-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 .
Applicant’s response dated March 2, 2026 is acknowledged.
Priority
This application is a 371 of PCT/US2020/041837 filed on 07/13/2020, and claims benefit
in provisional application 62/873, 121 filed on 07/11/2019.
Claim Status
Claims 1-40 are pending. Claims 25-40 remain withdrawn. Claims 41-92 were canceled.
Claims 1, 10, 25, and 33 were amended. Claims 1-24 are examined.
Maintained Claim Rejections-35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C.
102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the
statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a
new ground of rejection if the prior art relied upon, and the rationale supporting the rejection,
would be the same under either status.
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.
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 1-21, 23, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over
Ambati (WO 2017/155580 Al, published September 14, 2017) and Ostrow (CA 2 953 363
Published December 30, 2015).
The claims are drawn to a method of treating or preventing progression of myopia,
comprising administering a therapeutically effective amount of an ophthalmic composition to an
eye of a subject during a treatment period, said ophthalmic composition comprising: a corneal
cross-linking agent and a secondary therapeutic agent present in amounts sufficient to treat
myopic progression; wherein the secondary therapeutic agent is selected from the groups
consisting of atropine, among others, and a pharmaceutically acceptable carrier.
The teachings of Ambati are related to an ophthalmic composition or dosage form that
can include a therapeutically effective amount of a cross-linking agent and a pharmaceutically
acceptable carrier. The composition or dosage form can be used to treat an ophthalmic condition
by administering a therapeutically effective amount of the composition to an eye of a subject
during a treatment period (Abstract). For example, keratoconus (KCN) is a progressive disorder
associated with structural changes in corneal collagen organization that can lead to corneal
thinning and ruptures in Bowman's layer and/or Descemet's membrane. Typically, the disease
manifests in the second decade of life when the cornea assumes a more conical shape, which
leads to irregular astigmatism, progressive myopia, corneal thinning and subsequently poor
visual acuity (page l lines 14-19). Treating can be to reduce, ameliorate or eliminate symptoms
associated with a condition present in a subject, or can be prophylactic, (i.e. to prevent or reduce
the occurrence of the symptoms in a subject). Such prophylactic treatment can also be referred to
as prevention of the condition (page 4 lines 27-30).
In one example, an ophthalmic composition or dosage form is described herein. The
ophthalmic composition or dosage form can include an amount of a cross-linking agent, such as
a copper-containing agent, that is sufficient to increase lysyl oxidase activity in an eye of a
subject or otherwise increase cross-linking in the cornea of the subject. The composition or
dosage form can further include a pharmaceutically acceptable carrier. In some examples, the
dosage form can be an ophthalmic composition formulated as a topical eye drop and carried in a
container adapted to dispense the composition in a drop-wise manner at a drop volume of from
about 5 ul to about 50 ul. In another embodiment, a method is described for using such a
composition or dosage form. The method can include administering a therapeutically effective
amount of a composition or dosage form, as described herein, during a treatment period
(paragraph bridging pages 6-7). The compositions, dosage forms, and methods can be used to
treat a variety of ophthalmic indications. For example, a variety of ophthalmic conditions can
cause corneal thinning, biomechanical weakness of the cornea, and other corneal complications.
Such conditions can include corneal ulcers, peripheral ulcerative keratitis, corneal melts, pellucid
marginal degeneration, Terrien's marginal degeneration, neurotrophic disease of the cornea,
corneal ectasia (such as after refractive surgery), keratoconus, the like, or combinations thereof
(page 7 lines 14-25). The consequences of KCN are as variable as its epidemiology, ranging
from mild astigmatism to severely distorted vision. However, treatment options are surprisingly
limited. Most mild KCN can be corrected with glasses or soft contacts but very often patients
will need toric or hard contacts as the disease progresses. Ultimately, 1 in 5 patients will require
surgery, most commonly deep anterior lamellar keratoplasty or a penetrating corneal transplant.
Such procedures require considerable costs and entail significant risk of intraoperative and postoperative complications (bleeding, scarring, cataract formation, etc.). Thus, more effective presurgical treatment options are desperately needed. Intacs ( clear crescent-shaped pieces of plastic polymer) have been used as a treatment option for mild to moderate keratoconus. These
intrastomal corneal rings are inserted as a minimally invasive procedure and have a 74% success
rate at restoring 20/20 best-corrected vision. However, cost and risk (neovascularization, channel
deposits, secondary surgery etc.) are again limiting. Methods to strengthen collagen cross-links
have also been attempted. Corneal Collagen Cross-link (CXL) therapy is a well-tolerated
technique where riboflavin drops are applied over or under the corneal epithelium and
ultraviolet-A light is then employed to release free oxygen radicals to strengthen collagen bonds.
This procedure has been shown to significantly delay or halt progression of KCN. Although this
technique carries minimal side-effects (the energy-rich UVA light and excessively high
concentration of free oxygen radicals can cause toxicity), it is still cost- prohibitive to many
subjects. The current disclosure describes an alternative composition, dosage form, and method
for strengthening collagen cross-links using a cross-linking agent, such as a copper-containing
agent, a calcium-containing agent, a magnesium-containing agent, a silver- containing agent, an
aluminum-containing agent, a zinc-containing agent, iron-containing agent, or other suitable
cross-linking agent. Some specific, but non-limiting, examples of cross- linking agents can
include acai extract, decorin, copper (II) sulfate, or combinations thereof. In some examples, the
cross-linking agent can be or include any divalent or multivalent ion or compound that is suitable
to induce or facilitate cross- linking in the cornea (page 8 lines 1-30). The copper- containing
agent can also be administered with a therapeutically effective amount of a second active or
therapeutic agent. Such additional agents can include riboflavin, rose bengal, hydroxylysine, the
like, or combinations thereof (page 11 lines 17-19).
Ambati does not teach a secondary therapeutic agent as required by applicant's
definition.
The teachings of Ostrow are related to ophthalmic compositions and methods of arresting
or preventing myopia development by administering to an eye of an individual in need thereof an
effective amount of an ophthalmic composition as described herein (Abstract). The ophthalmic
composition comprises from about 0.001 wt.% to about 0.05 wt.% of a muscarinic antagonist
and deuterated water, at a pD of from about 4.2 to about 7.9 (paragraph 0003). The muscarinic
antagonist includes atropine (paragraph 0004). In one embodiment, the composition is in the
form of an aqueous solution (paragraph 0014). The ophthalmic composition is formulated as an
ophthalmic solution for the treatment of an ophthalmic disorder. In some embodiments, the
ophthalmic disorder or condition is pre-myopia, myopia, or progression of myopia. In some
embodiments, the ophthalmic composition is formulated as an ophthalmic solution for the
treatment of pre-myopia, myopia, or progression of myopia (paragraph 0029). The composition
is a solution (paragraph 0030). One embodiment teaches a method of arresting myopia
development that comprises administering to an eye of an individual in need thereof an effective
amount of the ophthalmic composition. One embodiment teaches a method of preventing myopia
development that comprises administering to an eye of an individual in need thereof an effective
amount of an ophthalmic composition described herein. In some embodiments, described herein
is a method of arresting or preventing myopia development, comprising administering to an eye
of an individual in need thereof an effective amount of an ophthalmic composition comprising
from about 0.001 wt.% to about 0.05 wt.% of a muscarinic antagonist and deuterated water, at a
pD of from about 4.2 to about 7.9 (paragraph 0031). Typical ophthalmic aqueous solutions are
packaged in eye drop bottles and administered as drops. For example, a single administration
(i.e. a single dose) of an ophthalmic aqueous solution includes a single drop, two drops, three
drops or more into the eyes of the patient. In some embodiments, one dose of the ophthalmic
aqueous solution described herein is one drop of the aqueous solution composition from the eye
drop bottle (paragraph 00187). Table 1 teaches an ophthalmic aqueous solution
PNG
media_image1.png
255
619
media_image1.png
Greyscale
(paragraph 00303).
The teachings of Ambati and Ostrow are related to methods of treating myopia
comprising topically administering an effective amount of a therapeutic agent to an eye of a
subject, and it would have been obvious to have combined their teachings because they are in the
same field of endeavor.
Regarding claims 1 and 10, it would have been prima facie obvious to a person of
ordinary skill in the art before the effective filing date of the claimed invention to have practiced a method of treating or preventing progression of myopia caused by KCN comprising
administering a therapeutically effective amount of a composition to an eye of a subject wherein
the composition comprises a copper-containing agent and a secondary therapeutic agent present
in amounts sufficient to treat myopic progression caused by KCN and a pharmaceutically acceptable carrier, with a reasonable expectation of success because Ambati teaches a method of
treating keratoconus (KCN), which is known to lead to progressive myopia, comprising
administering a therapeutically effective amount of a composition to an eye of a subject during a
treatment period, wherein the composition comprises a therapeutically effective amount of a
copper-containing agent that is sufficient to increase lysyl oxidase activity in an eye of a subject
or otherwise increase crosslinking in the cornea of the subject, a therapeutically effective amount
of a second active or therapeutic agent, and a pharmaceutically acceptable carrier. Ambati does
not teach a suitable second active or therapeutic agent. It would have been prima facie obvious to
a person of ordinary skill in the art to have selected atropine as the second active agent in
Ambati' s formulation, with a reasonable expectation of success because Ostrow teaches treating
myopia by administering an ophthalmic formulation comprising atropine to an eye of a subject.
The selection of a known material suitable for its intended purpose supports obviousness
and combining prior art elements according to known methods to obtain predictable results
supports obviousness.
It is prima facie obvious to combine two compositions each of which is taught by the
prior art to be useful for the same purpose, in order to form a third composition to be used for the
very same purpose .... [T]he idea of combining them flows logically from their having been
individually taught in the prior art." In re Kerkhoven, 626 F .2d 846, 850, 205 USPQ 1069, 1072
(CCPA 1980).
The selection of a known material based on its suitability for its intended use supported a
prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S.
327, 65 USPQ 297 (1945).
Regarding claim 2, it would have been obvious to have formed the composition in the
form of a gel, with a reasonable expectation of success because Ambati teaches gels as suitable
pharmaceutically acceptable carriers (page 11 lines 25-30).
Regarding claim 3, it would have been obvious to have formed the composition as a
sustained release composition configured to release the therapeutic agents over a predetermined
period of time, with a reasonable expectation of success because Ambati teaches formulating the
composition to biodegrade and provide controlled and sustained releases of the active agent over
a predetermined period of time (page 14 lines 25-27). It would have been obvious to have
formulated the composition to release the therapeutic agents for a period of from about 1 month
until the condition has been satisfactorily resolved with a reasonable expectation of success
because Ambati teaches that the treatment period lasts from about 1 month until the condition
has been satisfactorily resolved (page 16 lines 18-28). The claimed time period is obvious
because it overlaps with the prior art time range.
Regarding claim 4, it would have been obvious to have administered the composition to
the eye in dropwise manner or ocular instillation with a reasonable expectation of success
because Ambati teaches administering the composition in the form of a drop to an eye (page 15
lines 22-24) and Ostrow teaches administering the composition to an eye wherein the
composition is an eye drop composition. The drop would have spread to the cul-de-sac of the eye
and the conjunctiva fornix of the eye as a result of the administering.
Regarding claim 5, it would have been obvious to have administered the composition 1-4
times per day, where the dosage amount at teach time point is 5-50 uL, with a reasonable
expectation of success because Ambati teaches said frequency and dosage amounts (page 16
lines 14-17). It would have been obvious to have formulated the composition to provide from
about 0.0005 ug to about 0.5 ug of copper per administration event, with a reasonable
expectation of success because Ambati teaches said amounts as suitable (page 14 lines 9-13).
The claimed range is obvious because it overlaps with the prior art ranges, whether prior art
composition is administered 1, 2, 3, or 4 times per day. Once a day administration would deliver
about 0.0005 ug to about 0.5 ug of copper, twice per day administration would deliver 0.001-1
ug of copper, three times per day administration would deliver 0.0015-1.5 ug of copper, and four
times per day administration would deliver 0.002-2 ug of copper.
Regarding claim 6, it would have been obvious to have formulated the composition to
contain 0.001-0.05 wt.% atropine because Ostrow teaches said concentration range as a suitable
concentration range of atropine in an ophthalmic composition (paragraph 00303). A composition
having 0.001-0.05 wt.% of atropine is configured to deliver claimed amount of atropine to the
eye of the subject, absent evidence to the contrary.
Regarding claims 7 and 8, it would have been obvious to have formulated the
composition to comprise 0.001-0.05% of atropine, with a reasonable expectation of success
because Ostrow teaches 0.001-0.05 wt.% of atropine as a suitable concentration range of
atropine in an ophthalmic composition. The claimed ranges are obvious because they overlap
with 0.001-0.05 wt.%.
Regarding claim 9, it would have been obvious to have selected Ostrow's composition
from Example 1 in Ambati's composition because Ostrow teaches that the composition in
Example 1 is suitable for ophthalmic administration and teaches that the composition suitable for
treating myopia. The composition contains 0.01-0.5 mg/g of atropine and the composition is
mostly deuterated water. It would have been reasonable to conclude that the density of the
solution as about 1.11 g/mL because deuterated water is the main component of the composition,
and it was known that the density of deuterated water is 1.11 g/mL. Therefore, the concentration
of atropine in the solution in mg/mL would have been from about 0.009 mg/mL to about 0.45
mg/mL. the claimed concentration range is obvious because it overlaps with from about 0.009
mg/mL to about 0.45 mg/mL.
Regarding claims 11-13, Ambati teaches a container of about 0.5 ml to about 50 ml
where the container can hold a plurality of dosage forms or a single dosage form. In some
examples, about 0.005 mg to about 1 mg of the copper-containing agent can be included in the
container (page 15 lines 8-18). A 0.5 ml container would have a concentration of copper from
0.01 mg/ml to 2 mg/ml. A 50 ml container would have a concentration of copper from 0.0001
mg/ml to 0.02 mg/ml. The claimed concentration ranges are obvious because they overlap with
prior art concentration ranges.
Regarding claim 14, it would have been obvious to have selected copper sulfate as the
copper-containing compound, with a reasonable expectation of success because Ambati teaches
copper sulfate (page 9 lines 15-20).
Regarding claim 15, it would have been obvious to have formulated the carrier with
solubilizing agent, a tonicity agent, a pH adjuster, a thickener or gelling agent, a polymer or
polymeric matrix, a preservative, water, and combinations thereof, with a reasonable expectation
of success because Ambati teaches said components as suitable for making a pharmaceutically
acceptable carrier (paragraph bridging pages 11-12).
Regarding claim 16, it would have been obvious to have formed the composition having
a tonicity of from about 250 to about 350 mOsm/L, with a reasonable expectation of success
because Ambati teaches said range as suitable (page 12 lines 13-19).
Regarding claim 17, it would have been obvious to have formed the pH of the
composition in the range of about 5.5 to about 8.5, with a reasonable expectation of success
because Ambati teaches from about 5.5 to about 8.5 as a suitable pH range of the composition
(page 12 lines 25-30).
Regarding claim 18, it would have been obvious to have administered the composition in
a dropwise manner at a drop volume of from about 5 ul to about 50 ul, with a reasonable
expectation of success because Ambati teaches said range as suitable (page 15 lines 22-24). The
claimed range is obvious because it overlaps with the prior art range.
Regarding claim 19, Ambati teaches a container of about 0.5 ml to about 50 ml where the
container can hold a plurality of dosage forms or a single dosage form. In some examples, about
0.005 mg to about 1 mg of the copper-containing agent can be included in the container (page 15
lines 8-18). A 0.5 ml container would have a concentration of copper from 0.01 mg/ml to 2
mg/ml. A 50 ml container would have a concentration of copper from 0.0001 mg/ml to 0.02
mg/ml. It would have been obvious to have administered the composition in a dropwise manner
at a drop volume of from about 5 ul to about 50 ul, with a reasonable expectation of success
because Ambati teaches said range as suitable (page 15 lines 22-24).
A 5 ul (equivalent to 0.005 ml) drop having a copper concentration of from 0.0001 mg/ml
to 2 mg/ml would deliver 0.0000005 mg to 0.01 mg of copper. A 50 ul (equivalent to 0.05 ml) drop having a copper concentration of from 0.0001 mg/ml to 2 mg/ml would deliver 0.000005 mg to 0.1 mg of copper. The claimed range is obvious because it overlaps with the prior art range.
Regarding claim 20, it would have been obvious to have administered the composition
from 1 to 4 time points per day per eye in need thereof, with a reasonable expectation of success
because Ambati teaches 1-4 times per day as a suitable administration frequency. A person
skilled in the art would have recognized that the administration schedule is per eye in need of
treatment.
Regarding claim 21, it would have been obvious to have administered the composition in
a dropwise manner at a drop volume of from about 5 ul to about 50 ul, with a reasonable
expectation of success because Ambati teaches said range as suitable (page 15 lines 22-24). Each
administration time point would have required at least one drop, which would have provided 5-
50 ul of the composition. The claimed range is obvious because it overlaps with the prior art
range.
Regarding claim 23, it would have been obvious to have treated a patient of 10-30 years
old, with a reasonable expectation of success because Ambati teaches treating children and
teenagers of ages 10-18, and adults of age 18-30 (page 16 lines 18-25).
Regarding claim 24, it would have been obvious to have treated a patient for a period
form about 6 months to about 12 months or until the conditions has been satisfactorily resolved
(page 16 lines 25-28).
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Ambati and Ostrow
as applied to claims 1-21, 23, and 24 above, and further in view of Wesley (WO 98/52090
Published November 19, 1998).
The claim further defines the method of claim 1.
The teachings of Ambati and Ostrow are relied upon as described above. They do not
teach an ocular-shaping device configured to re-shape an elongated myopic eye.
The teachings of Wesley are related to a device for creating an imprint on the eye
comprising a first zone for facilitating tear exchange, a second zone defining a pressure curve, a
third zone defining a relief area for receiving the cornea displaced from the second zone, and a
fourth zone defining a base curve for imparting outward pressure on the eye (Abstract). In one
embodiment, a contact lens that can be used for orthokeratology is provided (page 5 lines 20-21).
One embodiment provides a lens that can be used to reshape the cornea of a myopic patient (paragraph bridging pages 12-13).
The teachings of Wesley and Ambati modified by Ostrow are related to methods of
treating myopia, and it would have been obvious to have combined them because they are in the
same field of endeavor. It would have been obvious to have administered Ambati's composition
modified by Ostrow using a lens, with a reasonable expectation of success because Ambati
teaches that a contact lens may be used to administer the composition (page 11 lines 25-32). It
would have been obvious to have selected a lens for reshaping the cornea of a myopic eye, with a
reasonable expectation of success because a lens for reshaping cornea of a myopic patient was
known from Wesley. The selection of a known material based on its suitability for its intended
purpose supports obviousness and combining prior art elements according to known methods to
obtain predictable results supports obviousness.
Double Patenting Rejections
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 Langi, 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 l.32l(c) or l.32l(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 l.32l(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 LB. I. For a reply to a non-final Office action, see 37 CFR 1.11 l(a). For a reply to final Office action, see 3 7 CFR 1.113 (c). A request for reconsideration while not provided for in 3 7 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/ AIN26) 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 autoprocessed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-24 are provisionally rejected on the ground of nonstatutory double patenting as
being unpatentable over claims 1-29 of copending Application No. 18/546,258 in view of
Wesley, Ambati, and Ostrow. The teachings of copending claims and prior art references are
related to methods of treating myopia. It would have been prima facie obvious to a person of
ordinary skill in the art before the effective filing date of the claimed invention to have modified
the method in copending claims with the teachings of Ambati and Ostrow to arrive at the
invention of present claims 1-21, 23, and 24, with a reasonable expectation of success for the
same reasons described in detail above. It would have been further obvious to have modified the
method of copending claims as modified by Ambati and Ostrow by Wesley in order to arrive at
the invention of present claim 22, with a reasonable expectation of success for the same reasons
as described above in the rejection.
This is a provisional nonstatutory double patenting rejection.
Claims 1-24 are provisionally rejected on the ground of nonstatutory double patenting as
being unpatentable over claims 1-21 of copending Application No. 18/080,466 in view of
Wesley, Ambati, and Ostrow. The teachings of copending claims are related to compositions for
treating myopia and prior art references are related to methods of treating myopia. It would have
been prima facie obvious to a person of ordinary skill in the art before the effective filing date of
the claimed invention to have utilized the composition of copending claims in a method of
treating myopia, with a reasonable expectation of success because the intended use of the
claimed composition is treatment of myopia. It would have been obvious to have treated the
myopia using the method steps of Ambati and Ostrow because these references are concerned
with methods of treating myopia. It would have been obvious modified the copending claims
with the teachings of Ambati and Ostrow to arrive at the invention of present claims 1-21, 23,
and 24, with a reasonable expectation of success for the same reasons described in detail above.
It would have been further obvious to have modified the method of copending claims as
modified by Ambati and Ostrow by Wesley in order to arrive at the invention of present claim
22, with a reasonable expectation of success for the same reasons as described above in the
rejection.
This is a provisional nonstatutory double patenting rejection.
Claims 1-24 rejected on the ground of nonstatutory double patenting as being
unpatentable over claims 1-19 of U.S. Patent No. 11,524,032 (of record in IDS dated 02/15/2023) in view of Wesley, Ambati, and Ostrow. The teachings of patented claims and prior art references are related to methods of treating myopia. It would have been prima facie obvious
to a person of ordinary skill in the art before the effective filing date of the claimed invention to
have modified the method in patented claims with the teachings of Ambati and Ostrow to arrive
at the invention of present claims 1-21, 23, and 24, with a reasonable expectation of success for
the same reasons described in detail above. It would have been further obvious to have modified
the method of patented claims as modified by Ambati and Ostrow by Wesley in order to arrive at
the invention of present claim 22, with a reasonable expectation of success for the same reasons
as described above in the rejection.
Claims 1-24 rejected on the ground of nonstatutory double patenting as being
unpatentable over claims 1-13 of U.S. Patent No. 11,065,275 in view of Wesley, Ambati, and
Ostrow. The teachings of patented claims are drawn to methods of treating keratoconus and prior
art references are related to methods of treating myopia. As evidenced by Ambati, keratoconus
leads to progressive myopia. Thus, it would have been obvious to treat myopia using the method
of patented claims. It would have been prima facie obvious to a person of ordinary skill in the art
before the effective filing date of the claimed invention to have modified the method in patented
claims with the teachings of Ambati and Ostrow to arrive at the invention of present claims 1-21,
23, and 24, with a reasonable expectation of success for the same reasons described in detail
above. It would have been further obvious to have modified the method of patented claims as
modified by Ambati and Ostrow by Wesley in order to arrive at the invention of present claim
22, with a reasonable expectation of success for the same reasons as described above in the
rejection.
Response to Arguments
Applicant's arguments, that are relevant to Ambati, submitted in the remarks dated
October 17, 2025 were fully considered, but are not persuasive for the following reasons.
Applicant's argument that Ambati does not teach treating or preventing progression of
myopia at all, is not persuasive because based on the phrase "the disease manifests itself in the
second decade of life when the cornea assumes a more conical shape, which leads to irregular
astigmatism, progressive myopia, ... ", a person skilled in the art would have understood that KCN manifests in the second decade of life when the cornea assumes a more conical shape, which leads to progressive myopia. In other words, KCN becomes apparent or obvious when the cornea assumes a conical shape which leads to progressive myopia. The conical shape of the cornea is a result of KCN disease. To further show that examiner's interpretation of Ambati's background section is correct, the following references are provided as evidence:
"Keratoconus" (https:/Awww.cedars-sinai.org/health-library/diseases-and-
conditions/k/keratoconus.html, accessed May 23, 2025, pages 1-6 – of record in PTO-892 dated
May 29, 2025) and
"Why Keratoconus Causes Nearsightedness" (https://keratoconustreatments.com/ whykeratoconus-causes-nearsightedness/, Accessed May 23, 2025, pages 1-4 - ofrecord in PTO-892 dated May 29, 2025).
"Keratoconus" teaches that keratoconus is an eye disorder in which the cornea thins over time. The cornea also bulges out to form a conelike shape. These changes in the cornea can cause
vision problems such as myopia and astigmatism (page 1). Keratoconus causes myopia (page 2).
"Why Keratoconus Causes Nearsightedness" teaches that the normally round-shaped cornea is
elongated into a cone-shape in keratoconus. Not only does the abnormally shaped cornea cause
myopia in a person with keratoconus, but it can cause other vision impacting symptoms such as
sensitivity to sunlight (page 2).
Applicant stated that the passage in Ambati indicates a correlation between KCN and progressive myopia in that they both occur when the cornea assumes a more conical shape.
This argument is not persuasive because KCN is a condition where the cornea thins and bulges outward creating a conelike shape. This meaning is apparent from the word keratoconus, which means cone-shaped cornea. The examiner maintains that keratoconus or cone-shaped cornea causes myopia. The examiner is aware that not every person with myopia has keratoconus because keratoconus is not the only disease that causes the cornea to change from round to cone shape, which causes myopia.
Applicant stated that Ambati does not teach and it does not necessarily follow that administration of a copper-containing agent can treat progression of myopia. Ambati also does not teach that progression of myopia can be treated by increasing lysyl oxidase activity.
This argument is not persuasive because a patient having myopia caused by KCN has a weak cornea and Ambati’s treatment would strengthen the cornea by strengthening collagen crosslinks. Ambati teaches treating can be done to reduce, ameliorate, or eliminate symptoms associated with a condition present in a subject or can be prophylactic. Myopia is a symptom of KCN. Thus, it would have been obvious to treat myopia caused by KCN using Ambati’s method.
Applicant stated that KCN and myopia are different conditions, and while an individual may have both KCN and myopia, an individual may have myopia without KCN. Many individuals with myopia do not have KCN.
This argument is not persuasive because it is apparent from Ambati’s teachings that KCN causes progressive myopia. “Keratoconus” and “Why Keratoconus Causes Nearsightedness” teach that KCN causes myopia. The examiner agrees that KCN is not the only disease that causes myopia. Instant claims are broadly drawn to a method of treating or preventing progression of myopia without limiting the patient population by any particular root cause or diseases that causes the progression of myopia.
Applicant cited Ambati’s examples of treatment methods and stated that none of the examples describe the subjects as having myopia.
This argument is not persuasive because Ambati is not limited to exemplified embodiments.
Applicant argued that it would not have been obvious to use atropine as a secondary active agent. Ambati does not teach a method of treating myopia. Therefore, Ambati definitely does not teach using a secondary active agent for the treatment of myopia. Active agents have the ability to interact. Atropine has a different mechanism of action from Ambati’s corneal crosslinking agent and the skilled artisan would not be motivated to combine the two and would be lead away from using the combination.
The argument is not persuasive because Ambati teaches treating progressive myopia for reasons described above. Ambati also teaches that a secondary active agent may be used in the treatment method, thus Ambati intended to treat progressive myopia with a combination of active agents. Since Ambati does not limit the secondary active agent, it would have been obvious to select another active agent intended for treating progressive myopia and use in Ambati's method. There is no evidence on the record showing that atropine would not have been suitable for use with Ambati's copper active agent. The skilled artisan would have been capable of a selecting a secondary active agent and its concentration based on the teachings of the prior art. Since there is no reference on record teaching away from combining the copper active agent with a secondary active agent such as atropine, the examiner maintains that it would have been obvious to select another active agent, such as atropine, that is suitable for treating progressive myopia and combined with Ambati's copper active agent.
Applicant stated that the combination of Ambati and Ostrow would yield highly unpredictable results, would not only lead one skilled in the art with only trial and error to figure out how all of the variables and changes would impact eye sight, but would also easily lead to worsening the eye sight of the patient.
This argument is not found persuasive because it is not supported by evidence. Ambati does not limit the second therapeutic agent, and there is no evidence on the record that Ambati’s active agent and atropine would lead to worsening of the eye sight of the patient. The skilled artisan would have been capable of determining amounts and administration of the combination of active agents through routine experimentation.
In response to arguments against the rejection of claim 22, Ambati and Ostrow are not deficient for reasons described above.
Double patenting rejections are maintained because applicant requested the rejections to be held in abeyance.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 Alma - Pipic whose telephone number is (571)270-7459. The examiner can normally be reached M-F 9:00am-5:00pm. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview
Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's
supervisor, Michael Hartley can be reached on 571-272-0616. The fax phone number for the
organization where this application or proceeding is assigned is 571-273-8300. Information
regarding the status of published or unpublished applications may be obtained from Patent
Center. Unpublished application information in Patent Center is available to registered users. To
file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit
https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and
https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional
questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you
would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN
USA OR CANADA) or 571-272-1000.
/ALMA PIPIC/Primary Examiner, Art Unit 1617
Prosecution Insights