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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 2-25-26 has been entered.
Claims 1-25, 27, 39, 42 have been canceled. Claims 46-48 have been added. Claims 26, 28-38, 40, 41, 43-48 are pending and under consideration.
Applicant's arguments filed 2-25-26 have been fully considered but they are not persuasive.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Objections
The steps of claim 26 can be delineated by “a)”, “b)” for ease of examination and discussion.
The phrase “to generate retinal ganglion cells (RGCs) that express the fusion protein” in claim 26 is an intended use and does not necessarily have to occur. If applicants are attempting to claim functional language that clearly MUST occur as a result of the “administering”, then use the phrase ---such that the fusion protein is expressed in retinal ganglion cells (RGCs) of the eye---.
The information about the fusion protein in lines 10-12 of claim 26 should be in step a) when the fusion protein is first introduced (lines 3-6).
The concept of “the tdT protein of the fusion protein contributes to the improvement of vision in the mammal” in lines 13-14 of claim 26 does not make sense. It is unclear if it is a comparison to Chrimson alone or to a fusion protein comprising Chrimson and a non-tdT protein. The claim already requires “such that vision is improved”, so it is unclear how to determine whether the tdT portion contributes to the improvement. Those of skill do not need to know or understand the mechanism of action or the contribution of tdT within the fusion protein to achieve the vision improvement. If applicants are attempting to claim a certain threshold of vision improvement by saying tdT contributes to vision improvement, then much clarification is required.
The meaning of a fusion protein with “higher firing rate frequency in the RGCs than Chrimson protein alone at a given light intensity of red light” in claim 26 cannot be determined. It cannot be determined whether that encompasses any Chrimson-tdT fusion protein. It is unclear whether the phrase is limited to a subset of Chrimson-tdT fusion proteins. Therefore, it is unclear whether the phrase further limits the structure of the Chrimson-tdT fusion proteins encompassed by the phrase or whether the phrase encompasses ANY Chrimson-tdT fusion protein.
The preamble does not need to refer to the mammal since the mammal is set forth in step a). Claim 26 can be written more clearly as ---A method for improving vision in a mammal, the method comprising:
a) administering a vector encoding a Chrimson-tdT fusion protein into an eye of a mammal that has photoreceptor loss and loss of vision; and b) stimulating the eye with red light such that vision is improved in the mammal---.
Claim 41 can be written more clearly and accurately as ---wherein the fusion protein comprises a Chrimson 88 protein comprising the amino acid sequence of SEQ ID NO: 1 or a Chrimson R protein comprising the amino acid sequence of SEQ ID NO: 2 fused to a tdT protein comprising the amino acid sequence of SEQ ID NO: 1---.
The phrase “restoring light sensitivity to a retina in the mammal” and the phrase “wherein the fusion protein contributes to the restoration of light sensitivity to the retina in the mammal” are redundant. Pick one or the other. Furthermore, claim 44 can be written more accurately as ---wherein the administering improves retina light sensitivity in the mammal---.
Claim 48 can be written more clearly for reasons set forth in claim 1.
Claim Rejections - 35 USC § 112
Written Description
Claims 26, 28-38, 40, 41, 43-48 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The specification lacks written description for a Chrimson-tdT fusion protein with “higher firing rate frequency in the RGCs than Chrimson protein alone at a given light intensity of red light” in claim 26. It cannot be determined whether that encompasses any Chrimson-tdT fusion protein. It is unclear whether the phrase is limited to a subset of Chrimson-tdT fusion proteins. Therefore, it is unclear whether the phrase further limits the structure of the Chrimson-tdT fusion proteins encompassed by the phrase or whether the phrase encompasses ANY Chrimson-tdT fusion protein. Accordingly, the specification lacks written description for a Chrimson-tdT fusion protein with “higher firing rate frequency in the RGCs than Chrimson protein alone at a given light intensity of red light” as required in claim 26.
The range of red light being 530-640 nm in claim 43 or 577-598 in claim 46 lacks written description. The wavelength of red light is 625-750. It does not include 626-640 as encompassed by claim 43 or 577-598 as required in claim 46. Accordingly, the claims lack written description.
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The specification lacks written description for a fusion protein with a firing rate of 2.34 x 1015 photons.cm.2.sec-1 in RGCs as required in claim 47. Applicants point to Fig. 3C for support, but the results are limited to specific 600 nm flashes for 2 seconds light stimulation and other conditions that are missing from the claims.
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Furthermore, the condition of “2.34 x 1015 photons.cm.2.sec-1” refers to the light intensity applied to the eye (“600nm-light flashes were applied on the retinal tissue for 2 sec with a light intensity increasing from 1.37 x 1014 to 6.78 x 1016 photons.cm2.sec-1”; pg 29, para 191). Finally, the control (Chrimson alone) and the test conditions (Chrimson-tdT) are both 2.34 x 1015 photons.cm.2.sec-1 in RGCs, so claiming it as being specific to Chrimson-tdT is meaningless. Only at higher light intensity are the conditions different. Accordingly, the concept lacks written description.
Enablement
Claims 26, 28-38, 40, 41, 43-48 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a) administering a vector encoding a Chrimson-tdT fusion protein into an eye of a mammal that has photoreceptor loss and loss of vision; and b) stimulating the eye with red light such that vision is improved in the mammal, does not reasonably provide enablement for a Chrimson-tdT fusion protein with “higher firing rate frequency in the RGCs than Chrimson protein alone at a given light intensity of red light” in claim 26. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
The specification does not enable making/using a Chrimson-tdT fusion protein with “higher firing rate frequency in the RGCs than Chrimson protein alone at a given light intensity of red light” as required in claim 26. It cannot be determined whether that encompasses any Chrimson-tdT fusion protein. It is unclear whether the phrase is limited to a subset of Chrimson-tdT fusion proteins. The specification and the art of no help in this regard. Therefore, it is unclear whether the phrase further limits the structure of the Chrimson-tdT fusion proteins encompassed by the phrase or whether the phrase encompasses ANY Chrimson-tdT fusion protein. Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to make/use any Chrimson-tdT fusion protein with “higher firing rate frequency in the RGCs than Chrimson protein alone at a given light intensity of red light” as required in claim 26.
The range of red light being 530-640 nm in claim 43 or 577-598 in claim 46 is not enabled. The wavelength of red light is 625-750 (see chart above). It does not include 626-640 as encompassed by claim 43 or 577-598 as required in claim 46. Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to perform the method of claim 43 or 46 as claimed.
The specification does not enable a fusion protein with a firing rate of 2.34 x 1015 photons.cm.2.sec-1 in RGCs as required in claim 47. Applicants point to Fig. 3C for support, but the results are limited to specific 600 nm flashes for 2 seconds light stimulation and other conditions that are missing from the claims (see figure above).
Furthermore, the condition of “2.34 x 1015 photons.cm.2.sec-1” refers to the light intensity applied to the eye (“600nm-light flashes were applied on the retinal tissue for 2 sec with a light intensity increasing from 1.37 x 1014 to 6.78 x 1016 photons.cm2.sec-1”; pg 29, para 191). Finally, the control (Chrimson alone) and the test conditions (Chrimson-tdT) are both 2.34 x 1015 photons.cm.2.sec-1 in RGCs, so claiming it as being specific to Chrimson-tdT is meaningless. Only at higher light intensity are the conditions different. Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to perform the method of claim 47.
Indefiniteness
Claims 26, 28-38, 40, 41, 43-45 remain and claims 46-48 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 metes and bounds of a fusion protein with “higher firing rate frequency in the RGCs than Chrimson protein alone at a given light intensity of red light” in claim 26 cannot be determined. It cannot be determined whether that encompasses any Chrimson-tdT fusion protein. It is unclear whether the phrase is limited to a subset of Chrimson-tdT fusion proteins. Therefore, it is unclear whether the phrase further limits the structure of the Chrimson-tdT fusion proteins encompassed by the phrase or whether the phrase encompasses ANY Chrimson-tdT fusion protein.
Claim 40 does not further limit claim 26. The phrase “fluorescent protein” was deleted in claim 26, and claim 26 is already limited to a fusion protein comprising Chrimson and tdT, so “wherein the fluorescent protein is td-Tomato (tdT)” fails to further limit claim 26.
Claim 43 does not further limit the “red light” in claim 26 because red light is from 625-700 nm:
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(Science Notes, 2026). Red light cannot be from 530-640 nm as required in claim 43 because that includes green, yellow, and orange light.
The phrase “restoring light sensitivity to a retina in the mammal” and the phrase “wherein the fusion protein contributes to the restoration of light sensitivity to the retina in the mammal” in claim 44 are redundant. If they do not have the same meaning, then the distinction between them cannot be determined.
Claim 46 does not further limit the “red light” in claim 26 because red light is from 625-700 nm (See Science Notes above, 2026). Red light cannot be from 577-598 nm as required in claim 46 because that includes yellow and orange light.
It is unclear how the phrase “the fusion protein produces the firing rate in the RGCs at an intensity of 2.34 x 1015 photons.cm2.sec-1 further limits the fusion protein in claim 26. The metes and bounds of a fusion protein with “higher firing rate frequency in the RGCs than Chrimson protein alone at a given light intensity of red light” cannot be determined for reasons cited above. It is unclear whether the structure or the function of the fusion protein is being further limited in claim 47. If the function of the fusion protein is being limited, then just say the Chrimson-tdT fusion protein has a firing rate in RGCs of XXX when exposed to red light. But it is unclear whether the wavelength of red light matters or whether it is dependent upon the structure of the fusion protein. Clarification is required.
Response to arguments
Applicants argue the amendment overcomes the rejections. Applicants’ argument is not persuasive for reasons set forth above.
Claim Rejections - 35 USC § 102
The rejection of claims 26, 30, 32, 35, 37, 38, 43, 44 under 35 U.S.C. 102a1 as being anticipated by Klapoetke (WO 2013071231) has been withdrawn. Klapoetke taught administering a vector encoding a Chrimson protein-fluorescent protein fusion protein to a subject for treating vision loss (pg 42, “Methods of Treating”; pg “Disorders, Diseases, and Conditions”, “methods and light-activated ion channels of the invention may be used for the treatment of visual system disorders, for example to treat vision reduction or loss. A light -activated ion channel of the invention may be administered to a subject who has a vision reduction or loss and the expressed light-activated ion channel can function as light- sensitive cells in the visual system, thereby permitting a gain of visual function in the subject” (lines 27-31). Example 8 (pg 54) and Fig. 7 show the fusion protein is Chrimson-GFP (pg 11, lines 7-10). Pg 51, lines 12-15, discuss an opsin-GFP fusion gene inserted into a vector which is the Chrimson-GFP fusion protein. Pg 56, line 29, describes “delivering the gene encoding the opsin fusion protein into the cells of interest”. The subjects are humans, mice, etc. (pg 38, lines 7-9) which are mammals as required in claim 26. Klapoetke taught injecting the vector intravitreally (pg 44, line 23) and exposing the eye to red light (claims 1, 2, and throughout the examples), e.g. 406 or 660 nm (pg 57, line 6). The treatment described by Klapoetke includes increasing light-sensitive cells (pg 45, line 29, through pg 46, line 7). This is equivalent to administering a vector encoding a Chrimson-fluorescent protein fusion protein to a mammal with photoreceptor degeneration and loss of vision and improving vision as compared to administering a vector encoding Chrimson alone as previously required in claim 26. However, Klapoetke did not teach a Chrimson-tdT fusion protein as newly required in claim 26 (previously in claim 40, now canceled).
Claim Rejections - 35 USC § 103
The rejection of claims 26-30, 32-38, 42-45 are rejected under 35 U.S.C. 103 as being unpatentable over Klapoetke (WO 2013071231) in view of Pan (Annu. Rev. Vis. Sci., 2015, Vol. 1, pg 185-210). Klapoetke and Pan did not teach a Chrimson-tdT fusion protein as newly required in claim 26 (previously in claim 40, now canceled).
The rejection of claims 26, 27, 30-32, 34, 35, 37, 38, 42-44 under 35 U.S.C. 103 as being unpatentable over Klapoetke (WO 2013071231) in view of Bartus (20090202505) has been withdrawn. Klapoetke and Bartus did not teach a Chrimson-tdT fusion protein as newly required in claim 26 (previously in claim 40, now canceled).
The rejection of claims 26, 27, 30-35, 37, 38, 42-44 are rejected under 35 U.S.C. 103 as being unpatentable over Klapoetke (WO 2013071231) in view of Dalkara (Science Translational Med., 2013, Vol. 5, pg 1-11) has been withdrawn. Klapoetke and Dalkara did not teach a Chrimson-tdT fusion protein as newly required in claim 26 (previously in claim 40, now canceled).
Pending and new rejections
A) Claims 26, 30, 32, 35, 37, 38, 40, 43, 44 remain and claims 46-48 are rejected under 35 U.S.C. 103 as being unpatentable over Klapoetke (WO 2013071231) in view of Klapoetke (Nature Med., 2014, Vol. 11, No. 3, pg 338-346).
Klapoetke taught administering a vector encoding a Chrimson protein-fluorescent protein fusion protein to a subject for treating vision loss (pg 42, “Methods of Treating”; pg “Disorders, Diseases, and Conditions”, “methods and light-activated ion channels of the invention may be used for the treatment of visual system disorders, for example to treat vision reduction or loss. A light -activated ion channel of the invention may be administered to a subject who has a vision reduction or loss and the expressed light-activated ion channel can function as light- sensitive cells in the visual system, thereby permitting a gain of visual function in the subject” (lines 27-31). Example 8 (pg 54) and Fig. 7 show the fusion protein is Chrimson-GFP (pg 11, lines 7-10). Pg 51, lines 12-15, discuss an opsin-GFP fusion gene inserted into a vector which is the Chrimson-GFP fusion protein. Pg 56, line 29, describes “delivering the gene encoding the opsin fusion protein into the cells of interest”. The subjects are humans, mice, etc. (pg 38, lines 7-9) which are mammals as required in claim 26. Klapoetke taught injecting the vector intravitreally (pg 44, line 23) and exposing the eye to red light (claims 1, 2, and throughout the examples), e.g. 406 or 660 nm (pg 57, line 6). The treatment described by Klapoetke includes increasing light-sensitive cells (pg 45, line 29, through pg 46, line 7). This is equivalent to administering a vector encoding a Chrimson-fluorescent protein fusion protein to a mammal with photoreceptor degeneration and loss of vision and improving vision as compared to administering a vector encoding Chrimson alone as required in claim 26.
Klapoetke did not teach the fluorescent protein was tdTomato as required in claim 26.
However, Klapoetke (2014) taught a sequence encoding a Chrimson-tdT fusion protein for expression in vivo (pg 2 of Methods, col. 2, 6 lines from the bottom) and using tdT to assist with unbiased selection of opsin-expressing neurons (pg 1 of Methods, col. 2, last full paragraph).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing administer an AAV encoding a Chrimson-fluorescent protein fusion protein to the eye of a mammal to improve vision as described by Klapoetke wherein the fluorescent protein was tdT as described by Klapoetke (2014). Those of ordinary skill in the art at the time of filing would have been motivated to replace the fluorescent protein of Klapoetke with tdT to assist with unbiased selection of opsin-expressing neurons as described by Klapoetke (2014) (pg 1 of Methods, col. 2, last full paragraph)
Claim 30 has been included because Klapoetke taught using Chr88 or ChR (Example 1, “Plasmid construction”; Example 2 ChR.1, ChR2, ChR87, ChrR90; Example 3 ChR88; Example 4, ChR88) which are Chrimson 88 and Chrimson R.
Claim 32 has been included because Klapoetke used an AAV vector (Example 1, pg 48, “Neurons were transfected at 3-5 days in vitro using calcium phosphate (Invitrogen). GFP fluorescence was used to identify successfully transfected neurons. Alternatively, neurons were infected with 0.1-3 μΐ of lent! virus or adeno-associated virus (AAV) per well at 3-5 days in vitro”; Example 14).
Intravitreal injection described by Klapoetke is “to an inner retinal cell” as required in claim 34.
Intravitreal injection described by Klapoetke is the same as claim 35.
Claims 37 and 38 have been included because it is unclear when a protein is “persistent” and because the protocols and reagents described by Klapoetke are the same as those claimed and those described in the specification as being part of the invention; therefore, they inherently MUST result in “persistent” expression of the fusion protein for 2 or 11 months.
The protocols and reagents described by Klapoetke are the same as those claimed and those described in the specification as being part of the invention; therefore, they inherently MUST result in reactivating RGCs as required in claim 42.
Klapoetke taught exposing the eye to red light (claims 1, 2, and throughout the examples) which is 530-640 nm as required in claim 43.
The protocols and reagents described by Klapoetke are the same as those claimed and those described in the specification as being part of the invention; therefore, they inherently MUST result in restoring light sensitivity to the retina as required in claim 44.
Klapoetke taught exposing the eye to red light (claims 1, 2, and throughout the examples) which is 577-598 nm as required in claim 46.
The combined teachings of Klapoetke and Klapoetke taught a fusion protein comprising Chrimson and tdT which inherently MUST have a “firing rate” of 2.34 x 1015 photons.cm2.sec-1 in RGCs as required in claim 47.
The steps and reagents for claim 48 are the exact same ones as those in claim 26 and MUST result in “modulating light induced responses” of RGCs as required in claim 48. Furthermore, claim 48 does not require treating any disease. It only requires activating RGCs which is readily apparent from the combined teachings of Klapoetke and Klapoetke.
Response to arguments
Applicants’ discussion of Klapoetke (WO 2013071231) under anticipation on pg 11-12 of the response is noted but not persuasive. The only limitation in claim 26 or 48 as newly amended that is missing from Klapoetke (WO 2013071231) is tdT.
Applicants’ discussion of Klapoetke (WO 2013071231) and Klapoetke (2014) on pg 19-21 is noted. Applicants appear to argue the amendment overcomes the rejection. It does not for reasons cited above.
Pg 20 says the combined teachings do not disclose “stimulating [an] eye having received” the vector encoding a Chrimson-tdT fusion protein. Applicants’ argument is not persuasive for reasons cited above.
Pg 20-21 says the art discourages combining Chrimson with a fluorescent protein because Asrican (2013) taught a Chrimson-fluorescent fusion protein that had no detectable photocurrency in cells from PV-ChR2-mCherry mice”. Applicants’ argument is not persuasive because Klapoetke (WO 2013071231) taught doing so. Ascrican has a whole chart of mouse lines that express Chrimson-fluorescent fusion proteins. The sentence relied upon by applicants is using 480 nm light which is not red light as required in claims 26 and 48.
B) Claims 26, 28, 29, 30, 32, 33, 34, 35, 36, 37, 38, 40, 43, 44, 45, 46-48 are rejected under 35 U.S.C. 103 as being unpatentable over Klapoetke (WO 2013071231) in view of (Klapoetke, Nature Methods, 2014, Vol. 11, No. 3, pg 343-346, plus Supplementary Materials) and Pan (Annu. Rev. Vis. Sci., 2015, Vol. 1, pg 185-210).
The combined teachings of Klapoetke (WO 2013071231) and Klapoetke (2014) taught administering an AAV vector encoding a Chrimson-tdT fusion protein to a mammal with photoreceptor loss or degeneration and improvement of vision as required in claim 26 for reasons set forth above.
The combined teachings of Klapoetke (WO 2013071231) and Klapoetke (2014) did not teach the mammal had macular degeneration in claims 28 and 45 or retinitis pigmentosa (RP) as required in claim 29.
However, Pan taught treating macular degeneration or retinitis pigmentosa using AAV encoding ChR fused to GFP (pg 188) or AAV2/8 or AAV2/2 encoding ChR2 operably linked to an mGluR6 promoter via subretinal injection (pg 189 “targeting retinal bipolar cells”).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing administer an AAV encoding a Chrimson-fluorescent protein fusion protein to the eye of a mammal to improve vision as described by the combined teachings of Klapoetke (WO 2013071231) and Klapoetke (2014) wherein the mammal had macular degeneration or RP as described by Pan. Those of ordinary skill in the art at the time of filing would have been motivated to apply the method of Klapoetke to patients with macular degeneration or RP to improve their vision.
Claims 30, 32, 35, 37, 38, 40, 43, 44, 46-48 have been included for reasons set forth above.
Claim 33 has been included because Pan taught using AAV2.7m8 (pg 195, fourth row of the table).
Pan taught delivering vectors subretinally (e.g. pg 195, 3rd row of table) for delivery to inner retinal cells as required in claim 34.
Pan taught delivering vectors subretinally (e.g. pg 195, 3rd row of table) as required in claim 36.
The macular degeneration described by Pan is “age-related” as required in claim 45 (pg 186, 1st para).
Thus, Applicants' claimed invention as a whole is prima facie obvious in the absence of evidence to the contrary.
C) Claims 26, 30, 31, 32, 34, 35, 37, 38, 40, 43, 44, 46-48 are rejected under 35 U.S.C. 103 as being unpatentable over Klapoetke (WO 2013071231) in view of Klapoetke (Nature Med., 2014, Vol. 11, No. 3, pg 338-346).
The combined teachings of Klapoetke (WO 2013071231) and Klapoetke (2014) taught administering an AAV vector encoding a Chrimson-tdT fusion protein to a mammal with photoreceptor loss or degeneration and improvement of vision as required in claim 26 for reasons set forth above.
The combined teachings of Klapoetke (WO 2013071231) and Klapoetke (2014) did not teach the sequence encoding the fusion protein was operably linked to a CAG promoter as required in claim 31.
However, Bartus taught injecting a vector encoding a fluorescent protein operably linked to a CAG promoter intravitreally for the rescue of photoreceptors (title,
para 34, Fig. 12).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing administer an AAV encoding a Chrimson-fluorescent protein fusion protein to the eye of a mammal to improve vision as described by the combined teachings of Klapoetke (WO 2013071231) and Klapoetke (2014) wherein the coding sequence was operably linked to a CAG promoter as described by Bartus. Those of ordinary skill in the art at the time of filing would have been motivated to apply the CAG promoter of Bartus to the method of Klapoetke because CAG promoter was well-known for providing high-level transgene expression and because it showed non-specific expression in cells of the inner retina but minimal expression in the outer retina (para 111 of Bartus). Doing so had a reasonable expectation of successfully making/using a vector encoding a fluorescent protein operably linked to a CAG promoter for intravitreal injection as evidenced by Bartus.
Claims 26, 30, 32, 35, 37, 38, 40, 43, 44, 46-48 have been included for reasons set forth above.
Bartus used a CAG or rhodopsin promoter which inherently MUST result in administration to an inner retinal cell as required in claim 34.
Thus, Applicants' claimed invention as a whole is prima facie obvious in the absence of evidence to the contrary.
Claims 26, 30, 32, 35, 37, 38, 40, 41, 43, 44 remain and claims 46-48 are rejected under 35 U.S.C. 103 as being unpatentable over Klapoetke (WO 2013071231) in view of AHH02126.1 (Klapoetke, Nature Methods, 2014, Vol. 11, No. 3, pg 343-346, plus Supplementary Materials) and AFD50641.1 (Ding, Anal Chem., 2011, Vol. 83, No. 24, pg 9687-9693).
The combined teachings of Klapoetke (WO 2013071231) and Klapoetke (2014) taught administering an AAV vector encoding a Chrimson-tdT fusion protein to a mammal with photoreceptor loss or degeneration and improvement of vision as required in claim 26 for reasons set forth above.
Klapoetke did not teach the fusion protein was “Chrimson 88” having the amino acid sequence of SEQ ID NO: 1 fused to a tdT having the amino acid sequence of SEQ ID NO: 3 as encompassed by claim 41.
However, Klapoetke (2014) taught a sequence encoding a Chrimson-tdT fusion protein for expression in vivo (pg 2 of Methods, col. 2, 6 lines from the bottom) and using tdT to assist with unbiased selection of opsin-expressing neurons (pg 1 of Methods, col. 2, last full paragraph).
Klapoetke (2014) taught AHH02126.1
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And Ding taught AFD50641.1:
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Thus, it would have been obvious to those of ordinary skill in the art at the time of filing administer an AAV encoding a Chrimson-fluorescent protein fusion protein to the eye of a mammal to improve vision as described by Klapoetke wherein the fluorescent protein was tdT as described by Klapoetke (2014). Those of ordinary skill in the art at the time of filing would have been motivated to replace the fluorescent protein of Klapoetke with tdT to assist with unbiased selection of opsin-expressing neurons as described by Klapoetke (2014) (pg 1 of Methods, col. 2, last full paragraph). It would have been obvious to use AHH02126.1 described by Klapoetke (2014) and AFD50641.1 described by Ding because Klapoetke (2014) described interchanging proteins in Chrimson and fluorescent fusion proteins (Supplemental Materials). AHH02126.1 is taught by Klapoetke (2014) and AFD50641.1 is an equivalent variant of the tdT described by Klapoetke (2014).
Claims 27, 30, 32, 35, 37, 38, 42-44, 46-48 have been included for reasons set forth above under anticipation.
Response to arguments
Applicants do not specifically address this rejection.
Conclusion
No claim is allowed.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638
