DETAILED ACTION
Election/Restrictions
Applicant’s election of retinitis pigmentosa as the visual disorder due to a mutation in the RPE65 gene in the reply filed on 09/10/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
It is noted that Retinitis Punctata Albesciens is rejoined as it is a form of retinitis pigmentosa. Upon review the species for the disease condition is expanded to include Leber’s congenital amaurosis caused by a RPE65 mutation to address the broad breath claimed.
Status of Application
Applicant has elected retinitis pigmentosa as the visual disorder due to a mutation in the RPE65 gene for the examination.
Upon review the species for the visual disorder is expanded to include Leber’s congenital amaurosis caused by a RPE65 mutation to address the broad breath claimed.
Due to restriction, based on election and expanded visual disorder addressed above, claim 23 is withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claims 1-2, 4, 11, 13, 23-24, 26-29, 35 are pending.
Claims 1-2, 4, 11, 13, 24, 26-29, 35 are present for examination at this time.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2, 4, 11, 24, 26-29, 35 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.
The independent claim and its dependent claims are direct to a daily dosage to the human subject for “an extended period of time without a resting period” which is indefinite as it is unclear what the extended period of time is. Is it 8 hours? Is it 24 hours? Is it 3 days? Is it 7 days? Is it 10 day? Is it 14 days? 17days? It is not defined in the specification. It does not allow one to ascertain the metes and bounds of the claimed invention. For purposes of examination, any time period greater than 24 hours (a day, daily dosage) applies.
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.
Claims 1, 11, 24, 26-28, 35 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Koenekoop et al. (Oral 9-cis retinoid for childhood blindness due to Leber congenital amaurosis caused by RPE65 or LRAT mutations: an open-label phase 1b trial).
The claims as written are so broad as to read on the following prior art.
Rejection:
Koenekoop et al. teaches treating Leber congenital amaurosis (includes RPE65 mutation, has vision loss/impairment in visual field) in human patients with the oral administration of QLT091001 (synthetic 9-cis-retinyl acetate) once a day for 7 days at 10mg/m2 (is about 18.5mg, as standard man surface area is 1.85sq m (see K Zone for standard man) =10x1.85=18.5mg). Improvement was tested and measured by various means including Goldmann visual fields with an improvement in both eyes (i.e. Patients 8 and 9).
All the critical elements are taught by the cited reference and thus the claims are anticipated.
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.
Claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over Koenekoop et al. (Oral 9-cis retinoid for childhood blindness due to Leber congenital amaurosis caused by RPE65 or LRAT mutations: an open-label phase 1b trial) as applied to claims 1, 11, 24, 26-28, 35 above, in view of Ora, Inc. (Ora®, Inc. has been retained by ProQR Therapeutics to provide mobility test services using the Ora-VNC™ for the QR-110 development program for Leber's Congenital Amaurosis Type 10).
Rejection:
The teachings of Koenekoop et al. are addressed above.
Koenekoop et al. does not expressly teach measuring the improvement from the treatment using a visual navigational challenge test, but does teach treating the Leber congenital amaurosis with 9-cis retinyl acetate orally daily for 7 days at the recited dose and measuring the improvement present.
Ora, Inc. teaches that standardized mobility test services (also called visual navigation challenges) for Leber congenital amaurosis testing are known and can be provided.
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize visual navigation challenges to test the improvement with treatment as suggested by Ora, Inc. and produce the claimed invention; as it is prima facie obvious to utilize known standardized means to measure the improvement of treatment of Leber’s congenital amaurosis with a reasonable expectation of success. The improvement amount/score would be expected to be the same as the amount of improvement necessarily flows from the teachings of the applied prior art as it is the natural result of the same 9-cis retinyl acetate that is orally administered for the Leber congenital amaurosis at a dose and period that is within the instant claims.
Claims 1-2, 4, 11, 13, 24, 26-27, 35 are rejected under 35 U.S.C. 103 as being unpatentable over Palczewski et al. (WO 2006/002097).
Rejection:
Palczewski et al. teaches a method of treating Retinitis Punctata Albesciens (a form of retinitis pigmentosa, an impairment in visual field with loss of night vision and contrast sensitivity) in a human with a synthetic retinal derivative including 9-cis retinyl acetate (claims 56-62 and 19, 22-23, 27, 38, 40, 42-45).
The retinal can be locally administered to the eye via conventional forms like eye drops and injections (claims 24-25, 61), and orally (claim 26, 62). Other forms include a time/control release formulation such as implants with the inclusion of a slow release polymer like collagen [119].
The dosage range for eye drop can be about 0.01mg to about 25mg per single dose and administered one or more times/day as needed [121]. Orally it can be about 1.0-about 1000mg, which can be given 1-4x or more/day, an example is about 10-about 250mg, 1-3x/day [122-123]. Palczewski also teaches that the methods of using these compounds are to restore the photoreceptor function [11] and “restore” refers to long term improvement of the photoreceptor function in the visual system, such as in weeks or months ([107], extended period of time, see full document, specifically areas cited).
While Palczewski does not teach the exact claimed values for the dosage of 9-cis retinyl acetate; they are either embraced by the general range taught by the prior art (i.e. 0.01mg to about 25mg one or more times/day) wherein optimization within the taught range is not inventive as a means to attain the desired therapeutic effect, or they overlap (i.e. about 10-about 250mg, 1-3x/day) where even a slight overlap in range establishes a prima facie case of obviousness and would be obvious to modify the amount to attain the desired therapeutic effect, absent evidence of criticality or unexpected results.
Palczewski does not expressly teach the exact duration of treatment of the instant dependent claim (e.g. at least 30 days (one month), at least 90 days (3months), instant claim 13), but does teach the treatment to restore the photoreceptor function which is long term improvement such as in weeks or months ([107] an extended period of time); wherein it would be prima facie obvious to one of ordinary skill at the time of the invention to give the treatment for as long as needed to achieve the desired therapeutic effect to treat the condition (e.g. several months) and then either to stop the treatment upon resolution the condition, or to optimize the level/dosing protocol to achieve a maintenance dose and schedule to maintain the therapeutic effect if complete resolution is not possible but achieving stable maintenance of a chronic condition is; as this is the routine and customary protocol in the medicinal art for addressing an undesirable condition, particularly as Palczewski addresses that it is directed to a long term improvement measured in months, absent evidence of criticality of the time frame claimed.
Claims 28-29 are rejected under 35 U.S.C. 103 as being unpatentable over Palczewski et al. (WO 2006/002097) as applied to claims 1-2, 4, 11, 13, 24, 26-27, 35 above, in view of Shapiro et al. (Development and Validation of a Portable Visual Navigation Challenge for Assessment of Retinal Disease in Multi-Centered Clinical Trials).
Rejection:
The teachings of Palczewski et al. are addressed above.
Palczewski et al. does not teach using a visual navigational challenge to assess the improvement from treatment.
Shapiro et al. teaches that Ora-VNC™ is a visual navigation challenge that is designed to assess and create a metric that provides a reproducible measure of functional vision for patient with vision loss from an inherited retinal disease like retinitis pigmenta (retinitis pigmentosa). The course is mobile and designed to assess the visual function in a simulated “real-world” setting.
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize the Ora-VNC 360 visual navigation challenge to evaluate the improvement with treatment as suggested by Shapiro et al. and produce the claimed invention; as it is prima facie obvious to utilize a known means to measure the amount of functional vision to evaluated the improvement of treatment of an inherited retinal disease like retinitis pigmentosa (retinitis punctata albesciens is a form of retinitis pigmentosa) with a reasonable expectation of success. The improvement amount/score would be expected to be the same as the amount of improvement necessarily flows from the teachings of the applied prior art as it is the natural result of the same 9-cis retinyl acetate that is administered for the recited eye condition at a dose and time period within the instant claims.
Claims 28-29 are rejected under 35 U.S.C. 103 as being unpatentable over Palczewski et al. (WO 2006/002097) as applied to claims 1-2, 4, 11, 13, 24, 26-27, 35 above, in view of Ora (Ora-VNC™ Mobility Courses).
Rejection:
The teachings of Palczewski et al. are addressed above.
Palczewski et al. does not teach using a visual navigational challenge to assess the improvement from treatment.
Ora teaches that Ora-VNC™ Mobility Courses are designed to assess mobility and functional vision in patient with inherited retinal diseases like retinitis pigmentosa using a 360 degree visual challenge environment (visual navigational/mobility challenge) that has a standard protocol and objective scoring.
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize the Ora-VNC 360 degree visual challenge (visual navigation challenge) to evaluate the improvement with treatment as suggested by Ora and produce the claimed invention; as it is prima facie obvious to utilize a known means to measure the improvement of treatment of an inherited retinal disease like retinitis pigmentosa (retinitis punctata albesciens is a form of retinitis pigmentosa) with a reasonable expectation of success. The improvement amount/score would be expected to be the same as the amount of improvement necessarily flows from the teachings of the applied prior art as it is the natural result of the same 9-cis retinyl acetate that is administered for the recited eye condition at a dose and time period within the instant claims.
Conclusion
Claims 1-2, 4, 11, 13, 24, 26-29, 35 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GIGI GEORGIANA HUANG whose telephone number is (571)272-9073. The examiner can normally be reached Monday-Thursday 9:00-5:00pm.
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/GIGI G HUANG/Primary Examiner, Art Unit 1613