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 .
Priority
The instant application is a 371 National Stage Entry of PCT/US2023/011146 filed on January 19, 2023 which claims benefit to domestic provisional application No. 63/301,657 filed on January 21, 2022.
Status of Claims
Acknowledgement is made of original (1-3, 5, 8-11), amended (4, 6-7), and new (12) claims filed on July 18, 2024. Claims 1-12 are pending in instant application.
Information Disclosure Statement
The information disclosure statement filed on December 19, 2024 has been considered.
Specification
The disclosure is objected to because of the following informalities:
The specification states that three rabbits were used in a study to test four different compositions (see instant spec. at p. 69 and at Figure 1). It is unclear if there was a typo and Applicant meant four.
Appropriate correction is required.
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 6-9, 11-12, rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for increasing pupil diameter in vivo, does not reasonably provide enablement for treating or preventing a disease or condition where muscarinic acetylcholine receptor is implicated. 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.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the nature of the invention,
2- the breadth of the claims,
3- the state of the prior art,
4- the predictability of the art,
5- the amount of direction or guidance provided
6- the presence or absence of working examples,
7- the quantity of experimentation necessary, and
8- the relative skill of those in the art.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Undue experimentation is required by one skilled in the art to determine enablement of the instant disclosure as claimed due to the following:
The nature of the invention (1) and the breadth of the claims (2)
The nature of the invention and breadth of claim(s) is the treatment or prevention of a disease or condition where muscarinic acetylcholine receptor is implicated broadly (claims 6, 11, 12) or those diseases specifically listed in claims 7-9.
The instant specification defines treatment as:
1) inhibiting the disease; for example, inhibiting a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., arresting further development of the pathology and/or symptomatology), or 2) ameliorating the disease; for example, ameliorating a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., reversing the pathology and/or symptomatology). (see instant spec. at p. 32)
The instant specification defines “prevention” as:
decreasing the risk of occurrence of the disease, condition or disorder in a subject or group of subjects (e.g., a subject or group of subjects predisposed to or susceptible to the disease, condition or disorder). In some embodiments, preventing a disease, condition or disorder refers to decreasing the possibility of acquiring the disease, condition or disorder and/or its associated symptoms. In some embodiments, preventing a disease, condition or disorder refers to completely or almost completely stopping the disease, condition or disorder from occurring. (see instant spec. at p. 32)
The specification does not define “implicated”.
Furthermore, since subjects include animals and individuals (see instant spec. at p. 31 lines 30-32), and prevention includes prophylaxis for susceptible populations, the broadest reasonable interpretation includes a patient population of anyone.
The state (3) and predictability (4) of the art
MPEP § 2164.05(a) states if a publication demonstrates that those of ordinary skill in the art would not find that a particular invention was not enabled years after the filing date, the publication would be evidence that the claimed invention was not possible at the time of filing.
In regards to treating muscarinic acetylcholine receptor implicated diseases and unpredictability, Scarr et. al.1 teaches the effect of a particular treatment for a particular central nervous system disease depends on the muscarinic receptor targeted, e.g. M1-M5 (see Scarr at p. 376 right col. ¶3). Scarr cautions it is uncertain if animal models will translate to humans, and adverse side effects have included cerebrovascular vasodilation (see id).
In regards to unpredictability of atropine derivatives and therapeutic benefit, MacMillan et. al.2 teaches structurally similar compounds (atropine derivatives) as sweat gland inhibitors with a range of efficacy (see MacMillan at p. 363 right col. ¶2 and pp. 366-368 Table II, 0 being no sweat inhibition, 4 being excellent inhibition). MacMillan notes, “there has long been the desire to inhibit locally hyperhidrosis with topically applied anticholinergies without notable success to the present time.” (emphasis added, see MacMillan at p. 363 left col. ¶1). MacMillan thus informs artisans atropine derivates have unpredictability in treating hyperhidrosis.
WO 2016172712 A2 to Baker et. al.3 teaches ophthalmic compositions comprising atropine and atropine salts (see Baker at pp. 76-80) for treating focus deprivation myopia in guinea pigs (see Baker at p. 103 Example 17).
Further, regarding claims 6, 11-12, the methods include diseases and conditions not yet discovered and not yet discovered to be muscarinic acetylcholine receptor-implicated. It would certainly require undue experimentation to discover the enabled embodiments encompassed by claim 6-9, 11-12.
The prior art provides enablement for treating hyperhidrosis with specific atropine ester derivatives, or myopia with atropine sulfate.
The amount of direction or guidance provided (5) and the presence or absence of working examples (6)
The specification provides the following embodiments:
In Vivo Pupil Study: the specification discussed a pupil diameter study in rabbits comprising administering atropine sulfate, atropine oleate, or atropine linoleate. The Examiner notes only one of the species tested fall within the claimed genus of Formula I (atropine linoleate).
Atropine Sulfate
Atropine Oleate
Atropine Linoleate
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The specification provides enablement for increasing pupil diameter in vivo with atropine linoelate.
Nowhere in the specification is it explained how such any other condition encompassed by claims 6, 11, 12 are to be prevented through the administration of the claimed compounds. Also, it is not explained in the art or applicant’s disclosure how the following utilities are achieved by the methods of claims 7-9:
causing cycloplegic refraction in the eye of the subject, causing mydriasis in the eye of the subject, relieving an eye floater symptom, a patching therapy for children with amblyopia or lazy eye, reducing salivation and bronchial secretions, treating/preventing painful ciliary muscle spasm in the eye, treating/preventing myopia progression, treating/preventing a heart condition, hyperhidrosis, or treating/preventing poisoning.
Therefore, the full scope of treatment in the methods of claims 6-9, 11-12 are not enabled.
The quantity of experimentation necessary (7) and the relative skill of those in the art (8)
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. Because of the unknown predictability in the art (as discussed above) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that compounds of Formula I could be used as treatments for any disease encompassed by or specifically listed in claims 6-9, 11-12.
Brenner v. Manson states "[A] patent is not a hunting license. It is not a reward for a search but a compensation for its successful conclusion and 'patent 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" (Brenner v. Manson 383 U.S. 519, 536, 148 USPQ 689, 696 (1966), cited in Genentech Inc. vs. Nova Nordisk 42 USPQ 2d 1001, Fed. Circuit 1997).
As noted above, little experimentation provided is drawn to treatment, prevention, and prophylaxis of diseases listed in claim 6-9. A review of the state of the art fails to reveal that atropine derivatives are useful as therapeutic treatment as claimed (e.g. a heart condition, poisoning, reducing salivation). Determining if compounds of Formula I would be therapeutic for any particular disease state would require careful analysis and replicability of a composition comprising a compound of Formula I, formulation into a suitable dosage form, assay testing to correlate clinical efficacy, identifying receptor targets, identifying off-targets, subjecting to animal trials, and subjecting to clinical trials.
All this is undue experimentation given the limited guidance and direction provided by Applicants.
Conclusion
Accordingly, the inventions of claims 6-9, 11-12 do not comply with the enablement requirement of 35 U.S.C 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success.
Suggested Amendment
Absent unexpected results commensurate in scope with the claims, the Examiner suggests cancelling the method claims, or amending to a method of increasing pupil diameter.
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 3, 7, 9 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.
Claim 3 recites species with triple bonds, but the line angle drawings depict angled not linear bonds. It is unclear if it’s the typographical error is intended to indicate a double bond with an angle, or a linear triple bond. See examples below:
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Claim 7 recites the limitation "the eye floater symptoms". There is insufficient antecedent basis for this limitation in the claim (e.g. no eye floater symptoms previously mentioned). The Examiner recommends amending to omit “the” and incorporate “an”.
Claim 9 recites “A method for causing a condition selected from” but then goes on to list “for relieving an eye floater symptom” and “for treating or preventing…a myopia progression”. The claim reads as causing conditions, but then additionally recites what appear to be other methods which are not consistent with the causing preamble (e.g. a method for causing for preventing). It is assumed Applicant intends to indicate multiple methods in one claim. The Examiner recommends amending the claim to read as follows for clarity of claim interpretation:
Claim 9. A method:
i) for causing a condition selected from: cycloplegic refraction and mydriasis in the eye of the subject,
ii) for relieving an eye floater symptom in a subject,
iii) for patching therapy for children with amblyopia or lazy eye, or
iv) for treating or preventing a condition selected from: painful ciliary muscle spasm in the eye and a myopia progression,
the method of comprising…
However, see also 112(a) Issues above.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-3 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by STN.
STN4 teaches the following compounds which anticipate instant Formula I as described below.
CAS# 857812-09-0
Instant Formula I
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CAS# 857812-09-0 reads on instant Formula I when n is 0, R1 is aryl specifically methyl substituted with a carboxy, R3 is alkyl specifically methyl.
CAS# 103350-86-3
Instant Formula I
Instant Claim 3 Species
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CAS# 103350-86-3 reads on instant Formula I when n is 0, R1 is C7-34 alkyl specifically C13 alkyl, R3 is alkyl specifically methyl. CAS# 103350-86-3 corresponds to a claimed species (see instant claim 3 p. 9 last species), compound 6, “atropine myristate” (see instant spec. at p. 61).
CAS# 755690-18-7
Instant Formula I
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CAS# 755690-18-7 read on instant Formula I when n is 0, R1 is aryl specifically phenyl, and R3 is alkyl specifically isopropyl.
CAS# 756412-20-1
Instant Formula I
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CAS# 756412-20-1 reads on instant Formula I when n is 0, R1 is aryl specifically phenyl, and R3 is alkyl specifically methyl.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2021/019350 A1 to Kandula et. al.5
Regarding claims 1-3 and a compound of Formula I, Kandula teaches a species of a structurally similar genus to instant Formula I shown below (see Kandula at p. 19 and claim 6).
Kandula Claim 6
Formula VI
Kandula Species
Instant Formula I
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Regarding claim 4 and a composition, Kandula also teaches compositions comprising the disclosed compounds and a pharmaceutical carrier (see Kandula at claim 3).
The prior art differs from the instant claims as follows: While Kandula’s species shares an atropine core and an R1 heteroalkyl-substituted alkyl chain substituent with instant Formula I, instant Formula I requires the R1 alkyl length at minimum be a C7 alkyl.
However,
Regarding claims 1-2, this is not a patentably distinct difference because it amounts to homologous repetitive changes of -(CH2)-.
Regarding claim 3, Kandula teaches acceptable alternatives for Kandula Formula IV R1/R2 substituents (see Kandula claim 6) that read on instantly claimed species. For example, R1 may be null, and R2 may be as described below:
Kandula Claim 6 Formula IV
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Kandula Claim 6 R2 Substituent Option
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Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding claims 1-2, per MPEP § 2144.09(I)-(II), “[a] prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities” because “[c]ompounds which are…homologs…are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties” (see, e.g., MPEP § 2144.09(I)-(II)), and the Court has stated that “[i]f a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” KSR, 127 S.Ct. at 1740. In addition, per MPEP § 2144.08(II)(A)(4)(c), the closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. An artisan would thus have a reasonable expectation of success in synthesizing and formulating a homolog of Kandula’s species with a longer alkyl chain.
Regarding claim 3, per MPEP § 2143(I)(B), a prima facie case of obviousness exists for simple substitution of one known element for another to obtain predictable results. It would have been obvious to an artisan to substitute one known substituent in the art for another because the prior art teaches both are suitable alternate structures for the modifiable substituent indicated in the taught genus (as taught by Kandula).
Furthermore, it is well-within the ordinary skill in art to make a homolog of a known compound. Furthermore, it is well-within the ordinary skill in art to incorporate one known suitable substituent in lieu of another.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claim(s) 5 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Kandula as applied to claims 1-4 above and in further view of Dutesca et. al.6
Recall Kandula teaches compositions comprising disclosed compounds and a carrier (see Kandula at claim 3). Kandula teaches methods for the treatment of anal and rectal disorders (see Kandula at Title). Kandula also indicates that compositions comprising the disclosed compounds can be formulated for intraocular delivery (see Kandula at p. 22 ¶[0039]), and the active ingredient may be presented in the composition for localized use ocularly (see Kandula at p. 25 ¶[0051]).
The prior art differs from the instant claims as follows: While Kandula teaches compositions that may be formulated for intraocular delivery, Kandula does not specify a semifluorinated alkane carrier.
However,
Dutesca teaches semifluorinated alkanes are useful carriers for ophthalmic solutions and capable of dissolving lipophilic drugs (see Dutesca at Abstract).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Per MPEP § 2144.07, a prima facie case of obviousness exists for the selection of a known material based on its suitability for its intended use. Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945). It would have been obvious to an artisan to formulate a prior art composition comprising a lipid for ocular delivery (as taught by Kandula) with a semifluorinated alkane carrier (as taught by Dutesca), because the prior art teaches such a carrier is suitable for ophthalmic use and compatible with lipophilic drugs.
Furthermore, it is well-within the ordinary skill in art to select an ocular-compatible carrier for use in a composition intended for ocular delivery.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Conclusion
The specification is objected to.
Claims 6 is objected to.
Claims 1-12 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SOPHIA J REILLY whose telephone number is (703)756-5669. The examiner can normally be reached 9:00 am - 5:00 pm EST M-F.
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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.
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/S.R./Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Scarr, E. "Muscarinic Receptors: Their Roles in Disorders of the Central Nervous System and Potential as Therapeutic Targets" CNS Neurosci Ther. 2011 Feb 26;18(5):369–379. DOI: 10.1111/j.1755-5949.2011.00249.x. Hereinafter Scarr.
2 MacMillan et. al. "The Antiperspirant Action of Topically Applied Anticholinergics" Journal of Investigative Dermatology 1964, 43, 5, 363-377 DOI: 10.1038/jid.1964.167. Hereinafter MacMillan.
3 Published October 27, 2016. Hereinafter Baker.
4 STN is collectively referring to the following STN database entries:CAS 857812-09-0 CAS Registry File Accessed June 14, 2026 from STN, entered into STN August 1, 2005.
CAS 103350-86-3 CAS Registry File Accessed June 14, 2026 from STN, entered into STN July 26, 1986
CAS 755690-18-7 CAS Registry File Accessed June 14, 2026 from STN, entered into STN October 1, 2004.
CAS 756412-20-1 CAS Registry File Accessed June 14, 2026 from STN, entered into STN October 3, 2004.
5 Cite No. 4 in the IDS filed 12/19/24. Hereinafter Kandula.
6 Cite No. 6 in the IDS filed 12/19/24. Hereinafter Dutesca.
Prosecution Insights