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
Response to Amendment
Status of the Claims
Receipt of Applicant’s response, filed 06 Mar 2026 has been entered.
Claims 1-14, 19, and 20 remain pending in the application.
Claims 1, 2, and 7 are amended.
Claims 15-18 are cancelled.
Claims 4, 5, and 11-14 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claims 1-3, 6-10, 19 and 20 are under consideration to the extent that the other active is tadalafil.
Rejections Withdrawn
Rejections Pursuant to 35 USC § 112
The rejections of claims pursuant to 35 U.S.C. 112(b) set forth in the Non-Final Office Action mailed 18 Feb 2025 are hereby withdrawn in light of applicants amendment of the claims.
Rejections Pursuant to 35 USC § 102
The rejection of claims pursuant to 35 U.S.C. 102(a)(1) set forth in the Non-Final Office Action mailed 18 Feb 2025 are hereby withdrawn in light of applicant’s amendment of the claims, and in favor of the new grounds of rejection set forth below.
Rejections Maintained
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.
The rejection below was made previously and is now made again and is updated to address the new claim amendments.
Claims 1-3, 6, 8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Dordunoo (WO 2022/026591, published 03 Feb 2022).
Dordunoo teaches pharmaceutical formulations suitable for sublingual administration containing a PDE5 inhibitor to treat male erectile dysfunction and/or comorbidities associated with erectile dysfunction (page 1 lines 8-14). Dordunoo teaches that exemplary embodiments include tadalafil as the PDE5 inhibitor (page 6 lines 12-13). Dordunoo teaches that the PDE5 inhibitor is present from about 0.5 mg to about 40 mg or from about 1% to about 40% by weight (page 13 lines 11-27), meeting the amount requirement for tadalafil in claim 3. Dordunoo teaches combining the PDE5 inhibitor with one or more second pharmaceutical agents useful for treating other types of disorders (page 17 lines 7-9). Dordunoo teaches combining therapeutic agents for the treatment of comorbid diseases associated with erectile disfunction such as diabetes, cardiovascular disorders and depression (page 3 lines 13-17). Dordunoo teaches oxytocin as another pharmaceutical agent in an exemplary amount of 0.02% by weight (page 7 lines 23-24), meeting the percent requirements of claims 1 and 3. Dordunoo teaches an example formulation in Table 16 comprising oxytocin. Based on the amounts displayed in the table the oxytocin is at approximately 0.07%, meeting the percent requirement of claim 2. Regarding the absence of optional actives in claim 2, Dordunoo teaches other suitable PDE5 inhibitors such as sildenafil (page 6 lines 7-8), which is not one of the other active compounds of claim 1. Thus, it is obvious to form a composition with oxytocin and a PDE5 inhibitor such as sildenafil in the absence of the optional active components of claim 1. Additionally, as noted in the 112(b) rejection above, the claim limitation of “in the absence of said optional active” is unclear as to what is required per the limitation and it may be interpreted that the claim merely requires that the combination of each of the optional actives is not present. Dordunoo does not require the combination of vardenafil, tadalafil and apomorphine and thus meets the limitation of claim 2.
Dordunoo teaches an example of a sublingual tablet that can be a liquisolid formulation wherein a liquid drug solution is converted into a dry, non-adherent free-flowing and readily compressible powder by blending with selected powder excipients, carriers and/or coating materials (page 4 line 31 – page 5 line 1), meeting the limitation of a loose powder amenable to tableting by compression as in claim 1. Dordunoo teaches excipients such as binders, lubricants and other tablet forming agents such as sodium stearyl fumarate and microcrystalline cellulose in appropriate amounts to form tablets that are stable (page 8 lines 27-29), rendering obvious the carrier of claim 1 and 6. Dordunoo teaches an example formulation with sodium stearyl fumarate at 1% and crospovidone at 5% (page 28 table 15), rendering obvious claims 8 and 10.
Dordunoo does not expressly teach selecting the amount of oxytocin with tadalafil in claim 3 or the absence of the optional actives of claim 2 or the specific amounts of carrier components of claims 8 and 10 with sufficient specificity to rise to the level of anticipation.
However, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention to have formed a sublingual composition as a powder with 0.02% or 0.07% oxytocin composition with 1-40% tadalafil (or other PDE5 inhibitor such as sildenafil) and 1% sodium stearyl fumarate and 5% crospovidone. One of ordinary skill in the art would have been motivated to do so as oxytocin and a PDE5 inhibitor such as tadalafil and sodium stearyl fumarate and crospovidone are taught by Dordunoo as suitable components for sublingual compositions in the amounts described above. One of ordinary skill in the art would have a reasonable expectation of successfully forming a powdered sublingual composition with these components since the modification of the prior art represents nothing more than the predictable use of prior art elements according to their established functions.
Accordingly, the instant claims are rendered prima facie obvious over the teachings of Dordunoo.
Response to Arguments
Applicant's arguments filed 06 Mar 2026 have been fully considered but they are not persuasive. Applicant states that Dordunoo is directed to liquid phase formulations with aprotic solvents and mesoporous dicalcium phosphate and mesoporous silica and that one would not be motivated to abandon this liquid solvent approach to use the carrier materials and manufacturing approach of instant invention (pages 9-10 of remarks). The examiner does not find this persuasive. It is not necessary for one to abandon any of the features necessary to the invention of Dordunoo in order to render obvious to instant claims. Dordunoo may prepare the composition differently from the applicants but the claims are directed to a composition and not to a method of forming the composition. Additionally, the claims are open to additional ingredients not recited and that may be different from what the applicant used due to the open ended “comprising” language of the claims. While the compositions of Dordunoo are liquisolid formulations, the description of this formulation taught by Dordunoo renders obvious the instant claims. Dordunoo teaches a sublingual tablet that can be a liquisolid formulation wherein a liquid drug solution is converted into a dry, non-adherent free-flowing and readily compressible powder by blending with selected powder excipients, carriers and/or coating materials (page 4 line 31 – page 5 line 1). This meets the limitations of a loose powder amendable to tableting by compression in a tablet press (claim 1) and the form of a sublingual tablet (claims 19 and 20). Further, Dordunoo teaches excipients such as binders, lubricants and other tablet forming agents such as sodium stearyl fumarate and microcrystalline cellulose in appropriate amounts to form tablets that are stable (page 8 lines 27-29), thus rendering obvious the carrier component as required per claims 1 and 6. Thus, it is not necessary to abandon approach of Dordunoo to include the specific carrier components as the components are taught by Dordunoo as suitable for the compositions. The further addition of components and method steps alternative from the applicants desired form of the invention do not negate the obviousness from the teachings of Dordunoo as the claims are broadly directed to a composition with open ended language.
Claims 7 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Dordunoo (WO 2022/026591, published 03 Feb 2022) as applied to claims 1-3, 6, 8 and 10 above, and in view of Schaible et al. (US 2010/0285164, published 11 Nov 2010) as evidenced by Cabot (Untreated fumed silica CAB-O-SIL® M-5).
The teachings of Dordunoo are described supra.
Dordunoo does not teach untreated fumed silica, colloidal silicon dioxide, mannitol and fructose as in claims 7 and 9. These deficiencies are made up for in the teachings of Schaible.
Schaible teaches a mono-particulate directly compressible orally disintegrating tablet and an excipient composition comprising a cellulose coprocessed with a silicon dioxide, a polyol/sugar blend and a disintegrant ([0001]). Schaible teaches a preferred cellulosic material is microcrystalline cellulose ([0024]) and the polyol may be mannitol ([0027]) and the sugar may be fructose ([0028]). Schaible teaches a metal oxide compressibility augmenting agent ([0020]) that is a fumed or colloidal metal oxide such as silicon dioxide ([0026]) and is present from about 1-10% ([0025]). Schaible teaches an example silicon dioxide of Cabosil® M-5-P ([0129], Table 2). As evidenced by Cabot, Cabosil® M-5 is an untreated fumed silica (page 1). Schaible teaches the inclusion of 0.1 to 20% of a lubricant such as sodium stearyl fumarate ([0032]) and a disintegrant such as crospovidione ([0061]). Schaible teaches that soild dosage forms of the invention disintegrate in accordance with USP29 disintegration testing of substantial disintegration within 3 minute or less and in a preferred embodiment of 30 seconds or less ([0052]). Schaible teaches that the dosage formulation provide acceptable mouth feel upon disintegration and ability to mask unpleasant taste from the active agent ([0053], [0054]). Schaible teaches that the agglomerated excipient particles of the invention provide superior flow characteristics which allows for faster processing, and the particles have superior compaction characteristics and content uniformity when tableted ([0124-0126]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have formed the sublingual tablet compositions of Dordunoo with excipients of Cabosil® M-5-P (untreated fumed silica) or colloidal silicon dioxide from 1-10%, sodium stearyl fumarate, microcrystalline cellulose, mannitol, fructose and crospovidone. Excipients of sodium stearyl fumarate, microcrystalline cellulose and crospovidone are known as suitable for the sublingual tablet formulations, as taught by Dordunoo. 1-10% Cabosil® M-5-P (untreated fumed silica), colloidal silicon dioxide, mannitol and fructose are also known from Schaible to be excipient materials suitable for forming disintegrating tablets. Schaible additionally teaches sodium stearyl fumarate, microcrystalline cellulose and crospovidone, further indicating the obviousness of combining with the excipients taught by Dordunoo. It would be obvious to include the excipients stated above as they are known to provide benefits such as suitable disintegration, mouth feel and taste and improved processing and one would have a reasonable expectation of success in using the stated excipients as they are known to be suitable for disintegrating tablets, as taught by Schaible.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references.
Response to Arguments
Applicant's arguments filed 06 Mar 2026 have been fully considered but they are not persuasive. Applicant states that substituting Schaibles dry powder excipients into Dordunoo would render Dordunoo inoperable for its intended purpose as the mesoporous carrier of Dordunoo would be replaced by non-porous material (page 10 of remarks). This is not persuasive. The examiner notes that the rejection is not based on replacing the mesoporous carrier of Dordunoo but is instead based on the obviousness of including such excipient components in the composition of Dordunoo. Cabosil® M-5-P (untreated fumed silica), colloidal silicon dioxide, sodium stearyl fumarate, microcrystalline cellulose, mannitol, fructose and crospovidone are excipients known to be suitable for orally disintegrating tablets and their inclusion merely represents using known prior art elements according to their known purpose as excipients. It would not be necessary to remove the mesoporous material taught by Dordunoo and thus the applicants argument is not persuasive.
The rejection below was made previously and is now made again with the additional rejection of claim 19 as the claim is now being examined due to the applicant’s amendment.
Claims 19 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Dordunoo (WO 2022/026591, published 03 Feb 2022) in view of Schaible et al. (US 2010/0285164, published 11 Nov 2010) as evidenced by Cabot (Untreated fumed silica CAB-O-SIL® M-5) as applied to claims 1-3, and 6-10 above, and further in view of Moberg (US 2017/0232059, published 17 Aug 2017) as evidenced by the instant specification.
The teachings of Dordunoo and Schaible are described supra.
Dordunoo additionally teaches an example of a 250 mg compressed tablet (page 28 lines 3-5).
Dordunoo and Schaible do not teach 2.5 mg of oxytocin as in claim 20. This deficiency is made up for in the teachings of Moberg.
Moberg teaches a pharmaceutical composition comprising oxytocin for treatment of a disorder responsive to modulation of the endogenous oxytocin production (abstract). Moberg teaches the disorder includes depression and disturbances of cardiovascular function ([0011]). Moberg teaches sublingual administration ([0010]). Moberg teaches the oxytocin may be administered in a dose of about 10-10,000 IU or about 1,000 -6,000 IU, when administered sublingually ([0013], [0059]). As evidenced by the instant specification, 1 IU of oxytocin is equivalent to 1.68 μg of the pure peptide (page 8 line 1). Thus, 1,000-6,000 IU oxytocin is equivalent to 1,680 μg – 10,080 μg or 1.68mg-10.08mg.
Therefore, it would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have formulated a sublingual tablet with 10-10,000IU (1.68mg-10.08mg) oxytocin and 0.5mg-40 mg tadalafil. Sublingual tablets comprising oxytocin and 0.5mg-40mg tadalafil are obvious from Dordunoo. The amount of oxytocin for administration is variable, for example from 10-10,000IU (1.68mg-10.08mg), as taught by Moberg. One would have a reasonable expectation of success in formulating the tablet with oxytoxin in this range as it is known to be suitable for administration and Moberg additionally teaches sublingual administration. Further, the additional component such as oxytocin in the composition of Dordunoo is known to be used for treating conditions related to erectile dysfunction, such as depression and cardiovascular disorders and oxytocin is known to be associated with treating depression and disturbances of cardiovascular function, as taught by Moberg, providing further expectation of success in using the range as taught by Moberg in the tablets of Dordunoo.
Regarding the amount of 260.5 mg (claim 19) and 260.0mg (claim 20) of a mixture of fumed untreated silica, sodium stearyl fumarate, microcrystalline cellulose, colloidal silicon dioxide, mannitol, fructose, and crospovidone, the examiner notes that the combination of the excipient type components and their variability in amounts is obvious from the teachings of Dordunoo and Schaible, as described in the rejection above. As noted, Dordunoo teaches a tablet of 250 mg which is similar to the tablet and the amount of claims 19 and 20. As the excipient components are known and their amounts are variable as well as the tadalafil and oxytocin amounts are variable, as described above, the total amount of excipient of in the final tablet would simply be a result of routine experimentation in determining the optimal amounts of each component for delivery to the patient. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Tablets are known in the general range of 250mg, as taught by Dordunoo and the total amount of excipients being 260.5 mg and 260.0 mg would be a result of varying the excipients in the combination to achieve the optimal tablet properties as desired.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references.
Response to Arguments
Applicant's arguments filed 06 Mar 2026 have been fully considered but they are not persuasive. Applicant argues that Moberg’s oxytocin dosages are disclosed in the context of standalone oxytocin therapy and that Moberg does not disclose or contemplate combining oxytocin at the dosage with tadalafil in a dry powder sublingual tablet and does not teach PDE5 inhibitors, erectile dysfunction treatment or the specific carrier excipients of claim 20 (page 10 of remarks). This is not persuasive as Moberg is not relied upon to teach these other features as they are known from Dordunoo. Even though Moberg does not teach the specific components and use noted by the applicant, Moberg does teach the administration of oxytocin in the context of sublingual administration and the amount taught by Moberg provides a reasonable starting range for administration of oxytocin. Further, Dordunoo teaches administering additional drugs known to be used for treating conditions related to erectile dysfunction, such as depression and cardiovascular disorders (page 3 lines 11-22, page 12 lines 3-5) and oxytocin is known to be associated with treating depression and disturbances of cardiovascular function, as taught by Moberg, providing further connection with the compositions of Dordunoo and a reasonable expectation of success in using the range as taught by Moberg in the tablets of Dordunoo.
Applicant argues that Dodunoo’s liquisolid system requires co-dissolving the actives in a common aprotic liquid phase before adsorption onto the mesoporous carrier and that the aprotic solvents used to solubilize tadalafil are poor solvents for oxytocin. Applicant argues that the use of “consisting essentially of” with specific amounts of oxytocin, tadalafil and 360.0 mg of a defined dry powder carrier mixtures in claim 20 addresses the problems of solubility (page 10 of remarks). This is not persuasive as the claims are directed to a composition and it is not necessary that the composition be formed in the same manner as the applicant, such as without aprotic solvents. Further, it is noted that the claims are still open to additional components not recited with the “consisting exxentially of” language. The phrase “consists essentially of” limits the scope of a claim to the specified materials or steps "and those that do not materially affect the basic and novel characteristic(s)" of the claimed invention. In re Herz, 537 F.2d 549, 551-52, 190 USPQ 461, 463 (CCPA 1976) (emphasis in original). "A ‘consisting essentially of’ claim occupies a middle ground between closed claims that are written in a ‘consisting of’ format and fully open claims that are drafted in a ‘comprising’ format." PPG Industries v. Guardian Industries, 156 F.3d 1351, 1354, 48 USPQ2d 1351, 1353-54 (Fed. Cir. 1998). See also Atlas Powder v. E.I. duPont de Nemours & Co., 750 F.2d 1569, 224 USPQ 409 (Fed. Cir. 1984); In re Janakirama-Rao, 317 F.2d 951, 137 USPQ 893 (CCPA 1963); Water Technologies Corp. vs. Calco, Ltd., 850 F.2d 660, 7 USPQ2d 1097 (Fed. Cir. 1988). For the purposes of searching for and applying prior art under 35 U.S.C. 102 and 103, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, "consisting essentially of" will be construed as equivalent to "comprising." See, e.g., PPG, 156 F.3d at 1355, 48 USPQ2d at 1355. In the instant case the applicant has not established the solvent components of Dordunoo are incompatible and in light of the teachings of Dordunoo regarding the combination of oxytocin and tadalafil (e.g. pages 28-29 Example 3) and the formation of a free flowing powder (page 28 lines 10-15), the expectation is that the components are suitable for forming powder for sublingual tablets.
New Grounds of Rejection
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 6 and 8-10 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 6 and 8-10 recite that the “carrier comprises” which is open ended language, whereas claim 1, from which claims 6 and 8 depend, recite that the “carrier consists essentially of” which occupies a middle ground between closed claims that are written in a ‘consisting of’ format and fully open claims that are drafted in a ‘comprising’ format. Thus, claim 1 is narrower in relation to the carrier components than claims 6 and 8-10 and claims 6 and 8-10 broaden the limitations of claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
No claims are allowed.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EDWIN C MITCHELL whose telephone number is (571)272-7007. The examiner can normally be reached Mon-Fri 8:00-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, David Blanchard can be reached on (571)272-0827. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/E.C.M./Examiner, Art Unit 1619
/ANNA R FALKOWITZ/Primary Examiner, Art Unit 1600
Prosecution Insights