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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11/14/2025 has been entered.
Claims 1, 3-19, 26-36, 42-57, 59, 62-78 are pending.
Claims 42-45, 47, 48, 50-54, 56, 57, 59 are withdrawn from further consideration as non-elected specie. Election was made without traverse in the reply filed on 3/29/2023.
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.
Claim(s) 1, 3-19, 26-36, 46, 49, 55, 58, 62-78 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 10,806,709 (‘709) in view of US2017/0290776 (‘776) and WO2018/089570 (‘570).
‘709 teaches a method of treating anaphylaxis by administering anti-anaphylactic agents, including dipivefrin, intranasally (see the abstract, col. 9, line 20 for example). ‘709 teaches the particle size of the active as 20-50µm (see col. 16, lines 3-16). ‘709 teaches penetration or permeation enhancers being included to facilitate the absorption of the anti-anaphylactic agent in the amount of 1-30% (see col. 10, line 52 bridging col. 12, line 13). The dosage of the epinephrine in the instant invention is 0.05mg to 10mg (see claim 9). ‘709 teaches the volume intended to be administered as 100µl (see col. 26, lines 30-34). The examiner notes that the ratio between the actives and the permeation enhancing agent would meet the limitations of claims 2-7.
‘709 does not expressly teach the permeation enhancer as the extract of a clove plant. ‘709 does not expressly teach the herein claimed compound. ‘709 does not expressly teach the concentration of the permeation enhancer in the matrix. ‘709 does not expressly teach the herein claimed pharmacokinetic properties of the dipivefrin composition (e.g., Cmax, Tmax, the conversion time).
‘570 teaches the herein claimed epinephrine prodrug as suitable for use to treat anaphylaxis (see the abstract, also Fig. 2, and claim 1 for example).
‘776 teaches mucosal permeation systems for delivering an adrenergic-receptor modulators such as epinephrine (see for example claims and 19). ‘776 teaches a permeation enhancer as clove oil from clove leaf, bud, and/or stem (see Fig. 11 and example 1 for example). ‘776 teaches 3% of clove oil (see for example [0178]). ‘776 teaches the matrix comprising a water soluble polymer (see for example claim 21). ‘776 also teaches the pharmaceutical dosage form includes film (see claim 23).
It would have been obvious to one of ordinary skill in the art at the time of filing to employ the epinephrine prodrug recited in the claim in the method of treating anaphylaxis. It would have been obvious to one of ordinary skill in the art at the time of filing to incorporate the extract of clove plant as permeation enhancer and a matrix into the anti-anaphylactic dipivefrin composition. It would have been obvious to one of ordinary skill in the art to adjust the Cmax and Tmax of the dipivefrin composition.
One of ordinary skill in the art would have been motivated to employ the epinephrine prodrug recited in the claim in the method of treating anaphylaxis because the prodrugs of epinephrine taught in ‘570 including the one recited in the claims are well-known in the art to be useful in treating anaphylaxis. Therefore, employing any one of them would be reasonably expected to be effective.
One of ordinary skill in the art would have been motivated to incorporate the extract of clove plant as permeation enhancer and a matrix into the anti-anaphylactic dipivefrin composition. Since the penetration/permeation enhancers are known to be suitable and compatible with adrenergic modulator such as epinephrine for transmucosal administration, incorporating the extract of clove plant such as clove oil and the matrix of water-soluble polymer would be reasonably expected to impart beneficial effect for the dipivefrin composition. The examiner notes that the penetration enhancers is taught to be 3% in amount and the anti-anaphylactic agents to be 1-30% in amount. Accordingly, ratio between the penetration enhancer/ anti-anaphylactic agents (i.e., dipifevrin/epinephrine) meets the limitation recited in claim 1.
One of ordinary skill in the art would have been motivated to adjust the Cmax and Tmax of the dipivefrin composition. By adjusting the amount of the matrix would be reasonably expected to control the rate of the release and thereby the Cmax and Tmax. Therefore, the optimization of result effect parameters (e.g, amount of the excipients that affect the Cmax and Tmax) is obvious as being within the skill of the artisan. The optimization of known effective amounts of known active agents to be administered, is considered well in the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art. It has been held that it is within the skill in the art to select optimal parameters, such as amounts of ingredients, in a composition in order to achieve a beneficial effect. See In re Boesch, 205 USPQ 215 (CCPA 1980). It is also noted that “[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).
In addition, the herein claimed pharmacological and pharmacokinetic properties such as how fast the conversion from prodrug to active or whether the prodrug activate or not activate certain receptors is considered as an intrinsic property of the prodrug.
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.
Claims 1, 3-19, 26-36, 46, 49, 55, 58, 62-78 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16, 18, 21, 22, 24-60 of copending Application No. 17/576,923 (‘923) in view of ‘776.
‘923 teaches a method of treating allergic reaction using epinephrine and its prodrug (see claims 1 and 38 for example). ‘923 teaches the Cmax and Tmax properties of the administration of the epinephrine/prodrug composition (see claims 59-60).
‘923 does not expressly teach the permeation enhancer as the extract of a clove plant. ‘923 does not expressly teach the concentration of the permeation enhancer in the matrix. ‘923 does not expressly teach the herein claimed pharmacokinetic properties of the dipivefrin composition (e.g., Cmax, Tmax, the conversion time).
‘776 teaches mucosal permeation systems for delivering an adrenergic-receptor modulators such as epinephrine (see for example claims and 19). ‘776 teaches a permeation enhancer as clove oil from clove leaf, bud, and/or stem (see Fig. 11 and example 1 for example). ‘776 teaches 3% of clove oil (see for example [0178]). ‘776 teaches the matrix comprising a water soluble polymer (see for example claim 21). ‘776 also teaches the pharmaceutical dosage form includes film (see claim 23).
It would have been obvious to one of ordinary skill in the art at the time of filing to incorporate the extract of clove plant as permeation enhancer and a matrix into the anti-anaphylactic dipivefrin composition. It would have been obvious to one of ordinary skill in the art to adjust the Cmax and Tmax of the dipivefrin composition.
One of ordinary skill in the art would have been motivated to incorporate the extract of clove plant as permeation enhancer and a matrix into the anti-allergic dipivefrin composition. Since the penetration/permeation enhancers are known to be suitable and compatible with adrenergic modulator such as epinephrine for transmucosal administration, incorporating the extract of clove plant such as clove oil and the matrix of water-soluble polymer would be reasonably expected to impart beneficial effect for the dipivefrin composition.
One of ordinary skill in the art would have been motivated to adjust the Cmax and Tmax of the dipivefrin composition. By adjusting the amount of the matrix would be reasonably expected to control the rate of the release and thereby the Cmax and Tmax. Therefore, the optimization of result effect parameters (e.g, amount of the excipients that affect the Cmax and Tmax) is obvious as being within the skill of the artisan. The optimization of known effective amounts of known active agents to be administered, is considered well in the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art. It has been held that it is within the skill in the art to select optimal parameters, such as amounts of ingredients, in a composition in order to achieve a beneficial effect. See In re Boesch, 205 USPQ 215 (CCPA 1980). It is also noted that “[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). In the instant case, the adjustment of penetration enhancer amount would produce the desired serum concentration of the active agent and thereby treating the allergic condition.
In addition, the herein claimed pharmacological and pharmacokinetic properties such as how fast the conversion from prodrug to active or whether the prodrug activate or not activate certain receptors is considered as an intrinsic property of the prodrug.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1, 3-19, 26-36, 46, 49, 55, 58, 62-78 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicant's arguments filed 11/14/2025 averring the cited prior art’s failure to teach the herein claimed permeation enhancers, the herein claimed prodrug of epinephrine, have been fully considered but they are not persuasive. The examiner notes that prodrug as claimed have been fully considered but they are not persuasive. The examiner notes that ‘570 clearly teaches the anti-anaphylactic agents epinephrine derivative include the compound as claimed. Employing the prodrug compound as claimed in the nasal composition would be reasonably expected to be effective in treating anaphylaxis.
Applicant’s remarks with regard to the provisional double patenting rejection are acknowledged. Accordingly, the rejection is maintained.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAN MING R HUI whose telephone number is (571)272-0626. The examiner can normally be reached Mon - Fri 9:30-5:30.
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, Kortney Klinkel can be reached at 571-270-5239. 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.
/SAN MING R HUI/Primary Examiner, Art Unit 1627