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
Status of Claims
Claims 1-2,9-10,14-15,19 and 69 are pending. The claims are directed to Group 1 (elected without traverse) in the March 21 2025 reply. The species election of NK1R antagonist, L-733,0602
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and dry eye disease (DED) was also acknowledged. Upon search and further consideration the species election has been expanded to include the polypeptide Spantide and the NK1R antagonist, CP99994.
Information Disclosure Statement
The information disclosure statement (IDS) submitted 9-9-2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Interpretation
Claims 1 and 15 recite a composition comprising one or more neurokinin I receptor (NKIR) antagonists. . . wherein said NK1R antagonist comprises:
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While listing the various NK1R antagonists listed therein, with the alleged intent to limit the claims to the NK1R antagonists listed therein (see Attorney arguments pages 12-13 to overcome written description dated 8/18/2025), due to the use of the term comprises, the claims are broadly and reasonably interpreted to claim any NK1R antagonists beyond the specific compounds claimed and listed therein.
Response to Arguments
Applicant’s cancellation of claim 7, filed Aug 18 2025, with respect to the objection of claim 7 has been fully considered and are persuasive. The objection of claim 7 has been withdrawn.
Applicant’s arguments with respect to claim(s) 1, 3, 5, 7, 9, 14-16 and 18-19 rejected under 35 USC 112(a) for lack of written description, have been considered but are not applicable because of the amendment of claims 1 and 15 and cancellation of claims filed Aug 18 2025. See new rejection of claims for lack written description as detailed below.
Applicant’s remarks and cancellation of claim 7, filed Aug 18 2025, with respect to the rejection of claim 7 under 35 USC 112(b) have been fully considered and are persuasive. The rejection of claim 7 has been withdrawn.
Applicant's arguments filed Aug 18 2025 with regard to the rejection of claims 1, 3, 7, 10, 15, 16 and 18 as being anticipated by Taketani Abstract, have been fully considered. Due to the amendment of claims 1 and 15, a new novelty rejection has been issued, see detailed rejection of amended claims below and response to arguments.
Applicant's arguments filed Aug 18 2025 with regard to the rejection of claims 1, 3, 5, 7, 9-10, 14-16, 18 and 19 as being anticipated by WO 98/14193 A1 ("WO '193") , have been fully considered and are persuasive. The rejection of claims 1, 3, 5, 7, 9-10, 14-16, 18 and 19 has been withdrawn.
Applicant's arguments filed Aug 18 2025 with regard to the rejection of Claims 1-3, 5, 7, 9-10, 14-16 and 18-19 rejected under 35 U.S.C. 103 as being unpatentable over WO 98/14193 A1 (WO 193) in view of Langosch have been fully considered and are persuasive. The rejection of claims 1-3, 5, 7, 9-10, 14-16 and 18-19 has been withdrawn, however a new rejection has been issued over WO 193, in view of Stevenson and Langosch, see rejection of claims necessitated by amendment below.
Specification
The disclosure is objected to because of the following informalities: the specification makes multiple references to the NK1R antagonist, L-703,060. See for example page 26 bridging to page 27, where it in summary, referencing FIG. 16C (reproduced below) is a schematic representation showing the molecular structure of L-703,060, an analogue CP-96,345, said to have a benzylamino quinuclidine structure instead of a piperidine ring.
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The structure in FIG. 16C is not a clean, legible structure of L-706,060 as required. Further, Google and SciFinder searches for L-703,060’s chemical structure did not uncover any substance results.
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Appropriate correction, by providing a clear chemical structure, is required.
Claim Objections
Claim 2 is objected to because of the following informalities: it recites the NK1R antagonist compound, L-703,060. As detailed above, the specification does not provide a clear, legible chemical structure, and without such definition of structure from the specification, claim 2 is objected to for reciting L-703,060.
Appropriate correction, by providing a clear chemical structure, is required.
Claim Interpretation
Claims 1 and 15 recite a composition comprising one or more neurokinin I receptor (NK1R) antagonists. . . wherein said NK1R antagonist comprises:
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While listing the various NK1R antagonists listed therein, with the alleged intent to limit the claims to the NK1R antagonists listed therein (see Attorney arguments pages 12-13 to overcome written description dated 8/18/2025), due to the use of the term comprises, the claims are broadly and reasonably interpreted to claim any NK1R antagonists beyond the specific compounds claimed and listed therein.
New Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 9, 10, 14, 15, 19 and 69 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 and 15 recite administering to the claimed subject, a composition comprising one or more NK1R antagonists, wherein said NK1R antagonist comprises the various NK1R antagonists recited therein as detailed below, as detailed below.
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Claim 1 recites the limitation "one or more NK1R antagonists" in lines 2-3 while also reciting “said NK1R antagonist comprises” in line 6. “[O]ne or more” NK1R antagonists (plural) is not proper antecedent basis for “said” NK1R antagonist (singular).
There is insufficient antecedent basis for this limitation in the claim, because the open ended limitation of one or more NK1R antagonists opens the question said NK1R antagonist is claimed by antecedent basis.
Amendment of the claim to change “one or more” to “a”, OR, a later recitation of “the one or more” with reference to the NK1R antagonists will overcome the rejection by establishing proper antecedent basis. For example a first recitation of “a” NK1R antagonist followed by “said” NK1R antagonist, OR, a first recitation of “one or more” NK1R antagonists, followed by an amendment to “the one or more” NK1R antagonists.
A broad and reasonable interpretation under MPEP2112 is that the claim requires the presence of one NK1R antagonist form the recited list, or any analog thereof, where the recited item term “analogs” is not defined or otherwise limited by the instant specification.
With regard to the “analogs” issue, claims 1 and 15 fail to properly define the metes and bounds of the claimed method’s composition comprising NK1R antagonists, where said NK1R antagonists comprises those compounds recited therein, including CP99994 and L-733,060, the first two compounds listed. The use of comprises renders the claim indefinite as it unknown whether the list of recited NK1R antagonists of claims 1 and 15 is intended to limit the composition to these NK1R antagonists, or whether the list of recited NK1R antagonists claimed merely comprise those listed therein, and can further include more NK1R antagonists not listed. For purposes of examination, the claims are given the broader interpretation as discussed above so as to include any NK1R antagonist.
Dependent claims 9, 10, 14, 19 and 69 are similarly rejected for depending on indefinite claims 1 and 15 and failing to address the indefinite deficiencies of the rejected base claims.
New Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 9, 10, 14, 15, 19 and 69 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims lack adequate written description as the scope NK1R inhibiting compounds (of claim 1 and claims dependent) and scope of SP signaling block inducing agent (i.e., antagonist of claims 15, 16, 18 and 19) are broader than those described by the specification’s working examples.
As detailed in the claim interpretation section above, claims 1 and 15 are broadly and reasonably interpreted to include any NK1R antagonist, where the claims recite a composition comprising one or more neurokinin I receptor (NK1R) antagonists. . . wherein said NK1R antagonist comprises the list of compounds cited therein. While the claims specifically recite a list of compounds that it appears to intend the claims are to be limited to, the transition term “comprises” claims any NK1R antagonist beyond those listed therein.
The specification provides description for the claimed method, NK1R inhibitors/SP signaling blockade inducing agents such as those listed in claims 1 and 15. Amendment of claims 1 and 15 to delete the term “comprising” and replace it with a term (consisting of) to limit the NK1R antagonists listed therein will overcome this rejection.
Note that claim 1 does not list L-703,060 among the NK1R antagonists claimed. An amendment to limit claim 1 to a Markush group of NK1R antagonists listed therein will require either deletion of L-703,060 from claim 2, or claiming L-703,060 among the compounds of claim 1 so that claim 2 properly further limits proposed amended claim 1.
Claim Rejections - 35 USC § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 10 and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Taketani et al., "Abstract: Restoration of regulatory T cell function in dry eye disease by targeting substance P/neurokinin 1 receptor," Abstract, Presented at Proceedings of the 2019 AR VO Annual Meeting, Vancouver, Canada, April 28-May 2, 2019, 2 pages (Taketani Abstract). Taketani Abstract is NPL Ref. 8 on the Aug 24 2023 IDS.
As detailed above, amended claims 1 and 15 are broadly and reasonable interpreted to be directed to any NK1R antagonist, including the polypeptide Spantide.
Regarding claims 1 and 15 directed to the treatment of dry eye syndrome (aka, dry eye disorder (DED), a regulatory T-cell, Treg associated ocular disorder) with an NK1R inhibitor compound with the polypeptide Spantide, Taketani abstract teaches the administration of Spantide to Substance P/NK1R dry eye mouse models. See title (Restoration of regulatory T cell function in dry eye disease by targeting substance P [SP]/neurokinin 1 receptor [NK1R]) and abstract. Taketani abstract teaches that treatment of DED mouse models with Spantide restores the immunoregulatory function of Tregs. See abstract. While not explicitly reciting a composition in Taketani abstract, intraperitoneal administration of Spantide to a subject must inherently require a composition comprising Spantide.
Regarding claim 10 and at least once a day administration, Taketani abstract teaches Spantide was administered from one day before DED induction until day 14 intraperitoneally, where Spantide was administered at least once on one day of the study. See abstract.
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 the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 9, 10,14, 15, 19 and 69 are rejected under 35 U.S.C. under 35 U.S.C. 103 as being unpatentable over WO 98/14193 A1 (WO 193), in view of Stevenson et al. Dry eye disease: an immune-mediated ocular surface disorder. Arch Ophthalmol. 2012 Jan; 130(1):90-100.
WO 193 is cited on the IDS dated Aug 24 2023 as For. Ref. 2. Stevenson et al., is cited on the IDS dated May 25, 2023
As detailed above, amended claims 1 and 15 are broadly and reasonable interpreted to be directed to any NK1R antagonist, including the NK1R antagonist CP9994.
Regarding claims 1 and 15 directed to the treatment of dry eye disorder (DED), a regulatory T-cell, Treg associated ocular disorder), or symptom of DED thereof, with an NK1R inhibitor compound with a compound such as CP 99994, first compound listed in claim 1, WO 193 teaches a method for using a composition comprising said NK1R inhibitor compound (taught as a Substance P antagonist) for treating a subject in need, where (2S,3S)-3-(2-methoxybenzyl)amino-2-phenylpiperidine, aka CP 99994. See claims 1 and 2.
See page 2, lines14-20 disclosing the compound.
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aka CP 99994. See also Example 1 and claims 3-4 disclosing an ophthalmic composition comprising an SP antagonist CP 99994.
Regarding claim 1 and especially claim 15, WO 193 teaches that CP 99994, and therefore compositions comprising it, are useful for treating ocular pain associated with dry eye and conjunctivitis. See page 2, last line bridging to page 3, line 3. While listing other causes other than dry eye for ocular pain, the listing of dry eye and conjunctivitis by WO 193 in the limited group allows a PHOSITA a rationale to treat dry eye pain in a subject.
While the claims recite the limitation the ocular immunoinflammatory disorder requires an NK1R antagonist, such property of CP99994 is deemed to be necessarily present, whether expressly recited or not by the prior art.
Where WO 193 teaches treatment of dry eye pain, such as that caused by conjunctivitis, it does not teach treatment of dry eye disease (DED) specifically.
However, a person having ordinary skill in the art (PHOSITA) would have a reasonable expectation of success in arriving at the claimed invention to treat a subject suffering specifically from dry eye disease (DED). Stevenson teaches
Dry eye disease (DED), also known as keratoconjunctivitis sicca, is a
multifactorial disorder of the tears and ocular surface. Common symptoms of
DED include dryness, irritation, foreign body sensation, light sensitivity, and
itching. It is estimated that almost 5 million Americans 50 years and older have
DED, and millions more experience episodic symptoms of dry eye; of these,
approximately two-thirds are women. See page 90.
With regard to where the subject in need is suffering from a regulatory T cell (T reg) associated ocular disorder, such as dry eye disease/disorder (DED), per the Background section of the Specification, it is known that DED is characterized by chronic ocular surface inflammation. See page 1, lines 14-24. Accordingly, such chronic ocular surface inflammation requires the subject’s immune response “achieving immune quiescence by restoring or enhancing suppressive function of regulatory T cells (Tregs) in non-infectious immunoinflammatory disorders such as ocular redness, dry eye disease, and/or ocular pain, via blocking substance P (SP) signaling.” See Summary section of the specification, at page 1 line 29 bridging to page 2, line 3. A subject suffering from dry eye pain and dry eye disease as per WO 193 in view of Stevenson, would necessarily suffer from a Treg associated ocular disorder as claimed, as supported by WO 193 teaching that CP 99994 is a substance P antagonist.
Where WO 193 teaches the claimed NK1R antagonist CP 99994, for the treatment of dry eye and conjunctivitis and the associated pain, where common symptoms of dry eye disease (aka, DED or keratoconjunctivitis sicca), include dryness, irritation, etc., a PHOSITA would have a rationale to treat DED per se as detailed by WO 193 in view of Stevenson.
As required by claims 9 and 10, WO 193’s claims 1-4 disclose ocular administration (described as ophthalmic (topical) administration) of the composition and an ophthalmic composition per se. Further, page 4, lines 1-2 teach administration of the ophthalmic composition 1-4 times a day.
Regarding claim 14 and the requirement of a combination of a secondary therapy or secondary agent, WO 193 teaches its ophthalmic compositions comprising various ingredients such as the vehicles, mineral oil, liquid lanolin or white petrolatum, where such vehicles are known to treat a disorder such as dry eye, or alleviate pain and discomfort for painful or irritated eye conditions. See page 3, lines 20-22.
Claim 15 is directed to a method of reducing a symptom of non-infectious ocular immunoinflammatory disorder (DED) in a subject afflicted with a Treg-associated ocular disorder a composition comprising administering an NK1R receptor antagonist including CP99,9994. Claim 16 depends from claim 15 and recites the elected species DED to be treated. Claim 18 specifically teaches NK1R as the SP receptor.
Regarding claim 15, WO 193 teaches an ophthalmic composition and method of treating pain as a symptom of dry eye disorder, with an NK1R antagonist/ SP antagonist, CP99994, as per claims 1-4 and pages 2-3 reciting treatment of ocular pain caused by dry eye. See above.
As required by claim 19, WO 193 teaches topical (ophthalmic) administration with a composition comprising CP99994, see claims 1-4.
Regarding claim 69 and the limitation of a symptom of stinging and burning eye symptoms, WO 193 teaches treatment of ocular pain reasonably interpreted to include eye stinging and eye burning. See WO 193, claims 1-4 and pages 2-3 reciting treatment of ocular pain caused by dry eye.
Claims 1, 2, 9, 10, 14, 15, 19 and 69 are rejected under 35 U.S.C. 103 as being unpatentable over WO 98/14193 A1 (WO 193) in view of Stevenson et al. Dry eye disease: an immune-mediated ocular surface disorder. Arch Ophthalmol. 2012 Jan; 130(1):90-100 and Langosch et al. Effects of substance P and its antagonist L-733060 on long term potentiation in guinea pig hippocampal slices, Progress in Neuro-Psychopharmacology & Biological Psychiatry 29 (2005) 315 – 319. Stevenson et al., which is cited in the IDS dated May 25, 2023. Langosch is listed on the PTO-892 form.
As detailed above, WO 193 in view of Stevenson renders claims 1, 9, 10, 14, 15, 19 and 69 obvious, however they do not teach the particular species of claim 2, the NK1R antagonist L-733,060 as recited in claim 2. As detailed below, the teachings of Langosch render claim 2 and the species of L-733,060 obvious as detailed below.
As detailed above, amended claims 1 and 15 are broadly and reasonable interpreted to be directed to any NK1R antagonist, including the NK1R antagonists CP9994 and L-733,060.
Regarding claims 1 and 15 directed to the treatment of dry eye disorder (DED), a regulatory T-cell, Treg associated ocular disorder), or symptom of DED thereof, with an NK1R inhibitor compound with a compound such as CP 99994, first compound listed in claim 1, WO 193 teaches a method for using a composition comprising said NK1R inhibitor compound (taught as a Substance P antagonist) for treating a subject in need, where (2S,3S)-3-(2-methoxybenzyl)amino-2-phenylpiperidine, aka CP 99994. See claims 1 and 2.
See page 2, lines14-20 disclosing the compound.
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aka CP 99994. See also Example 1 and claims 3-4 disclosing an ophthalmic composition comprising an SP antagonist CP 99994.
Regarding claims 1 and especially claim 15, WO 193 teaches that CP 99994, and therefore compositions comprising it, are useful for treating ocular pain associated with dry eye and conjunctivitis. See page 2, last line bridging to page 3, line 3. While listing other causes other than dry eye for ocular pain, the listing of dry eye and conjunctivitis by WO 193 in the limited group allows a PHOSITA a rationale to treat dry eye pain in a subject.
While the claims recite the limitation the ocular immunoinflammatory disorder requires an NK1R antagonist, such property of CP99994 or L-733060 and all NK1R antagonists is deemed to be necessarily present, whether expressly recited or not by the prior art.
Where WO 193 teaches treatment of dry eye pain, such as that caused by conjunctivitis, it does not teach treatment of dry eye disease (DED) specifically.
To address this, Stevenson teaches
Dry eye disease (DED), also known as keratoconjunctivitis sicca, is a
multifactorial disorder of the tears and ocular surface. Common symptoms of
DED include dryness, irritation, foreign body sensation, light sensitivity, and
itching. It is estimated that almost 5 million Americans 50 years and older have
DED, and millions more experience episodic symptoms of dry eye; of these,
approximately two-thirds are women. See page 90.
With regard to where the subject in need is suffering from a regulatory T cell (T reg) associated ocular disorder, such as dry eye disease/disorder (DED), per the Background section of the Specification, it is known that DED is characterized by chronic ocular surface inflammation. See page 1, lines 14-24. Accordingly, such chronic ocular surface inflammation requires the subject’s immune response “achieving immune quiescence by restoring or enhancing suppressive function of regulatory T cells (Tregs) in non-infectious immunoinflammatory disorders such as ocular redness, dry eye disease, and/or ocular pain, via blocking substance P (SP) signaling.” See Summary section of the specification, at page 1 line 29 bridging to page 2, line 3. A subject suffering from dry eye pain and dry eye disease as per WO 193 in view of Stevenson, would necessarily suffer from a Treg associated ocular disorder as claimed, as supported by WO 193 teaching that CP 99994 is a substance P antagonist.
While WO 193 and Stevenson teaches the subject matter of claims 1 and 15 detailed above with regard to the species CP 99994, it does not teach the species subject matter of elected species L-733060,
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as a Substance P(SP)/ NK1R antagonist. Note that claim 2 recites the elected L-733060 compound as a species. To address the species of L-733060, Langosch teaches that elected L-733060 is an antagonist of substance P (SP), as well as neurokinin 1 receptor (NK1-R). See title and abstract. Langosch establishes the L-733060 as a SP/NK1-R antagonist where it notes that in guinea pig hippocampus models, 1 µM concentration of L-733060 suppressed the excitatory effects of 1µM substance P (SP). See abstract and page 317, column 12, bridging to page 318, column 1, Section Results.
WO 193 teaches that substance P (SP) antagonist type compounds, are known to treat the ocular inflammatory disorder, dry eye disease pain as claimed. Langosch teaches the NK1R antagonist, L-733060 is a SP antagonist compound.
A person having ordinary skill in the art (PHOSITA) would have a reasonable expectation of success in arriving at the claimed invention to treat a subject suffering specifically from dry eye disease (DED) with an NK1R antagonist, based off the teachings of WO 193 in view of Stevenson, where Langosch provides a reasonable expectation of success in arriving at the claimed invention with the particular elected species of SP antagonist/NK1R antagonist, L-733060 as detailed below.
A PHOSITA following the teachings of WO 193 and Stevenson to treat the elected species of disorder, dry eye disorder, with one SP antagonist, CP 99994, would have found the claimed method of treatment prima facie obvious as Langosch teaches a functional equivalent with L-733060 SP’s antagonist activity suppressing SP activity and also L-733060 NK1R antagonist activity as claimed.
The rationale to support the obviousness rejection is the simple substation of one known SP antagonist (CP 99994 as per WO 193 to treat dye disease in view of Stevenson) for another SP antagonist (L-733,060 as per Langosch), as WO 193, in view of Stevenson and Langosch teach their respective compounds are both SP antagonists and therefore substitutable, and where Langosch further teaches the NK1R antagonism of L-733060 as recited by the claims.
Regarding claim 2 and the limitation of L-7333060, Langosch teaches the NK1R antagonist and SP antagonist, L-7333060. See title and abstract.
As required by claims 9 and 10, WO 193’s claims 1-4 disclose ocular administration (described as ophthalmic (topical) administration) of the composition and an ophthalmic composition per se. Further, page 4, lines 1-2 teach administration of the ophthalmic composition 1-4 times a day. While WO 193 does not explicitly teach L-733060, as detailed above, a PHOSITA would have the rationale to simply substitute one SP antagonist for another as detailed above. Based on this, it would be prima facie obvious to administer an ophthalmic composition comprising L-733060 as taught by the combination of WO 193 and Langosch, so as to administer ophthalmically and up to 1-4 times a day as per WO 193.
Regarding claim 14 and the requirement of a combination of a secondary therapy or secondary agent, WO 193 teaches its ophthalmic compositions comprising various ingredients such as the vehicles, mineral oil, liquid lanolin or white petrolatum, where such vehicles are known to treat a disorder such as dry eye, or alleviate pain and discomfort for painful or irritated eye conditions. See page 3, lines 20-22.
Claim 15 is directed to a method of reducing a symptom of non-infectious ocular immunoinflammatory disorder (DED) in a subject afflicted with a Treg-associated ocular disorder a composition comprising a therapeutically effect amount of an SP signaling blockade-inducing agent.
Regarding claim 15, WO 193 and Stevenson teach an ophthalmic composition and method of treating pain as a symptom of dry eye disorder, with an NK1R antagonist/ SP antagonist, CP99994, as per claims 1-4 and pages 2-3 reciting treatment of ocular pain caused by dry eye. See above. While WO 193 does not explicitly teach L-733060, as detailed above, a PHOSITA would have the rationale to simply substitute one SP antagonist for another as detailed above. It would be prima facie obvious to administer an ophthalmic composition comprising L-733060 (as a substitute of CP 99994) as taught by the combination of WO 193 in view of Stevenson and Langosch, so as to administer ophthalmically acceptable compositions comprising L-733060 to treat pain as a symptom of dry eye disorder.
As required by claim 19, WO 193 teaches topical (ophthalmic)administration with a composition comprising CP99994, see above. While WO 193 does not explicitly teach L-733060, as detailed above, a PHOSITA would have the rationale to simply substitute one SP antagonist for another as detailed above. Based on this, it would be prima facie obvious to administer an ophthalmic composition comprising L-733060 (as a substitute of CP 99994) as taught by the combination of WO 193 and Langosch, so as to topically administer ophthalmically acceptable compositions comprising L-733060.
Regarding claim 69 and the limitation of a symptom of stinging and burning eye symptoms, WO 193 teaches treatment of ocular pain reasonably interpreted to include eye stinging and eye burning. See WO 193, claims 1-4 and pages 2-3 reciting treatment of ocular pain caused by dry eye.
RESPONSE TO ATTORNEY ARGUMENTS:
The Attorney response argues the rejection does not teach each and every limitation, accompanied by a motivation to combine the references in the manner suggested, where a PHOSITA would have a reasonable expectation of success.
The Attorney response states WO 193 fails to teach the limitations of the claimed invention, in particular treatment of DED, alone or in combination with Langosch.
The Attorney response argues Langosch does not teach or suggest can be used to treat any immunoinflammatory disorder or any eye-related disease.
In response, as detailed above, the treatment of DED has been taught where Stevenson teaches that DED (aka keratoconjunctivitis) is known to be associated with dryness, irritation etc. As detailed above, where WO 193 teaches the NK1R antagonist CP99994 for treating dry eye, a PHOSITA would have a rationale to combine its teachings of treating dry eye/conjunctivitis and associated irritation and pain with those teachings of Stevenson noting DED (aka keratoconjunctivitis) are associated with similar etiology such as conjunctivitis, eye irritation, etc.
In response to applicant's arguments against the references individually (the critique of the Langosch not teaching immunoinflammatory disorders or any eye-related disorder), one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
The deficiencies of Langosch brought up the Attorney are addressed by the combination of WO 193, Stevenson and Langosch as detailed above.
The Attorney response argues a PHOSITA would not have combined WO 193 and Langosch to arrive at the clamed methods. The Attorney response states a PHOSITA reading WO' 193 would not read it to treat TREG associated ocular disorder such as DED but merely is associated for treatment of pain.
The Attorney response states WO 193 have little in common other than to demonstrate Substance Preceptor antagonists as potential analgetic agents, where at best, WO 193 and Langosch would lead a PHOSITA to arrive at a method of treating ocular pain with L-733,060. The Attorney response argues but for impermissible hindsight, is a PHOSITA able to arrive at the claimed invention.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
As detailed above, the combination of WO 193 in view of Stevenson establishes the treatment of DED and associated symptoms with NK1R antagonists as detailed above, where Langosch teaches that elected L-733060 is an antagonist of substance P (SP), as well as neurokinin 1 receptor (NK1-R).
The prima facie case of obviousness is established solely from teachings of WO 193, Stevenson and Langosch, which was within the level of ordinary skill at the time the claimed invention (not knowledge gleaned from the disclosure), where reconstruction of the claimed invention to establish the prima face case.
Conclusion and Correspondence
In 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 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 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
1See Filing Receipt issued May 31 2022, reproduced below.
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2 CAS Number 148687-76-7
Chemical Name: (2S,3S)-3-[[3,5-bis(Trifluoromethyl)phenyl]methoxy]-2-phenylpiperidine hydrochloride