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
Claims 1-5 filed on 05/12/2023 are acknowledged. No preliminary amendment was filed.
Priority
This application is a National Stage Application of PCT/MX2021/050074, filed on 11/11/2021 and claims foreign priority to MX/A/2020/012116 filed on 11/12/2020.
Information Disclosure Statement
The information disclosure statement (IDS) dated 05/12/2023 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609, except where noted. Accordingly, the IDS document has been placed in the application file and the information therein has been considered as to the merits.
Claim Objections
Claim 3 is objected to because of the following informalities: the semicolon located on line 3 after “0.5%” should be a comma. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-5 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.
Regarding claim 1 the term “preferably” located in each section i-iv and vi, renders the claim indefinite because it is unclear whether the limitations after said term(s) are part of the claimed invention. See MPEP § 2173.05(d). Claim 8 is rejected for being dependent from a rejected base claim. Claims 2-5 are rejected for being dependent on a rejected claim base.
Claim 1 recites a composition with a list of ingredients i-vii. The claim does not contain a conjunctional phrase such as “and” or “or” making it unclear which components must be included in the composition. For the purposes of applying prior art, the examiner will interpret claim 1 with the phrase “and” added to the end of claim 1 section vi to indicate that all components, i-vii, must be present in the composition.
Claim 2 recites the phrase “chlorhidrate” in the last line of the claim. It is unclear what “chlorhidrate” is and the specification does not further define the term. When searching the term “chlorhidrate” on Microsoft Edge Google search engine, chloral hydrate was the top reference which is a hypnotic sedative (https://www.bing.com/search?q=chlorhydrate&qs=n&form=QBRE&sp=-1&ghc=1&lq=0&pq=chlorhydrate&sc=12-12&sk=&cvid=B663966E36B7447698EB456B6DD6295A, accessed 09/04/2025, see PTO-892). When searching the term “chlorhidrate” on Chrome Google search engine, the top reference was for chlorhydrate which is the French spelling for hydrochloride (https://www.google.com/search?q=chlorhidrate&rlz=1C1GCEA_enUS1111US1111&oq=chlorhidrate&gs_lcrp=EgZjaHJvbWUqBggAEEUYOzIGCAAQRRg7MgkIARAAGAoYgAQyCQgCEAAYChiABDIJCAMQABgKGIAEMgkIBBAAGAoYgAQyCQgFEAAYChiABDIJCAYQABgKGIAEMgkIBxAAGAoYgAQyCQgIEAAYChiABDIJCAkQABgKGIAE0gEIMjU3NWowajGoAgCwAgA&sourceid=chrome&ie=UTF-8, accessed 09/04/2025, see PTO-892). Therefore, there is no clear indication of how to interpret the term “chlorhidrate”. For the purposes of applying prior art, the examiner will interpret the phrase “chlorhidrate” to be hydrochloride.
Claim 5 recites the phrase “for use in addition, in eliminating…” but does not clarify what it is in addition to. For the purposes of applying prior art, the examiner will interpret the phrase “for use in addition to, in eliminating” as “for use in addition to the use of claim 1, in eliminating”.
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 1-5 are rejected under 35 U.S.C. 112(a), because the specification, while being enabling for treating symptoms of presbyopia by administering an ophthalmic composition, it does not reasonably provide enablement for preventing symptoms of presbyopia. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
With respect to the claimed method, attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
All of the Wands factors have been considered and those most relevant to the cited claims are discussed below.
Nature of the invention: The invention is drawn to an ophthalmic composition for use in the prevention and treatment of the symptoms of presbyopia.
Relative skill of those in the art: The relevant art is pharmaceutical formulations, which is a mature art where practitioners receive specialized training and earn advanced degrees during the course of their study. There is a voluminous amount of published material describing research, best practices and practical application of compositions and techniques to the medical field. The relative skill of those in the art is high.
Breadth of claims: The claims are broad with respect to the concept of prevention. The full scope of the instant claims covers the entire definition of treatment and prevention as well any adverse effects from epidermolysis bullosa. The full scope of the claims encompasses the entire definition of tertiary prevention, which covers reducing the occurrence of or eliminating a symptom or condition. The term “prevention” is assumed to take on the customary meaning known to those skilled in the art. Specifically, “prevention” is defined according to the Institute for International Medical Education (Wojtczak, 2002) as: the goals within the field of medicine to promote health, to preserve health, to restore health when it is impaired, and to minimize suffering and distress. Customarily prevention is sub-classified as primary (the protection of health by personal and community wide effects), secondary (the measures available to individuals and populations for the early detection and prompt and effective intervention to correct departures from good health) and tertiary (the measures available to reduce or eliminate long-term impairments and disabilities, minimize suffering caused by existing departures from good health, and to promote the patient's adjustment to irremediable conditions). Tertiary prevention is most relevant as used in the context of the instant invention. Thus, the intent of the method, as interpreted by a skilled practitioner of the medical or pharmaceutical arts, would include that which reduces the occurrence of, or eliminates, a disease or condition caused by or associated with symptoms of presbyopia to an individual.
Amount of guidance/Existence of working examples:
The instant specification provides a clinical trial (instant specification pages 15-18) wherein subjects were administered the synergistic composition comprising pilocarpine, bromonidine, oxymetazoline/sodium hyaluronate, bromfenac and/or at least one vasoconstrictor. The results showed that pain in the synergistic composition administered subjects was reported to be 0 and two subjects treated with pilocarpine or brimonidine alone had reported pain (instant specification page 18). One subject treated with the synergistic composition did experience hyperemia (instant specification page 18). While the results support that the synergistic combination do reduce or inhibit the symptoms of presbyopia, the results do not support that the synergistic combination is effective at preventing the symptoms of presbyopia with the full scope of the claim.
State of the prior art/Predictability or unpredictability of the art:
Tsuneyoshi et al. (Scientific Reports, published 07/28/2017, see PTO-892) is drawn to the study of suppressing presbyopia progression with prenoxine eye drops (title). Tsuneyoshi teaches that there are various methods that can correct presbyopia and that there are supplements or warming devices that can relieve presbyopic symptoms (abstract). Presbyopic eyes is attributed to hardening of the lens with age (page 1). Tsuneyoshi showed that application of pirenoxine eye drops significantly suppressed hardening of the lens suggesting that pirenoxine eye drops might prevent progression of presbyopia. While the study supports that eye drop medications may be used to reduce or inhibit the symptoms of presbyopia, the results do not support that the eye drops could prevent the symptoms of presbyopia.
Quantity of experimentation: Prevention is difficult to determine due to the inability to control who will contract the condition and which symptoms they will experience. There is no disclosure or suggestion in the art or the specification on how to determine prevention. One of ordinary skill in the art would have to conduct a myriad number of experiments comprising trial and error administration of the claimed compositions to both healthy individuals and individuals with presbyopia to determine if the claimed compositions can be used in the fully claimed scope prevent all symptoms of presbyopia. Genetech, 108 F.3d at 1366, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Therefore, in view of the Wands factors as discussed above, e.g., the breadth of the claims, the amount of guidance provided, the state/unpredictability of the art and the lack of working examples, one of skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of the claims, with no assurance of success.
Claims 1-5 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 claims contain 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.
Claim 1 is drawn to a pharmaceutical composition comprising of a synergistic combination of: one or more cholinergic agonist agents, one or more alpha 1-adrenergic agonist agents, one or more glycosaminoglycan agents, one or more non-steroidal anti-inflammatory agents, and one or more vasoconstrictor agents. The instant disclosure, however, does not describe a representative number of species of the claimed genus performing the claimed function, nor does the disclosure identify a structure-function relationship that could be used to predictably identify which of the claimed agents could be used in combination with what other agents in order to arrive at a composition that is capable of performing the claimed functions.
The instant specification (page 17) discloses a clinical trial wherein patients were administered a synergistic ophthalmic composition comprising pilocarpine, brimonidine, oxymetazoline/sodium hyaluronate, bromfenac and/or at least one vasoconstrictor in a non-dominant eye and where also administered either pilocarpine or brimonidine in the dominant eye. Table 1 (instant specification page 17) compares the visual acuity (Jaeger scale) before administration (baseline), the synergistic mixture, pilocarpine alone, or brimonidine alone. The results suggest that there is a statistical difference between the synergistic mixture and baseline, but when comparing the synergistic mixture with either pilocarpine alone or brimonidine alone, there is no statistical difference to suggest a synergistic effect.
Further, only one example each of the one or more cholinergic agonist agents, one or more alpha 1-adrenergic agonist agents, one or more glycosaminoglycan agents, one or more non-steroidal anti-inflammatory agents, and one or more vasoconstrictor agents was tested with no additional agents from each genus tested to suggest that a synergistic result would results from any combination of the genus listed in claim 1 i-vi Tables 1-3 are cited in the instant specification (instant specification pages 17-18) to support the synergistic claim of the composition for claim 1, however, the data does not support the claim that there is a statistical difference between the synergistic composition and the pilocarpine or brimonidine alone. Thus, the instant disclosure does not provide a structure-function relationship which would allow a skilled artisan to recognize which compositions would result in the claimed synergy.
Furthermore, the state of the art prior to the effective filing date of the claimed invention demonstrates that synergy is unpredictable. Renna et al. (Eye and Vision, published 03/23/2017, see PTO-892) discusses several ophthalmic eye drops compounds solutions that have been described in peer-reviewed papers or presented in ophthalmological tabloids and congresses. Each topical treatment deals with drug combinations aimed to modify one or more factors involved in the accommodative process and have been proposed to be instilled either monocularly or binocularly. It remains unclear how much each drug in the final combined form is involved in the achievement of the outcome and contributes to it leading to a lack of a completely well understood mechanism (abstract).
For the purposes of applying prior art, the examiner will interpret the phrase “the synergistic combination” as the result of the five specific components in the specification: comprising pilocarpine, brimonidine, oxymetazoline, sodium hyaluronate, and bromfenac.
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.
Claims 1-5 are rejected under 35 U.S.C. 103 as being unpatentable Ostrow et al. (WO 2019/104191 A1, published 05/31/2019, see PTO-892) as evidenced by RxMed.com (accessed 08/27/2025, see PTO-892) and as evidenced by RxList.com (accessed 08/27/2025, see PTO-892).
Ostrow is drawn to ophthalmic compositions for treatment of an ophthalmic disorder or condition (abstract). Ostrow teaches that the composition may comprise a combination of ophthalmic agents including pilocarpine, oxymetazoline, bromfenac, phenylephrine, tetrahydrozoline and naphazoline (paragraph 0090). Ostrow teaches that the ophthalmic agent is present in the formulation at a concentration of from about 0.001 wt% to about 20 wt% (paragraph 0105). Ostrow teaches that sodium chloride may be used as an osmolarity adjusting agent (paragraph 0020) and in the exemplified compositions, uses 0.9% NaCl (paragraph 0544). Ostrow further exemplified the use of NaCl with a final concentration in the range of 0.5-2 wt% in the formulations in Tables 1-3. Ostrow teaches that pilocarpine may be IsoptoCarpine (paragraph 0232). As evidenced by RxMed.com, IsoptoCarpine is pilocarpine hydrochloride (page 1). Ostrow teaches that oxymetazoline may be OcuClear (paragraph 0228). As evidenced by RxMed.com, OcuClear is oxymetazoline hydrochloride (page 2). Ostrow teaches that that brimonidine may be Alphagan (paragraph 0232). As evidenced by RxMed.com, Aphagan is brimonidine tartrate (page 3). Ostrow teaches that bromfenac may be Bromday (paragraph 0226). As evidenced by RxList.com, Bromday is a bromfenac sodium (page 2). Additionally, oxymetazoline hydrochloride may act as both the alpha 1-adrenergic agonist agent and a vasoconstrictor agent as required by instant claim 1. Ostrow teaches that the composition may compromise a pharmaceutically acceptable carrier (0109) and that the pharmaceutically acceptable carrier may comprise at least one viscosity-enhancing agent such as hyaluronic acid (paragraph 0110) or sodium hyaluronate (paragraph 0450). Ostrow teaches that the compositions may contain from about 1% to about 10% of a viscosity enhancing agent such as the hyaluronic acid (paragraph 0409).
It would have been prima facie obvious before the effective filing date of the claimed invention to select pilocarpine hydrochloride, oxymetazolone hydrochloride, bromindine tartrate, the sodium salt of hyaluronic acid (hyaluronate), and bromfenac sodium for an ophthalmic composition as taught by Ostrow to arrive at the claimed invention. It would have been prima facie obvious for a person of ordinary skill in the art to select pilocarpine hydrochloride, oxymetazolone hydrochloride, bromindine tartrate, the sodium salt of hyaluronic acid (hyaluronate), and bromfenac sodium for an ophthalmic composition because Ostrow teaches an ophthalmic composition that comprises a combination of these ophthalmic agents. One of ordinary skill in the art would have a reasonable expectation of success because Ostrow teaches that they are ophthalmic agents that may be used in combination.
It would have been prima facie obvious before the effective filing date of the claimed invention to optimize the concentrations of pilocarpine, bromindine, oxymetazoline and hyaluronic acid within the range disclosed by Ostrow to arrive at the claimed invention. It would have been prima facie obvious for a person of ordinary skill in the art to optimize those concentrations and amounts of the opthalmic agents because Ostrow teaches that the ophthalmic agents may be used from 0.001 wt% to about 20% for the ophthalmic agents and 1 to 10% for the hyaluronic acid. Regarding the masses of oxymetazoline and hyaluronic acid in instant claim 3, one of ordinary skill in the art would understand that the mass range of 0.5 mg to 1 mg for oxymetazoline and 0.1 mg to 2.5 mg for hyaluronic acid could be achieved with the range of 0.001 wt% to 20% wt percent for oxymetazoline and the 1% to 10% for the hyaluronic acid depending on the volume. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). (MPEP § 2144.05(I)) Moreover, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[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). (MPEP § 2144.05(II)) “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003).
It would have been prima facie obvious before the effective filing date of the claimed invention to select a saline solution for the ophthalmic composition comprising pilocarpine and brimonidine as taught by Ostrow to arrive at the claimed invention. It would have been prima facie obvious for a person of ordinary skill in the art to select a saline solution to dilute the composition because Ostrow teaches that sodium chloride may be used as an osmolarity adjusting agent. One of ordinary skill in the art would have a reasonable expectation of success because Ostrow exemplifies an ophthalmic composition comprising 0.9% sodium chloride.
It is noted that the prior art does not teach that the composition can be used in the manner instantly claimed, for use in the prevention, control and treatment of the symptoms of presbyopia and to improve near vision ability and increase the depth of focus in the patient’s eyes or for use in eliminating the side elects of pilocarpine such as eye redness, headache and dryness of the eye. However, the cited recitations are considered an “intended use” of the claimed composition. The “intended use” of the claimed composition does not patentably distinguish the composition, per se, since such disclosed use is inherent in the reference composition. In order to be limiting, the intended use must create a structural difference between the claimed composition and the prior art composition. In the instant case, the intended use does not create a structural difference, thus the intended use is not limiting.
Conclusion
No claims allowed.
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/SAMANTHA LYNN SCHACHERMEYER/Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693