DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claims and Previous Objections/Rejections Status
Claims 1,4,5,7-13,15,18,19,21,36-38,41 and 49-52 are pending in the application. Claims 50-52 are newly added in the amendment filed 7/17/26.
Newly submitted claims 51 and 52 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: the original claims of a therapeutic topical composition comprise an active ingredient and an antibiotic did not include the “at least one additional agent” of claims 51 and 52.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 51 and 52 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a
rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claims 1,4,5,7-13,15,21,36-38,41,51 and 52 are withdrawn from consideration.
Response to Arguments
Applicant's arguments filed 7/17/26 have been fully considered but they are not persuasive.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 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, 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 negated by the manner in which the invention was made.
Claim 18,19,49 and 50 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Tizzano et al. (PNAS (2010) 107, 3210-3215) in view of Liggett et al. (US 2013/0131108A1) and Gulbransen et al. (J. Neurophysiol. 99: 2929-2937, 2008) and in further view of LeMahieu et al. (US 2008/0066739A1), Margolskee et al. (US 6,540,978B1), Sohi et al. (Drug Dev. Ind. Pharm. 2004, 30, 429-
448) and Kurtz et al. (US 5,232,735) as stated in the office action mailed 4/17/26 but modified to include newly added claim 50.
With regards to newly added claim 50,
The references of Tizzano et al. and Liggett et al. teach of denatonium compositions.
The references of Gulbransen et al. teaches that the classic bitter compound phenylthiocarbamide (PTC) elicits a large increase in [Ca2+].
The denatonium and PTC encompass the denatonium and PTC of the instant claims, have the same properties and are capable of the same functions, such as an ionic strength in the range of 150-200 mEq/L and can be formulated to be administered by lavage.
The recitation of “formulated to be administered by lavage” is a product-by-process limitation. Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process. In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed Cir. 1985). See MPEP 2113.
Applicant asserts that Tizzano et al., Liggett et al., Gulbransen et al., LeMahieu et al., Margolskee et al., Sohi et al. and Kurtz et al. alone or in combination do not teach or suggest a therapeutic topical composition for treatment of an infection of the upper respiratory tract comprising an active ingredient selected from denatonium, absinthin, phenylthiocarbamide (PTC), a homoserine lactone, and sodium thiocyanate (NaSCN), further comprising at least one antibiotic, and wherein the infection of the upper respiratory tract comprises acute or chronic rhinosinusitis.
The reference of Tizzano et al. was not explicitly used to teach acute or chronic rhinosinusitis.
The reference of Tizzano et al. was used to teach of a 10-20 mM denatonium composition that
activates the innate immune system to combat bacterial invasion in the upper respiratory tract. SCCs present in the upper respiratory tract respond to the presence of the bitter tastant denatonium via a PLC-mediated cascade to generate an increase in intracellular Ca2+.
The reference of Liggett et al. was used to teach that bitter tastant nasal inhalant compositions (p5, [0044]) (aerosol spray, nebulizer, vaporizer) comprising denatonium, quinine, etc. and one or more pharmaceutically acceptable carriers, such as saline, buffered saline, etc. that bind to bitter taste receptors, such as T2Rs and evoke an increase in [Ca2+].
At the time of the invention it would have been obvious to one of ordinary skill in the art to formulate a denatonium composition of Tizzano et al. in a pharmaceutically acceptable carrier as an nasal inhalant for the advantage of binding denatonium to T2R bitter taste receptors expressed on SCCs for increase in [Ca2+] and activation of the innate immune system to combat the bacterial invasion of the upper respiratory tract.
It would have been predictable to one of ordinary skill in the art that a nasally inhaled (aerosol spray, nebulizer, vaporizer) denatonium solution will be delivered to the upper respiratory tract prior to contacting the lower respiratory tract, initially bind to bitter taste receptors present in the upper respiratory tract and evoke an increase in Ca2+ to treat an upper respiratory tract infection, with a reasonable expectation of success as Liggett et al. teaches that bitter taste receptors are present in the anterior nasal cavity (p11, [0087]).
The denatonium encompasses the denatonium of the instant claims, has the same properties and is capable of the same functions, such as being a composition for treatment of an infection of the upper respiratory tract wherein the infection of the upper respiratory tract comprises acute or chronic rhinosinusitis.
Products of identical chemical composition can not have mutually exclusive properties. A chemical composition and its properties are inseparable. Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable and does not render the old composition patentably new to the discoverer. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977)
Applicant asserts that LeMahieu discloses antibiotics used in combination with drugs including bitter tastants such as propylthiouracil but does not teach therapeutic topical composition comprising a therapeutically effective amount of denatonium, absinthin, phenylthiocarbamide (PTC), a homoserine lactone, and sodium thiocyanate (NaSCN), further comprising at least one antibiotic. LeMahieu does not teach upper respiratory tract infections, let alone wherein the upper respiratory tract infection comprises acute or chronic rhinosinusitis.
The reference of LeMahieu was not used to teach of a therapeutic topical composition
comprising a therapeutically effective amount of denatonium, absinthin, phenylthiocarbamide (PTC), a
homoserine lactone, and sodium thiocyanate (NaSCN), further comprising at least one antibiotic or an
upper respiratory tract infection comprising acute or chronic rhinosinusitis.
The reference of LeMahieu was used to teach of the combination of inhalable bitter tastants with inhalable antibiotics for combination therapy.
The reference of Liggett et al. further teaches of combination therapy for the administration to a respiratory tract.
At the time of the invention it would have been obvious to one ordinarily skilled in the art to include an antibiotic in an inhalable bitter tastant pharmaceutical composition as LeMahieu et al. teaches of the combination of inhalable antibiotic and bitter tastant for the method of administering a drug to the respiratory system of a patient for the advantage of a combination therapy and Liggett et al. teaches of combination therapy for the administration to a respiratory tract.
It would have been predictable to one of to one of ordinary skill in the art that the nasally inhalable bitter tastant pharmaceutical composition comprising a inhalable antibiotic contacts the upper respiratory tract prior to contacting the lower respiratory tract wherein the bitter tastant (e.g.
denatonium) is available for binding to bitter taste receptors located in the upper respiratory tract.
Applicant asserts that Tizzano does not teach topical compositions or pharmaceutically acceptable carriers. Tizzano does not teach antibiotics.
The reference of Tizzano was not explicitly used to teach of a topical composition and was not used to teach antibiotics.
The reference of Tizzano was used to teach a 10-20 mM denatonium composition used
to active the innate immune system to combat the bacterial invasion in the upper respiratory tract. SCCs in the upper respiratory tract respond to the presence of the bitter tastant denatonium via a PLC-mediated cascade to generate an increase in intracellular Ca2+. Therefore, Tizzano et al. envisioned
administering a denatonium composition to the SCCs of the upper respiratory tract.
The reference of Liggett et al. was used to teach of a denatonium composition (aerosol spray,
nebulizer, vaporizer) comprising one or more pharmaceutically acceptable carriers, such as saline,
buffered saline, etc.
At the time of the invention it would have been obvious to one of ordinary skill in the art to formulate the denatonium composition of Tizzano et al. in a pharmaceutically acceptable carrier to yield a composition that can be inhaled nasally by a subject.
The reference of LeMahieu was used to teach of the combination of bitter tastants with inhalable antibiotics for combination therapy.
The reference of Liggett et al. further teaches of combination therapy for the administration to a respiratory tract.
At the time of the invention it would have been obvious to one ordinarily skilled in the art to include an antibiotic in an inhalable bitter tastant pharmaceutical composition as LeMahieu et al. teaches of the combination of inhalable antibiotic and bitter tastant for the method of administering a drug to the respiratory system of a patient for the advantage of a combination therapy and Liggett et al. teaches of combination therapy for the administration to a respiratory tract.
It would have been predictable to one of to one of ordinary skill in the art that the nasally inhalable bitter tastant pharmaceutical composition comprising a inhalable antibiotic contacts the upper respiratory tract prior to contacting the lower respiratory tract wherein the bitter tastant (e.g.
denatonium) is available for binding to bitter taste receptors in the upper respiratory tract.
Applicant asserts that Liggett does not teach upper respiratory tract infections, let alone wherein the upper respiratory tract infection comprises acute or chronic rhinosinusitis. Liggett does not teach routes of administration and the use of pharmaceutically acceptable carriers for treatment of infections of the upper respiratory tract and stimulating an innate microbial response in the upper respiratory tract. Ligget is instead directed to enhancing airway dilation and/or relieving bronchoconstriction to treat obstructive lung diseases such as asthma and COPD by administering bitter tastants that bind to bitter taste receptors expressed on the surface of airway smooth muscle cells to subjects in need thereof. Obstructive lung diseases and upper respiratory infections are distinct diseases with distinct pathologies. A skilled artisan will appreciate that airway smooth muscle cells are located in the walls of the bronchi and bronchioles which are part of the lower respiratory tract and not the upper respiratory tract. Ligget in fact defines “bitter tastants” as “an compound…. that binds to a bitter taste receptor present on the surface of an airway smooth muscle cell and, via such binding, relaxes the airway smooth muscle cell.”
The reference of Liggett et al. was not used to teach of upper respiratory tract infections comprising acute or chronic rhinosinusitis but was used to teach of a denatonium composition (aerosol spray, nebulizer, vaporizer) comprising one or more pharmaceutically acceptable carriers, such as saline, buffered saline, etc. used to bind to bitter taste receptors, such as T2Rs and evoke an increase in [Ca2+].
The reference of Tizzano was used to teach a 10-20 mM denatonium composition used
to active the innate immune system to combat the bacterial invasion in the upper respiratory tract. SCCs in the upper respiratory tract respond to the presence of the bitter tastant denatonium via a PLC-mediated cascade to generate an increase in intracellular Ca2+. Therefore, Tizzano et al. envisioned administering a denatonium composition to the SCCs of the upper respiratory tract.
At the time of the invention it would have been obvious to one of ordinary skill in the art to formulate a denatonium composition of Tizzano et al. in a pharmaceutically acceptable carrier as an inhalant for the advantage of binding denatonium to T2R bitter taste receptors expressed on SCCs for increase in [Ca2+] and the activation of the innate immune system to combat the bacterial invasion of the upper respiratory tract.
It would have been predictable to one of ordinary skill in the art that a nasally inhaled (aerosol
spray, nebulizer, vaporizer) denatonium solution will be delivered to the upper respiratory tract prior to contacting the lower respiratory tract, initially bind to bitter taste receptors present in the upper respiratory tract and evoke an increase in Ca2+ to treat an upper respiratory tract infection, with a reasonable expectation of success as Liggett et al. teaches that bitter taste receptors are present in the anterior nasal cavity (p11, [0087]).
The denatonium encompasses the denatonium of the instant claims, has the same properties and is capable of the same functions, such as being a composition for treatment of an infection of the upper respiratory tract wherein the infection of the upper respiratory tract comprises acute or chronic rhinosinusitis.
Products of identical chemical composition can not have mutually exclusive properties. A chemical composition and its properties are inseparable. Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable and does not render the old composition patentably new to the discoverer. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977)
Applicant asserts that Margolskee et al., Sohi et al. and Kurtz et al. do not teach upper respiratory tract infections, let alone wherein the upper respiratory tract infection comprises acute or chronic rhinosinusitis. They are entirely silent on compositions for treating an infection of the upper respiratory tract and stimulating an innate microbial response in the upper respiratory tract. The upper respiratory tract is a distinct section of the respiratory system which is subject to unique infections and consequently requires unique and distinct treatment compositions.
The references of Margolskee et al., Sohi et al. and Kurtz et al. were not used to teach of upper respiratory tract infection comprising acute or chronic rhinosinusitis or compositions for treating an infection of the upper respiratory tract and stimulating an innate microbial response in the upper respiratory tract.
The reference of Margolskee et al. was used to teach of a combination of bitter taste
inhibitors/inhibitor sweeteners and bitter compounds/tastants.
The reference of Sohi et al. was used to teach that lactisole is a bitterness inhibitors known in the taste masking of pharmaceuticals.
The reference of Kurtz et al. was used to teach that sweetness inhibitors are substantially
tasteless bitter taste inhibitors or blockers that can be added to pharmaceuticals.
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 18,19,49 and 50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1,2,4-6,9 and 10 of U.S. Patent No. 10,881,698 in view of Tizzano et al. (PNAS (2010) 107, 3210-3215) as stated in the office action mailed 4/17/26 but modified to include newly added claim 50.
Claims 18,19,49 and 50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 15 of copending Application No. 17/996,853 in view of LeMahieu et al. (US 2008/0066739A1) and Tizzano et al. (PNAS (2010) 107, 3210-3215) as stated in the office action mailed 4/17/26 but modified to include newly added claim 50.
With respect to claim 50, the bitter taste receptor agonists comprising denatonium, PTC,
homoserine lactone, NaSCN, quinine, etc. that encompasses the denatonium, PROP, PTC, homoserine lactone, NaSCN, quinine, etc. of the instant claims, have the same properties and are capable of the same function, such as an ionic strength in the range of 150-200 mEq/L and can be formulated to be administered by lavage.
Products of identical chemical composition can not have mutually exclusive properties. A chemical composition and its properties are inseparable. Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable and does not render the old composition patentably new to the discoverer. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).
The recitation of “formulated to be administered by lavage” is a product-by-process limitation. Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process. In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed Cir. 1985). See MPEP 2113.
Applicant respectfully requests that the double patenting rejections be held in abeyance until claims are deemed allowable in the instant application.
The rejections are maintained.
Conclusion
No claims are allowed at this time.
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 MELISSA JEAN PERREIRA whose telephone number is (571)272-1354. The examiner can normally be reached M9-3, T9-3, W9-3, Th9-2, F9-2.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached at 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MELISSA J PERREIRA/ Examiner, Art Unit 1618
/Michael G. Hartley/ Supervisory Patent Examiner, Art Unit 1618
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