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 present application was filed July 26, 2022.
Status of the Claims
In the amendment filed June 24, 2026, claims 1 and 19 are amended. Claims 1, 3, 5-8, 12-13, 15, and 19 are pending.
Response to Amendment/Arguments
The amendments to claims 1 and 19 overcome the previous rejections of claims 1, 3, 5-8, 12-13, 15, and 19 under 35 U.S.C. § 112(a) for failure to satisfy the written description requirement, and those rejections are therefore withdrawn.
Claim Rejections - 35 USC § 112(b) – Necessitated by Amendment
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, 3, 5-8, 12-13, 15, and 19 are indefinite:
Claims 1, 3, 5-8, 12-13, 15, and 19 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 1 is indefinite for reciting “the subject having a Spherical Equivalent (SE) of an eye of more than or equal to+ 1.0 D,” in lines 8-9. This limitation is mutually exclusive with the limitation in lines 6-7 “wherein the subject has a Spherical Equivalent (SE) of an eye of 0 to + 1.0 D before administration of the composition.” This inconsistency renders claim 1 indefinite. Claims 3, 5-8, 12-13, 15, and 19 are indefinite for depending from claim 1 without curing this indefiniteness.
Claim Rejections - 35 USC § 103 – Necessitated by Amendment
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.
Claims 1, 3, 5-8, 12-13, 15, and 19 are unpatentable over Fang and Moon:
Claims 1, 3, 5-8, 12-13, 15, and 19 are rejected under 35 U.S.C. § 103 as being unpatentable over the non-patent publication, Prevention of myopia onset with 0.025% atropine in premyopic children, J. Ocul. Pharmacol. Ther., 26, pgs. 341-345 (2010) by Fang et al. (hereinafter, “Fang”), in view of the non-patent publication, The diluted atropine for inhibition of myopia progression in Korean children, Int. J. Ophthalmol., 11, pgs. 1657–1662 (2018) by Moon et al. (hereinafter, “Moon”).
Amended claim 1 recites a method for inhibiting or delaying the onset of myopia in a subject, the method being characterized by the following elements:
a step of administering to the non-myopic subject a composition comprising atropine;
where the atropine is 0.05%, and
with administration persisting for at least four, five, or six years (i.e. at least four years);
Wherein the subject is at least four years old and less than five years old (i.e. is four years old);
the subject has a Spherical Equivalent (SE) of an eye of 0 to +1.0 D prior to administration;
the subject has at least one myopic parent who has a Spherical Equivalent Refraction (SER) of less than or equal to -3.00 D;
the subject has no astigmatism or has astigmatism of less than 1.00 D before administration of the composition; and
“whereby the onset of myopia is delayed” due to administration of the atropine.
With respect to the final “whereby” clause of claim 1 (element (vi)), this is an intended result that cannot be given patentable weight in this instance. “A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Minton v. Nat'l Ass'n. of Sec. Dealers, 336 F.3d 1373, 1381 (Fed. Cir. 2003 – emphasis added to quotation). See also MPEP § 2111.04(I), which makes clear that this rule of claim construction is not limited to clauses marked off by the term “whereby,” but is applicable to functionally equivalent clauses having terms such as “wherein” or other functionally equivalent terms.
Fang teaches a study of the effects of dilute atropine administration in inhibiting the onset of myopia in children, including administration of 0.025% atropine eye drops to 24 pre-myopic subjects (Fang, pg. 342, second full paragraph). Fang further teaches that atropine administration was for a mean duration of 18.4±6.9 (range: 12–36) months (pg. 342 right column, 2nd & 3rd paragraphs). Fang thus teaches a method of inhibiting or delaying the onset of myopia in a subject comprising administering to the subject a composition comprising atropine (element (i)) and teaches that, in at least some cases, administration was for at least two or three years (not identical to element (ib)). Fang further teaches that several of the subjects have spherical equivalent (SE), as measured by cycloplegic refraction, within a range of from 0 to +1.0 D, before administration of the atropine composition (element (iii)). See modified FIG. 1 of Fang, below, showing SE of the subjects from the treatment group, before and after the follow-up period, with several subjects having a starting SE between 0 and 1.0 D.
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Modified FIG. 1 of Fang, showing only the Treatment group panel and omitting the Control group.
Regarding the limitation of amended claim 1 that the method involves administering atropine to specifically non-myopic subjects, as noted above, Fang teaches that premyopic subjects were selected having SER <+1 D, but >-1 D (pg. 342, left column, first paragraph). Fig. 1 of Fang confirms this, and shows that multiple subjects had initial SER greater than 0 D. These subjects are regarded as being non-myopic as that term is applied to instant claim 1. Regarding the limitation wherein the subject has no astigmatism or has astigmatism of less than 1.00 D before administration of the composition, Fang discloses that “[e]xclusion criteria included astigmatism 1 D or over,” (pg. 342, first partial paragraph) indicating that all subjects have astigmatism less than 1 D (element (v)).
With respect to the limitations that administration is for a duration of at least four years (element (ib)) and that the subject is four years old (element (ii)), Fang teaches administering atropine to premyopic (i.e. non-myopic) subjects for a period of up to 3 years, and that subjects are as young as six, but does not explicitly teach administering the atropine for about 4 years or where the patients are four. However, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783 (Fed. Cir. 1985). See also MPEP 2144.05(I). This is particularly so when there is no showing that the claimed range (in this case, at least about 4 years) is critical, and there is no evidence of record that either 4 years administration of atropine, or a starting age of four is necessary or important to yield a useful result that is not realized with 3 years administration or with a starting age of six (note that the Moon reference teaches subjects as young as five).
Furthermore, while Fang presents data with a maximum administration duration of 3 years, nothing in Fang would have suggested to a person of ordinary skill in the art that myopia-preventing atropine administration should be limited to a maximum of 3 years. As Applicant has previously noted, Fang is a retrospective study, and 3 years simply represents the maximum duration of administration for which data were available. In addition, Fang recognized that “younger children experience more myopia progression over a 3-year period,” but because early onset of myopia often leads to greater severity of myopia, “it is important to maintain hyperopic or premyopic status in schoolchildren.” Therefore, and especially when beginning administration with particularly young subjects, one of skill in the art would have recognized the utility of maintaining atropine concentration in premyopic children for a duration in excess of 3 years, such as about 4 years or more, in order to maintain hyperopic or premyopic status while the subjects remain schoolchildren, or until ocular stability is reached. By the same rationale, one would have recognized the utility of starting treatment at a young age, such as starting two years earlier than is shown in the retrospective study of Fang. As such, the at least 4 years administration and beginning age of four years of instant claim 1 are obvious variations of the 3 years administration and starting age of six of Fang (elements (ib) and (ii)). Similar reasoning is applied to claim 19, below.
Fang thus teaches, or renders obvious, a method for inhibiting or delaying the onset of myopia in a subject, including a step of administering, for at least two or three years (obviously extendable to 4 years), to the non-myopic child subject aged six (obviously adjustable to age four) a composition comprising atropine. Fang also teaches that the subject has SE of an eye of 0 to +1.0 D prior to administration and has no astigmatism or has astigmatism of less than 1.00 D before administration of the composition (elements (i), (ib), (ii), (iii) and (v)). Fang does not explicitly teach the concentration of atropine administered being about 0.05% (element (ia)); or that the subject has at least one myopic parent that has a Spherical Equivalent Refraction (SER) of less than or equal to -3.00 D (element (iv)). With respect to the former, although Fang teaches 0.025% atropine administration and not the claimed 0.05% atropine, one of ordinary skill in the art would have a reasonable expectation of success in using 0.05% atropine because both were known to be safe and effective in pediatric patients. It was further a known practice in the art to administer atropine to children who have at least one myopic parent. See, for example, Moon.
Moon teaches a study of the ability of low concentration atropine to slow the progression of myopia in myopic children. Moon teaches the use of three low concentration atropine solutions, including the 0.025% atropine as in Fang, but also the claimed 0.05% atropine (Moon, pg. 1658, first through third full paragraphs, and Table 1, reproduced below).
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Above: Moon, Table 1
One would have recognized atropine concentration as a result-effective variable, whether for inhibition of myopia progression (as shown explicitly by Moon) or for inhibition of myopia onset. This is because inhibition of myopia progression and inhibition of myopia onset, while distinct, are similar, and because drug dose is generally understood as being a result-effective variable in drug response (see, e.g. the definition of drug dose-response in the non-patent publication, Dose-response relationship, Ch. 3.6 of Pharmaceutical Medicine, ed. Kilcoyne et al., pgs. 132-135 (2013), stating, “The dose–response relationship is the measurement of the relationship between the dose of a substance administered and its overall effect.”) Accordingly, it would have been obvious to optimize the atropine concentration in the method of Fang, in particular by trying the 0.05% atropine already shown by Moon to be safe, with no adverse effects (pg. 1659, right column, first paragraph). This obviousness is further supported by, but does not rely upon, the teaching of Moon that 0.05% atropine is more effective than 0.025% atropine for the distinct, but similar, purpose of inhibiting progression of already-onset myopia (element (ia)).
With respect to the feature of claim 1 in which the subject has at least one myopic parent that has a Spherical Equivalent Refraction (SER) of less than or equal to -3.00 D (element (iv)), Table 1 of Moon indicates that 36 of the subjects who received 0.05% atropine had a family history of high myopia. Moon further discloses (pg. 1658, third full paragraph) that, “[a] family history of high myopia was defined when any one of the parents showed more than −6.0 D myopia.” The expression “more than −6.0 D myopia” in the cited context from Moon is construed as indicating a negative SE greater in magnitude than, or more negative than, −6.0 D. It is noted that the instant Specification, states at pg. 6, lines 14-16, that, “[a]s used herein, the term ‘myopia’ refers to a subject having at least one eye with a Spherical Equivalence (SE) value less than or equal to −0.5 D, such as, for example, −1.0 D, −2.0 D.” Consistent with this, the phrase “less than or equal to -3.00 D” as used in instant claim 1 is construed to include numbers more negative than −3, and to exclude numbers less negative than −3.
Fang, as modified by Moon, thus discloses or renders obvious all elements (i), (ia), (ib), (ii), (iii), (iv), and (v) of claim 1.
With respect to claim 3, Fang teaches that the SE is measured by cycloplegic autorefraction after administration of a cycloplegic agent (pg. 342, left column, third paragraph, and Modified FIG. 1, above).
With respect to claims 5-7, Fang discloses that subjects “received topical 0.025% atropine eye drops at bedtime every night during the course of their follow-ups.” (see Fang, pg. 342, second full paragraph). This indicates that the composition is (i) administered at least once daily (claim 5), (ii) administered as eye drops (claim 6), and (iii) at least one drop is administered to the eye (claim 7). Similarly, Moon discloses that, “[t]he eye drops were used daily before bedtime.” Thus, administration is at least once daily (claim 5), administered to an eye of the subject (claim 6), and at least one eye drop is administered (claim 7).
With respect to claim 8, while Fang is silent as to the volume of the administered eye drops, it is noted that the volume of a drop of water, or aqueous solution, is well known to generally be about 50 µL (see e.g. the web page “What is the Volume of One Drop of Water”, available at the time of this writing at the URL, www.reference.com/science-technology/volume-one-drop-water-8164b654ac639858, stating that “A drop of water is equal to 0.050 milliliters.” See also TABLE 1 (reproduced below), from the non-patent publication, Determinants of Eye Drop Size, Surv. Ophthalmol., 49, pgs. 197-213 (2004) by Van Santvliet et al. (hereinafter, “Van Santvliet”), showing that, under a variety of conditions, eye drops extruded from a plastic dropper bottle are within the recited range. It can thus be inferred that eye drops administered during the study of Fang are, inherently, within the volume range recited in claim 8.
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Above: TABLE 1 from Van Santvliet.
With respect to claims 12 and 13, Moon discloses that the atropine solutions for administration were prepared by diluting a 1% atropine eye drop solution with 0.9% normal saline (Moon, pg. 1658, third full paragraph), so that the administered solution includes a sodium chloride excipient, as defined by claim 13, which is thus also an excipient of claim 12.
With respect to claim 15, Moon discloses that subjects, “with anisometropia of SE > 2.0 D…were excluded,” and thus the preponderance of subject of Moon have anisometropia of less than 2.00 D before administration of the composition.
With respect to claim 19, the element where atropine administration is over a period from about five to six years is obvious over the 2-3 years of Fang, because there is no showing that the recited range is critical to the operation of the method. “The law is replete with cases in which the difference between the claimed invention and the prior art is some range or other variable within the claims….In such a situation, the applicant must show that the particular range is critical, generally by showing that the claimed range achieves unexpected results relative to the prior art range.” In re Woodruff, 919 F.2d 1575 (Fed. Cir. 1990). Furthermore, “a modification of a process parameter may be patentable if it ‘produce[s] a new and unexpected result which is different in kind and not merely in degree from the results of the prior art.” E.I. DuPont de Nemours & Company v. Synvina C.V., 904 F.3d 996, 1006 (Fed. Cir. 2018). In the present case, there is no showing that administration of atropine to non-myopic children for a duration of 5-6 years, rather than for 2-3 years is critical, such as by showing that it produces an unexpected result or a result which is different in kind and not merely in degree from the results of the prior art. As such, the method of claim 19 is an obvious variation of the method of Fang and Moon.
Conclusion
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 ALEXANDER K SHOWALTER whose telephone number is (571)270-0610. The examiner can normally be reached M-F 9:00 am to 5:00 pm, eastern time.
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/ALEXANDER K. SHOWALTER/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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