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 . 1
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on has been entered.
Status of the Claims
Claims 15-16, 18, 20, 30-35 and 37-44 are pending and are under examination.
Response to Arguments
Applicant's arguments dated April 7, 2025 with regard to the rejections of claims 15-16, 18, 20, 30-35 and 37-44 as being obvious over Rajpal et al. in view of Rawas-Qalaji et al., as evidenced by Nibha and Pacholi have been fully considered but they are not persuasive. Claims 15-16, 18, 20, 30-35 and 37-44 remain rejected.
Maintained 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.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicants are advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 15-16, 18, 20, 30-35 and 37-44 remain rejected under 35 U.S.C. 103 as being unpatentable over Rajpal et al. American Journal of Emergency Medicine (2010) 28, 143–150 in view of Rawas-Qalaji et al. (AAPS PharmSciTech 2006; 7 (2) Article 41), as evidenced by Nibha and Pacholi “An Overview on: Sublingual Route for Systemic Drug Delivery,” Published April 2012. www.ijrpbsonline.com (Year: 2012).
The cited prior art has been previously cited by the Examiner.
Claims 15 and 32 are directed to a composition and method for treating symptoms of exposure to organophosphates (OPs) in a subject in need thereof, comprising:
providing a composition including 1 to about 20% [w/w] of atropine sulfate and at least one pharmaceutically acceptable excipient, the composition formulated as a tablet for rapid disintegration and absorption into systemic circulation within an oral cavity of the subject after buccal or sublingual administration; and administering the composition to the subject, wherein the rapid disintegration is full disintegration of the tablet and occurs in less than about a minute in the oral cavity of the subject.
Claim 15 is directed to the composition wherein the at least one pharmaceutically-acceptable excipient is selected from the group consisting of a filler, a superdisintegrant, and a lubricant.
Claim 32 is directed to the method of treating symptoms of exposure to OP in a subject providing the claimed composition of atropine sulphate, with a composition as claimed in claim 15.
Accordingly, a proper rejection will comprise a teaching of
treating organophosphate poisoning
with a composition (tablet), comprising pharmaceutically acceptable excipient(s) formulated for rapid release and absorption into systemic circulation (within an oral cavity of the subject) in buccal or sublingual formulations.
Regarding claims 15 and 32 and the necessity of administering a sublingual (SL) formulation for the treatment of organophosphorus (OP) pesticide poisoning, Rajpal discloses a novel atropine sulfate (AS) sublingual (SL) formulation (injection) to a subject in need of organophosphate poisoning, 2 milligrams per 0.1 mL, a concentration that falls within that claimed, see abstract.
Rajpal describes the advantages of SL administration in terms of better bioavailability, rapid onset of action and early atropinization, see abstract and Conclusions section, page 149.
Rajpal discloses SL route of administration is receiving attention because “it avoids the first pass of metabolism of the drug, allowing it to enter the blood stream earlier than intramuscular or oral route.” See page 148, Section 4 discussion, column 1. Rajpal discloses its results provide the first evidence of the clinical effects and blood levels of sublingual atropine, Id. Rajpal discloses “Enhanced absorption from the sublingual route is because of its high perfusion, and the venous drainage from glossal/sublingual region to the large central veins of neck may increase the transport of injected drug to the muscarinic receptors of heart.” Id. .
Further, noting the advantages of SL administration of atropine to treat organophosphate poisoning, Rajpal teaches SL administration is a safe and efficacious procedure with the potential as an alternative to conventional IM injection, particularly in case of chemical terrorism scenario where hundreds of victims may require immediate atropinization simultaneously, see abstract.
Rajpal teaches presently, there is no strategy in place for mass casualty at the field level because the intravenous or intramuscular routes are either not practical or may be very slow in eliciting the therapeutic response in field conditions (page 144 columns 1-2). Thus, Rajpal’s solution of the SL route will address this need.
Although teaching the limitations of treating organophosphate poisoning (OP) sublingually with atropine sulfate as claimed, Rajpal does not teach 1) a sublingual tablet, 2) does not explicitly recite the claimed concentration range of 1-20 % w/w and 3) does not explicitly recite the limitation of the tablet dissolving in under a minute.
However, one of ordinary skill in the art would have a reasonable expectation of success in arriving at the claimed invention because: 1) sublingual tablets are known in the art to achieve rapid dosing while avoiding first pass metabolism drugs (allowing rapid entry into the blood stream as opposed intramuscular or oral routes) as evidenced by Nibha 20122; 2) known doses of atropine sulfate per Rajpal (2 to 4 mg of atropine sulphate for unit doses, see page 144, first column last paragraph), are routinely formulated into SL tablets of 150 mg total weight, that falls within the claimed 1-20% concentration) and 3) the limitation of disintegration of occurring in less than a minute in the oral cavity of the subject where sublingual are known to be dissolved in less than a minute as taught by Rawas-Qalaji.
Regarding the first point of obviousness of a sublingual tablet comprising a filler (microcrystalline cellulose), a super disintegrant (hydroxypropyl methylcellulose) and a lubricant (magnesium stearate), per claims 15 and 32, Rawas-Qalaji teaches fast-disintegrating sublingual tablets for the treatment of an emergent situation (anaphylactic shock) that requires immediate release of a drug to a subject, (similar to the situation of organophosphate poisoning), see abstract.
Regarding the limitations of the claimed invention of “a filler, a superdisintegrant, and a lubricant, the composition formulated as a tablet for rapid disintegration and absorption into systemic circulation within an oral cavity of the subject,” Rawas-Qalaji teaches the following.
Rawas-Qalaji teaches its tablets were designed to be a fast-disintegrating sublingual “tablets that disintegrate or dissolve rapidly in the patient's mouth,” see page E1 column 1 bridging to column 2.
Rawas-Qalaji teaches its tablets were designed to be a fast-disintegrating sublingual “tablets that disintegrate or dissolve rapidly in the patient's mouth,” see page E1 column 1 bridging to column 2. (emphasis added). Rawas-Qalaji further teaches advantages of its tablets are that they:
are convenient for young children, the elderly and patients with swallowing difficulties, and in situations where potable liquids are not available. For these formulations, the small volume of saliva is usually sufficient to result in tablet disintegration in the oral cavity. The medication can then be absorbed partially or entirely into the systemic circulation from blood vessels in the sublingual mucosa. . . . The sublingual route usually produces a faster onset of action than orally ingested tablets and the portion absorbed through the sublingual blood vessels bypasses the hepatic first-pass metabolic processes. See page E1, column 2. (emphasis added)
As Rajpal discloses the benefits of sublingual route similar to those of Rawas-Qalaji, one of ordinary skill in the art would have a reasonable expectation of success in arriving at the claimed invention because of the equivalency between the two routes of sublingual administration to rapidly deliver medications to the systemic circulation and avoid hepatic first pass metabolism. It is noted that further advantages of dosing via a rapidly dissolving sublingual tablet as per Rajpal (over the liquid sublingual administration of Rajpal) where Nibha 2012 discloses sublingual tablets advantages include ease of administration; convenience in administration of drug and accurate dosing as compared to liquid formulations; good mouth feel vs bitter pills; fast dissolution of medicament and absorption for rapid, onset of action; provides advantages of liquid formulations in the form of solid dosage form, see page 6, column 1, Section Advantages.
Regarding the limitations of claim 15 and 32 and the filler, superdisintegrant and lubricant limitations of the tablet, Rawas-Qalaji teaches a formulation comprising a filler (microcrystalline cellulose), a superdisintegrant (hydroxypropyl cellulose), and lubricant (magnesium stearate) with an active ingredient (epinephrine) in concentrations (6 and 12%) that falls within the claimed percentage range of claim 32, see Table 1 of Rawas-Qalaji, page E2, reproduced below.
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Regarding the third point of obviousness and disintegration of less than a minute, Rawas-Qalaji teaches its tablets were designed to be a fast-disintegrating sublingual “tablets that disintegrate or dissolve rapidly in the patient's mouth,” see page E1 column 1 bridging to column 2. (emphasis added). Further, Rawas-Qalaji discloses in Figure 2 how its formulations of fast disintegrating tablets demonstrate they disintegrate in under a minute, (4 tablets dissolved in in less than 32.5 seconds). See Figure 2, page E5, column 1 top of column.
A PHOSITA following the teachings of Rajpal would have found it prima facie obvious to formulate atropine sulfate administered sublingually as a sublingual (SL) tablet as taught by Rawas-Qalaji as the prior art recognizes the need for rapid administration of drugs (including atropine sulfate) sublingually by alternatives formulations of injection and tablets.
The rationale to do so is as Rajpal discloses the benefits of a sublingual route are similar to those of Rawas-Qalaji, a PHOSITA would have a reasonable expectation of success in arriving at the claimed invention because of the equivalency between the two routes of sublingual administration to rapidly deliver medications to the systemic circulation and avoid hepatic first pass metabolism. It is noted that further advantages of dosing via a rapidly dissolving SL tablet as per Rajpal (over the liquid SL administration of Rajpal) where Nibha 2012 discloses SL tablets advantages include ease of administration; convenience in administration of drug and accurate dosing as compared to liquid formulations; good mouth feel vs bitter pills; fast dissolution of medicament and absorption for rapid, onset of action; provides advantages of liquid formulations in the form of solid dosage form, see page 6, column 1, Section Advantages.
Regard claim 39 and the limitations of microcrystalline cellulose, hydroxypropyl cellulose, and magnesium stearate, Table 1 of Rawas-Qalaji recites these specific excipients of claim 39.
In terms of claims interpretation, claims 15, 32 and 39 recite their formulations have the structural limitations of comprising sublingual atropine sulphate (as per Rajpal) and a composition (tablet), comprising pharmaceutically acceptable excipient(s) formulated for rapid release and absorption into systemic circulation (within an oral cavity of the subject) in buccal or sublingual formulations (as per Rawas-Qalaji). Therefore, prior art reciting these elements will teach the claimed invention (despite any lack of teaching of teaching of the functionally descriptive limitations of, wherein the rapid disintegration is full disintegration of the tablet and occurs in less than about a minute in the oral cavity of the subject.
Regarding claims 16 and 34, directed to the exposure to organophosphates is exposure to pesticides or nerve agents), Rajpal discloses the increased use of OP pesticides and terror groups using nerve agents underscores the need to develop safe and effective antidotes, i.e. atropine sulfate, see abstract.
Regarding claims 18, 32, 33 and 44 and the limitation of the at least 3 pharmaceutically acceptable excipients recited therein, Rawas-Qalaji teaches the filler microcrystalline cellulose, the super disintegrant hydroxypropyl cellulose and the lubricant, magnesium stearate, see Table 1 reproduced above.
Regarding claim 18, Table 1 of Rawas-Qalaji teaches low substituted hydroxypropyl cellulose, see above.
Regarding claims 20 and 37 and a cholinesterase reactivator, Rajpal teaches the co-administration of the cholinesterase re-activator, pralidoxime chloride, see page 144, first column, first full paragraph.
Regarding claims 30 and 35 (treating hypersalivation), Rajpal teaches that SLUDGE (salivation, lacrimation, urination, diaphoresis, gastrointestinal motility, emesis) symptoms are caused by organophosphate poisoning, see page 144, first column first paragraph
Regarding claim 31 and the limitations that the buccal/sublingual formulation results in rapid/full disintegration that occurs in less than a minute in the oral cavity of a subject, Rawas-Qalaji teaches the same formulation of rapidly disintegrating/ buccal/sublingual tablet with the same excipients as claimed. Therefore,
while Rawas-Qalaji does not expressly recite the limitation of claim 31, because Rajpal and Rawas-Qalaji teaches applicant’s claimed rapid release formulation, (and without any further defining structure limitations amounts of excipients and active for example to distinguish from the cited prior art), such rapid, full disintegration and complete release properties are deemed to be necessarily present in the claimed invention.
Regarding claim 38 and the limitations of wherein the composition comprises from about 20 to about 95 wt% of microcrystalline cellulose as the filler, from about 1 to about 15 wt% of hydroxypropyl cellulose as the super disintegrant, and from about 0.5 to about 3 wt% of magnesium stearate as the lubricant, these limitations are taught by Table 1 of Rawas-Qalaji, see page E2.
Regarding claim 40 and the limitation of wherein the pharmaceutical composition comprises 1 to 16 wt% of atropine sulfate, 70 to 90 wt% of microcrystalline cellulose, 8 to 10 wt% of hydroxypropyl cellulose, and 0.5 to 2 wt% of magnesium stearate, the concentration limitations of the excipients are taught by Table 1 of Rawas-Qalaji, see above.
Regarding claims 41-42 and administration of pralidoxime, Rajpal teaches the co-administration of the cholinesterase re-activator, pralidoxime, see page 144, first column, first full paragraph.
Regarding claim 43 and the treatment of the symptoms of exposure to organophosphate that include any symptom resulting from excessive acetylcholine activity in the subject, Rajpal teaches that SLUDGE (salivation, lacrimation, urination, diaphoresis, gastrointestinal motility, emesis) symptoms are caused by organophosphate poisoning, see page 144, first column first paragraph.
Therefore, the invention as a whole was prima facie obvious at the time it was invented.
RESPONSE TO ATTORNEY ARGUMENTS;
The Attorney response argues Rajpal in view of Rawas-Qalaji and Nibha do not provide any teaching or suggestion that high molecular weight atropine sulfate, is suitable to be administered as a rapid disintegrating sublingual tablet.
The Attorney response argues Rajpal teaches sublingual (SL) atropine sulfate injections but does not teach or suggest a SL tablet even though the use case discussed is field-based rapid administration, where a tablet would likely be preferred over an injection, i.e. reaching a therapeutic range and peak concentration of drug in blood earlier than 30 minutes and as close to IV range as possible, citing to Rajpal page 144, right hand column. The Attorney response argues that a person of skill would not have predicted these results and would have no expectation of success if they were to attempt to develop the claimed method.
In response, while Rajpal teaches an alternative solution of a sublingual injection to a sublingual tablet, the mere teaching of alternative does not equate to a teaching away. “[T]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). It is conceded that Rajpal teaches sublingual injection, however, the fact that Rajpal teaches an alternative sublingual route does not necessarily teach away from other alternative sublingual routes such as tablets, absent an explicit critique, discrediting or otherwise discouraging of the solution (sublingual tablets) claimed. Rajpal teaching of the sublingual alternative to sublingual tablets does not constitute a teaching away.
The Attorney response states that the formulations of Rawas-Qalaji rely on epinephrine, not comparable to atropine sulfate due its different chemical properties (low M.W. [183.20 M.W] and lipophilicity) that make it a good sublingual tablet candidate. The Attorney response argues in contrast, atropine sulfate is a large molecule i.e. high MW [694.83 M.W], and a person of skill would not refer to Rawas-Qalaji to prepare an atropine sulfate rapid disintegrating tablet, especially not expecting to achieve the high dissolution rates as per Fig 6 of the Application.
As detailed in the previous response, the Examiner notes that the physical characteristics cited from Nibha regarding molecular weight and lipophilicity are to be taken in context as general guidance and not absolutes to prevent the formulation of atropine sulphate into sublingual tablets. In summary from the Examiner’s response to Attorney in the final office action, the laundry list of drug compounds from Nibha is noted by the Examiner to reflect the diverse types of drug compounds in terms activity and physical properties that can be formulated into sublingual formulations. Despite the Attorney response that certain generalized guidelines from Nibha are rigidly applied to exclude a rationale to use atropine sulfate in sublingual formulations, Nibha notes many different drugs with differing physical properties can be used with SL formulations.
The Attorney response attempts to rebut the Examiner’s reliance upon Nibha to note it merely provides general information on sublingual drug delivery, but does not address the specific challenges of formulating high MW drugs like atropine sulfate, i.e. oxytocin SL is a tablet, film, liquid lozenge, etc. The Attorney response states without such guidance for a SL tablet, including an atropine SL, a person of skill would not have an expectation of success applying the information of Nibha to the claimed atropine SL tablet.
In response, taking the Attorney arguments at face value, that Nibha fails to teach high MW tablets of oxytocin and/or atropine sulfate, it is pointed out that Nibha does provide the advantages of sublingual tablets in general, and discusses high MW drugs as suitable for sublingual administration. See above advantages of SL tablets taught by Nibha as summarized at page 6, column 1, Section Advantages.3
The Attorney response states the rejection fails to fully consider the differences between administration formulations, and the influence of the molecular weight of atropine sulfate on its suitability for sublingual tablet administration. The Attorney response notes Exhibit A (Khaire) and Exhibit B (Zhang et al.) for the general premise that smaller molecules typically less than 500 Da are preferred as they easily penetrate the sublingual mucosa, pointing out that atropine sulfate has a MW of 694.83 (as per Khaire). The Attorney response notes Zhang et al. discusses 20 different drugs (including scopolamine, buprenorphine and nicotine), and that none of the drugs with MW over 500 Da were suitable for rapid-dissolving tablets. The response concludes a PHOSITA would refer to Zhang and Khaire and be discouraged from developing the claimed formulation.
In response, both Khaire and Zhang (Exhibits A and B) do provide general guidelines with regard to drug compounds greater than 500 Da and use of sublingual tablets, or not. However, it is noted that Zhang discloses a drug approaching 500 Da, Verapamil Section 3.1.3. (454.60 MW), in “a more recent study in healthy volunteers revealed that sublingual administration verapamil produced a significantly higher Cmax, a faster rate of absorption and greater bioavailability than oral administration.” See page 667, column 2.
Applicant concludes that its ex vivo model to test its atropine sulfate tablet for rapid disintegration, achieved dissolution rates similar to those in Rajpal’s injectable formulations. At this point, absent any further elaboration or discussion by the Applicant precludes a finding of unexpected results sufficient to overcome the prima facie case of obviousness.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 15-16, 18, 20, 30-35 and 37-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 12337063 in view of Rajpal et al. American Journal of Emergency Medicine (2010) 28, 143–150. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference patent claims an atropine sulfate tablet for sublingual administration and rapid disintegration (see claims 1-5) with the same filler, superdisintegrant, lubricant etc. in view of Rajpal that teaches use of atropine sulfate to treat exposure to organophosphates in a subject. See abstract.
Examined claims 15-16, 18, 20, 30-35 and 37-44 are directed to a method of treating organophosphate (OP) exposure (via pesticides, nerve agents etc.), with various properties of treating hypersalivation and a tablet sufficiently hard to pass a USP friability test, with an atropine sulfate tablet (rapid disintegration SL tablet, comprising from about 20 to about 95 w/w% of microcrystalline cellulose as the filler, from about 1 to about 15 w/w % of hydroxypropyl cellulose as the superdisintegrant, and from about 0.5 to about 3 w/w % of magnesium stearate as the lubricant).
As discussed reference patent claims 1-5 disclose the claimed atropine sulfate tablet, where Rajpal teaches atropine sulfate to treat OP exposure.
Regarding claims 20 and 37 and a cholinesterase reactivator, Rajpal teaches the co-administration of the cholinesterase re-activator, pralidoxime chloride, see page 144, first column, first full paragraph.
Conclusion
In summary, no claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 This application is a 371 of PCT/US15/53713 10/02/2015. PCT/US15/53713 has priority to US Provisional 62/058,722 filed 10/02/2014. This application has published as US20170246158A1.
2 Nibha and Pacholi “An Overview on: Sublingual Route for Systemic Drug Delivery,” Published April 2012. www.ijrpbsonline.com, Footnote 9 citing to in, Richman MD, Fox D, Shangraw RF. Preparation and stability of glyceryl trinitrate sublingual tablets prepared by direct compression. J Pharm Sci 1965; 54(3): 447‐451.
3 As recited in the obviousness rejection, Nibha 2012 discloses sublingual tablets advantages include ease of administration; convenience in administration of drug and accurate dosing as compared to liquid formulations; good mouth feel vs bitter pills; fast dissolution of medicament and absorption for rapid, onset of action; provides advantages of liquid formulations in the form of solid dosage form, see page 6, column 1, Section Advantages.