where, as here, the specific combination of features claimed is disclosed within the broad teachings of the reference but the references (Roberts and/or Li) do not disclose the specific combination of variables (for example, various additives and/or excipients as claimed), in a specific embodiment or in a working example, “picking and choosing” within several variables does not necessarily give rise to anticipation. Corning Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989).
However, "when a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious". KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007)(quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976). "[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious", the relevant question is "whether the improvement is more than the predictable use of prior art elements according to their established functions." (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that "[a] person of ordinary skill is ... a person of ordinary creativity, not an automaton." Id. at 1742.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to rearrange the disclosed elements and embodiments of (from Roberts, effervescent tablet containing a drug droxidopa, cellulosic polymer such as HPMC, lubricant, and from Li, effervescent tablet containing e.g., droxidopa, effervescent agents of sodium bicarbonate and citric/tartaric acid, and glidant such as talc, etc.) to prepare the claimed composition. Such a rearrangement by a person of ordinary skill in the art who is not an automaton to yield the instantly claimed invention within the purview of the ordinary skilled artisan upon reading the applied art and would yield predictable results.
Further, the applied art does not expressly teach the properties of floating lag time and buoyancy time of instant claim 8. However, the applied art in combination teaches the claimed effervescent tablet containing the elements, and therefore, the properties would be implicit. In this context, please see case law stating that The claimed features are a natural result of the combination of elements. Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1371 (Fed. Cir. 2008). (inherency is limited when applied to obviousness and is present only when the limitation at issue is the “natural result” of the combination of prior art elements; quoting In re Oelrich, 666 F.2d 578, 581 (CCPA 1981)). See also MPEP 2112. Persion Pharms. LLC v. Alvogen Malta Operations LTD., 945 F.3d 1184, 1191, 2019 USPQ2d 494084 (Fed. Cir. 2019), “where the court stated that a proper finding of inherency does not require that all limitations are taught in a single reference, and that inherency may meet a missing claim limitation when the limitation is “the natural result of the combination of prior art elements.” That is, the court found that pharmacokinetic limitations of the asserted claims were inherently met by combining prior art references because the limitations were necessarily present in the prior art combination.
This rejection is based on the well-established proposition of patent law that no invention resides in combining old ingredients of known properties where the results obtained thereby are no more than the additive effect of the ingredients, In re Sussman, 1943 C.D. 518. From MPEP 2143 A: “…all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at ___, 82 USPQ2d at 1395; Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson ’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950).”
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the combined references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments have been fully considered, but are not persuasive.
Applicant argues that Roberts fail to disclose HPMC K200M, effervescent agent and glidant, and concentration; in Roberts, dosage form is designed to disintegrate rapidly from 10 minutes to about 6 hours while the claimed tablet may release droxidopa in a sustained manner for 10-12 hours, thereby reducing dosing frequency and improving patient adherence, and Li also discloses the tablet is made of a materials that dissolves between 1-10 minutes and the substrate dissolves in 2-60 seconds; and the claimed data shows unexpected sustained release over 10-12 hours (see Tables 8, 9 and 11 of instant specification).
The Examiner responds that it is well known that HPMC is used as a delayed releasing agent as taught by the applied art; and the higher viscosity of HPMC, the lower the release rate of the drug because HPMC K200M provides a more controlled (slower) drug release rate compared to K100M due to its higher viscosity and stronger gel layer formation. Thus, the claimed invention using selection of high viscosity HPMC K200M is obvious over the applied art and alleged unexpected result would be expected. Further, Li teaches gas generating agent, effervescent agent and glidant as noted above. Please note that [O]ne cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. In reKeller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In reMerck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). MPEP 2145.
And the applied art of Roberts ([0093] and [0103]) and Liu (abstract, [0069], [0083], etc.) clearly discloses the dosage form can be provided in a sustained release of droxidopa. Thus it would be obvious to provide intended sustained release for 10-12 hours with high viscosity e.g., HPMC K200M release controlling agent as taught/suggested by the applied art because high viscosity HPMC creates a viscous gel layer upon contact with water that controls drug release, as taught/suggested by the applied art.
In light of the foregoing, applicant’s arguments are not persuasive.
Citation of Pertinent Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. They may be used in the next Action:
Roy et al., “Formulation and design of sustained release matrix tablets of metformin hydrochloride: Influence of hypromellose and polyacrylate polymer,” International Journal of Applied and Basic Medical Research, Jan-Jule 2013, vol. 3, issue 1, pp. 55-63 – higher viscosity HPMC K200M provides a more controlled (slower) drug release rate compared to K100M due to its higher viscosity and stronger gel layer formation.
Peroutka et al. (US8,158,149B2) discloses Droxidopa (=Threo-DOPS)-containing controlled release formulation wherein the formulation contains HPMC as a coating/matrix material and the formulation releases droxidopa in the sustained manner over at least 8 hours or between about 6 to about 24 hours (claims 1 and 13 of Peroutka).
Conclusion
All of the examined claims 1-9 are rejected.
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 KYUNG S CHANG whose telephone number is (571)270-1392. The examiner can normally be reached M-F 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Yong (Brian-Yong) S Kwon can be reached at 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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/KYUNG S CHANG/ Primary Examiner, Art Unit 1613