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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/23/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Amendment
This office action is responsive to the amendment filed on 12/23/25. As directed by the amendment: claims 1 and 68 have been amended. Claims 2, 4-9, 11, 16-20, 22-35, 41, and 44-65 are cancelled.
Thus, claims 1, 3, 10, 12-15, 21, 36-40, 42, 43 and 66-72 are pending in this application.
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.
Claim 68, 70-72 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 68 recites the limitation "the viral vector" in line 4. There is insufficient antecedent basis for this limitation in the claim.
By virtue of dependency, claims 70-72 are rejected.
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.
Claims 1, 3, 10, 12-15, 21, 36-38, 43 and 66-72 are rejected under 35 U.S.C. 103 as being unpatentable over Eyevensys (WO 2014125463 A1).
Regarding claim 1, Eyevensys discloses a method for delivering a virus particle (page 15, lines 11-32 and page 16, lines 1-2) into a retinal cell (page 13, lines 18-23) of an eye of a subject, comprising: a) administering a para-retinal injection of the virus particle (page 13, lines 18-23 and page 16, lines 12-14); and ii) applying an electric current to the eye, concurrently with or after the para-retinal injection of the virus particle (page 8, lines 22-32; page 9, lines 1-15 and page 25, lines 24-31 and page 26, lines 1-5); wherein the virus particle comprises one or more capsid proteins encapsulating an expression vector encoding a therapeutic protein (page 16, lines 1-2, lentivirus, adenovirus and AVV has capsid proteins encapsulating an expression vector).
Eyevensys fails to teach said method comprising administering a para-retinal injection of the viral vector between 0 and 13 mm from a surface of the retina but discloses needle 40 can be designed in such a way that its distal end reach the ciliary muscle or the vitreous cavity, or the subretinal space, or the retina, or the pigment epithelium of the retina (page 13, lines 18-23).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to cause the method of Eyevensys to administer a para-retinal injection of the viral vector between 0 and 13 mm from a surface of the retina in the posterior vitreous cavity of the eye since it has been held that “where the only difference between the prior art and the claims was a recitation of relative dimensions of the claimed method and a method having the claimed relative dimensions would not perform differently than the prior art method, the claimed method was not patentably distinct from the prior art device” Gardner v. TEC Syst., Inc., 725F.2d 1338, 220 USPQ 777 (Fed. Cir. 1984), cert. denied, 469 U.S. 830, 225 SPQ 232 (1984). In the instant case, the method of Eyevensys would not operate differently with the claimed range and since the tip of the injection needle is designed to reach the retina. Thus, the method of Eyevensys would function appropriately having the claimed range. Further, applicant places no criticality on the range claimed, indicating simply that administering a para-retinal injection of the viral vector between 0 and 13 mm from a surface of the retina in the posterior vitreous cavity of the eye (see specification).
Eyevensys fails to teach the electric current applied to the eye is between about 1.0 µA to 1,000 µA, 1,000 µA to 1,100 µA, 1,100 µA to 1,200 µA, 1,200 µA to 1,300 µA, or 1,300 µA to 1,400 µA but teaches current can be applied after injection (page 26, lines 1-10).
Therefore, it would have been obvious to one having ordinary skill in the art at the time of the invention to modify the current of Eyevensys by making the electric current applied to the eye is between about 1.0 µA to 1,000 µA, 1,000 µA to 1,100 µA, 1,100 µA to 1,200 µA, 1,200 µA to 1,300 µA, or 1,300 µA to 1,400 µA, concurrently with or after the para-retinal injection of the virus particle as a matter of routine optimization since it has been held that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding claim 3, Eyevensys discloses the method of claim 1, wherein the subject is being treated for an ophthalmic condition selected from the group consisting of Stargardt disease, X-linked retinoschisis, age-related macular degeneration (AMD), diabetic retinopathy, Leber congenital amaurosis (LCA), retinal detachment (due to disease, injury or spontaneous detachment), cysts, cystoid macular edema, retinitis pigmentosa, senile schisis, Fuchs corneal dystrophy and other corneal dystrophies, glaucoma, and cataract (page 19, lines 13-34).
Regarding claim 10, Eyevensys discloses the method of claim 1, as discussed above but fails to teach wherein the para-retinal injection is between 0 and 3 mm from the surface of the retina in the posterior vitreous cavity of the eye.
Eyevensys discloses needle 40 can be designed in such a way that its distal end reach the ciliary muscle or the vitreous cavity, or the subretinal space, or the retina, or the pigment epithelium of the retina (page 13, lines 18-23).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to cause the method of Eyevensys to administer a para-retinal injection of the viral vector between 0 and 3 mm from a surface of the retina in the posterior vitreous cavity of the eye since it has been held that “where the only difference between the prior art and the claims was a recitation of relative dimensions of the claimed device and a device having the claimed relative dimensions would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device” Gardner v. TEC Syst., Inc., 725F.2d 1338, 220 USPQ 777 (Fed. Cir. 1984), cert. denied, 469 U.S. 830, 225 SPQ 232 (1984). In the instant case, the method of Eyevensys would not operate differently with the claimed range and since the tip of the injection needle is designed to reach the retina. Thus, the method of Eyevensys would function appropriately having the claimed range. Further, applicant places no criticality on the range claimed, indicating simply that administering a para-retinal injection of the viral vector between 0 and 3 mm from a surface of the retina in the posterior vitreous cavity of the eye (see specification).
Regarding claim 12, Eyevensys discloses the method of claim 1 as discussed above but fails to teach wherein the electric current applied to the eye is between 1,200 pA and 1,300 pA.
Eyevensys teaches current can be applied after injection (page 26, lines 1-10).
Therefore, it would have been obvious to one having ordinary skill in the art at the time of the invention to modify the current of Eyevensys by making the electric current applied to the eye is between about 1,200 pA and 1,300 pA, as a matter of routine optimization since it has been held that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding claim 13, Eyevensys discloses the method of claim 1 as discussed above but fails to teach wherein the electric current is applied to the eye for a period of between 1 minute and 60 minutes.
Eyevensys discloses the total duration of application of the electric field may be between 0.01 millisecond and 1 second, preferably between 0.01 and 500 milliseconds, more preferably between 1 and 500 milliseconds, even more preferably greater than 1 or 10 milliseconds. In a preferred embodiment, the total duration of application of the electric field is between 10 milliseconds and 100 milliseconds and is preferably of 20 milliseconds (page 26, lines 12-16).
Therefore, it would have been obvious to one having ordinary skill in the art at the time of the invention to modify the current of Eyevensys by making the electric current applied to the eye for a period of between 1 minute and 60 minutes, as a matter of routine optimization since it has been held that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding claim 14, Eyevensys discloses the method of claim 1, wherein the electric current applied to the eye is applied as a fixed current (page 26, lines 23-27, square waveform is considered a fixed current because both the amplitude and the pulse width remain constant over time).
Regarding claim 15, Eyevensys discloses the method of claim 1, wherein the electric current applied to the eye is applied as a current selected from the group consisting of a variable current, a pulsed current, and a biphasic current (page 26, lines 17-27).
Regarding claim 21, Eyevensys discloses the method of claim 1 as discussed above but fails to teach the current is applied to the eye in a time period between 30 seconds and 6 hours after injection of the virus particle.
Eyevensys discloses applying current to the eye after injection of the virus particle (page 25, lines 24-31 and page 26, lines 1-5).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to cause the current of Eyevensys to be applied to the eye in a time period between 30 seconds and 6 hours after injection of the virus particle since it has been held that “where the only difference between the prior art and the claims was a recitation of relative dimensions of the claimed device and a method having the claimed relative dimensions would not perform differently than the prior art device, the claimed method was not patentably distinct from the prior art device” Gardner v. TEC Syst., Inc., 725 F.2d 1338, 220 USPQ 777 (Fed. Cir. 1984), cert. denied, 469 U.S. 830, 225 SPQ 232 (1984). Further, applicant places no criticality on the range claimed, indicating simply that the time period between 30 seconds and 6 hours after injection of the virus particle (see specification).
Regarding claim 36, Eyevensys discloses the method of claim 1, wherein the electric current is applied to the eye by contacting the subject with at least a first (50) and a second electrode (40), wherein the first electrode (50) is placed in contact with the cornea of the eye of the subject (fig 1, electrode 50 contacts the cornea of the eye) and the second electrode (40) is placed in contact with a portion of the body of the subject (fig 1, electrode 40 comes in contact with the outside surface of the eye which a portion of the body).
Regarding claim 37, Eyevensys discloses the method of claim 1, wherein the electric current is applied to the eye by contacting the subject with at least a first (50) and a second electrode (40), wherein the first electrode is placed in contact with the cornea of the eye of the subject (fig 1, electrode 50 contacts the cornea of the eye) and the second electrode is placed in contact with a separate portion of the eye of the subject (fig 1, electrode 40 comes in contact with the outside surface of the eye).
Regarding claim 38, Eyevensys discloses the method of claim 37, wherein the second electrode (40) is placed in contact with a portion of the eye outside of the cornea of the subject (fig 1, electrode 40 comes in contact with the outside surface of the eye).
Regarding claim 43, Eyevensys discloses the method of claim 1, wherein the virus particle is expressed in a cell of the eye selected from the group consisting of photoreceptors and retinal pigment epithelia (RPE), retinal ganglion cells, Muller cells, horizontal cells, bipolar cells, nerve fiber layer structure, and amacrine cells (page 16, lines 12-14).
Regarding claim 66, Eyevensys discloses the method of claim 1, wherein the virus particle is a retrovirus, adenovirus, and/or neurotropic virus (page 16, lines 1-2).
Regarding claim 67, Eyevensys discloses the method of claim 1, wherein the virus particle is an adeno- associated virus (AAV) (page 16, lines 1-2).
Regarding claim 68, Eyevensys discloses a method for delivering a virus particle comprising a nucleic acid molecule encoding a therapeutic protein (page 15, lines 11-32 and page 16, lines 1-2) into a retinal cell (page 13, lines 18-23) of an eye of a human subject (page 1, lines 16-17, comprising: i) administering a para-retinal injection of the viral vector (page 13, lines 18-23 and page 16, lines 12-14); and ii) applying an electric current to the eye (page 8, lines 22-32; page 9, lines 1-15 and page 25, lines 24-31), by contacting the subject with at least a first (50) and a second (40) electrode, wherein the first electrode (50) is placed in contact with the cornea of the eye of the subject (fig 1, electrode 50 contacts the cornea of the eye) and the second electrode (40) is placed in contact with a portion of the body of the subject or a portion of the eye outside of the cornea of the subject (fig 1, electrode 40 comes in contact with the outside surface of the eye); and wherein the virus particle comprises one or more capsid proteins encapsulating an expression vector encoding the therapeutic protein (page 16, lines 1-2, lentivirus, adenovirus and AVV has capsid proteins encapsulating an expression vector).
Eyevensys fails to teach said method comprising administering a para-retinal injection of the viral vector between 0 and 13 mm from a surface of the retina but discloses needle 40 can be designed in such a way that its distal end reach the ciliary muscle or the vitreous cavity, or the subretinal space, or the retina, or the pigment epithelium of the retina (page 13, lines 18-23).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to cause the method of Eyevensys to administer a para-retinal injection of the viral vector between 0 and 13 mm from a surface of the retina in the posterior vitreous cavity of the eye since it has been held that “where the only difference between the prior art and the claims was a recitation of relative dimensions of the claimed method and a method having the claimed relative dimensions would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device” Gardner v. TEC Syst., Inc., 725F.2d 1338, 220 USPQ 777 (Fed. Cir. 1984), cert. denied, 469 U.S. 830, 225 SPQ 232 (1984). In the instant case, the method of Eyevensys would not operate differently with the claimed range and since the tip of the injection needle is designed to reach the retina. Thus, the method of Eyevensys would function appropriately having the claimed range. Further, applicant places no criticality on the range claimed, indicating simply that administering a para-retinal injection of the viral vector between 0 and 13 mm from a surface of the retina in the posterior vitreous cavity of the eye (see specification).
Eyevensys fails to teach the current is applied to the eye within 1 minute to 60 minutes after administering the para-retinal injection of the virus particle but discloses applying current to the eye after injection of the virus particle (page 25, lines 24-31 and page 26, lines 1-5).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to cause the current of Eyevensys to be applied to the eye i within 1 minute to 60 minutes after administering the para-retinal injection of the virus particle since it has been held that “where the only difference between the prior art and the claims was a recitation of relative dimensions of the claimed method and a method having the claimed relative dimensions would not perform differently than the prior art device, the claimed method was not patentably distinct from the prior art device” Gardner v. TEC Syst., Inc., 725 F.2d 1338, 220 USPQ 777 (Fed. Cir. 1984), cert. denied, 469 U.S. 830, 225 SPQ 232 (1984). Further, applicant places no criticality on the range claimed, indicating simply that the current is applied to the eye within 1 minute to 60 minutes after administering the para-retinal injection of the virus particle (see specification).
Eyevensys fails to teach the electric current applied to the eye is between 100 micro-ampere (pA) and 3,000 pA but teaches current can be applied after injection (page 26, lines 1-10).
Therefore, it would have been obvious to one having ordinary skill in the art at the time of the invention to modify the current of Eyevensys by making the electric current applied to the eye is between about 100 micro-ampere (pA) and 3,000 pA after the para-retinal injection of the virus particle as a matter of routine optimization since it has been held that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Eyevensys fails to teach wherein the electric current is applied to the eye for a period of between 1 minute and 60 minutes.
Eyevensys discloses the total duration of application of the electric field may be between 0.01 millisecond and 1 second, preferably between 0.01 and 500 milliseconds, more preferably between 1 and 500 milliseconds, even more preferably greater than 1 or 10 milliseconds. In a preferred embodiment, the total duration of application of the electric field is between 10 milliseconds and 100 milliseconds and is preferably of 20 milliseconds (page 26, lines 12-16).
Therefore, it would have been obvious to one having ordinary skill in the art at the time of the invention to modify the current of Eyevensys by making the electric current applied to the eye for a period of between 1 minute and 60 minutes, as a matter of routine optimization since it has been held that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding claim 69, Eyevensys discloses the method of claim 1, wherein the virus particle is delivered to the retina (page 13, lines 18-19).
Regarding claim 70, Eyevensys discloses the method of claim 68, wherein the virus particle is an adeno- associated virus (AAV) (page 16, lines 1-2).
Regarding claim 71, Eyevensys discloses the method of claim 68 as discussed above but fails to teach wherein the electric current is applied for a period of between 14 minutes and 46 minutes.
Eyevensys discloses the total duration of application of the electric field may be between 0.01 millisecond and 1 second, preferably between 0.01 and 500 milliseconds, more preferably between 1 and 500 milliseconds, even more preferably greater than 1 or 10 milliseconds. In a preferred embodiment, the total duration of application of the electric field is between 10 milliseconds and 100 milliseconds and is preferably of 20 milliseconds (page 26, lines 12-16).
Therefore, it would have been obvious to one having ordinary skill in the art at the time of the invention to modify the current of Eyevensys by making the electric current applied to the eye for a period of between 14 minutes and 46 minutes, as a matter of routine optimization since it has been held that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding claim 72, Eyevensys discloses the method of claim 68 as discussed above but fails to teach wherein the electric current is applied to the eye within 5 minutes after administering the para-retinal injection of the virus particle.
Eyevensys discloses applying current to the eye after injection of the virus particle (page 25, lines 24-31 and page 26, lines 1-5).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to cause the current of Eyevensys to be applied to the eye within 5 minutes after administering the para-retinal injection of the virus particle since it has been held that “where the only difference between the prior art and the claims was a recitation of relative dimensions of the claimed device and a method having the claimed relative dimensions would not perform differently than the prior art method, the claimed method was not patentably distinct from the prior art device” Gardner v. TEC Syst., Inc., 725 F.2d 1338, 220 USPQ 777 (Fed. Cir. 1984), cert. denied, 469 U.S. 830, 225 SPQ 232 (1984). Further, applicant places no criticality on the time claimed, indicating simply that the electric current is applied to the eye within 5 minutes after administering the para-retinal injection of the virus particle (see specification).
Claims 39 and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Eyevensys (WO 2014125463 A1) in view of Mohanty et al (US 20100268150 A1).
Regarding claim 39, Eyevensys discloses the method of claim 37 as discussed above but fails to teach wherein the first electrode is placed in contact with a portion of the eye inside the eye or vitreous.
However, Mohanty et al disclose a method for delivering a particle to the retina of the eye (abstract) comprising a first electrode (14) wherein the first electrode is placed in contact with a portion of the eye inside the eye or vitreous (fig 1 and para 0054).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Eyevensys and incorporate the teachings of Mohanty et al to have the first electrode placed in contact with a portion of the eye inside the eye to access the anterior region for the treatment of the posterior region of the eye (see para 0054).
Regarding claim 42, Eyevensys discloses the method of claim 1 as discussed above but fails to teach wherein the virus particle is delivered to the posterior segment of the eye by applying a negative voltage to the cornea, thereby allowing the virus particle to enter the retina.
However, Mohanty et al disclose a method for delivering a particle to the retina of the eye (abstract) comprising wherein the particle is delivered to the posterior segment of the eye by applying a negative voltage to the cornea, thereby allowing the virus particle to enter the retina (para 0023).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Eyevensys and incorporate the teachings of Mohanty et al to have the virus particle delivered to the posterior segment of the eye by applying a negative voltage to the cornea, thereby allowing the virus particle to enter the retina. This would provide the benefit of having a pulsed DC voltage with an optimized field strength amplitude, frequency, number of pulses, group repetition rate and duration of pulse and group repetition, which are optimized for delivering therapeutic agents in to the retina (see para 0023).
Claim 40 is rejected under 35 U.S.C. 103 as being unpatentable over Eyevensys (WO 2014125463 A1) in view of Behar-Cohen (US 20140309613 A1).
Regarding claim 40, Eyevensys discloses the method of claim 1 as discussed above, wherein the electric current is applied to the eye by contacting the subject with at least a first (40) and a second electrode (50), wherein both the first and the second electrodes are placed in contact with the eye of the subject (see fig 1) but fails to teach neither electrode is placed in contact with the cornea of the eye of the subject.
However, Behar-Cohen et al disclose a method for delivering a virus particle to the retina of the eye (para 0018) comprising a first electrode and a second electrode wherein neither electrode is placed in contact with the cornea of the eye of the subject (para 0052).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Eyevensys and incorporate the teachings of Behar-Cohen et al to have neither the first electrode and second electrode placed in contact with the cornea of the eye of the subject for the treatment of the posterior region of the eye (see para 0007 and 0052).
Response to Arguments
Applicant’s arguments, see Remarks, filed on 12/23/2025, with respect to the rejection(s) of claim(s) 1, 3, 10, 12-15, 21, 36-40, 42, 43 and 66-72 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Eyevensys (WO 2014125463 A1).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FATIMATA S DIOP whose telephone number is (571)272-3299. The examiner can normally be reached Monday- Friday, 9am to 6pm ET.
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, Bhisma Mehta can be reached at 571-272-3383. 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.
/FATIMATA SAHRA DIOP/ Examiner, Art Unit 3783 /BHISMA MEHTA/ Supervisory Patent Examiner, Art Unit 3783