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 .
Claim 100 has been added.
Claims 1-2, 17-18, 23, 28-29, 34 and 98-100 are pending.
Claims 3-16, 19-22, 24-27, 30-33, and 35-97 are cancelled.
Claims 1 is amended.
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn. The following rejections or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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, 17, 18, 23, 28, 29, 34 and 98-99 are rejected under 35 U.S.C. 103 as being unpatentable over EARLY (An automated high-resolution in vivo screen in zebrafish to identify chemical regulators of myelination. eLife. 2018.) in view of GONZALEZ-FERNANDEZ (Novel strategy for subretinal delivery in Xenopus. Molecular Vision. 2011).
Regarding claim 1, EARLY teaches a method of in vivo screening of compounds in zebrafish (abstract) that comprises: administering compounds to a zebrafish embryo (page 2, paragraph 3) via exposing the embryos to a target compound, diluted with water, in well plates (Page 8, paragraph 1), which reads on the first part of step A administering a candidate substance to an embryo of an animal (excluding human).
The embryos were examined for the amount of differentiated cells in the spinal cord before administration of an active compound (Page 5, paragraph 3), which reads on step C obtaining a measurement of an amount of differentiated cells of the specific tissue in the animal that has undergone step A.
The embryos were then administered SKP2-25 and examined again to determine the increase of differentiated cells (Page 5, paragraph 3 and page 6, paragraph 1), which reads on step D as the active ingredient, or a candidate substance that increases the amount of differentiated cells of the specific tissue measured in step C, as compared with a case where the candidate substance is not administered.
The spine was examined after administration to see the effect of the test substance (figure 2 and 3), which reads on the specific tissue the region develops into is a same tissue as the specific tissue the amount of differentiated cells is obtained for in step C.
Note, the limitation in claim 1 of wherein the active ingredients are for the treatment or prevention of a disease, disorder, or illness of a nervous system, or symptoms thereof, caused by damage or functional decline of the nervous system is inherent since all active steps within the claim are met. Furthermore, EARLY teaches multiple active ingredients were examined including Apicidin, which is a HDAC inhibitor (table 2). Since HDAC inhibiters are defined in claim 34 as a candidate substance being screened, it would be inherent that the active ingredients are for the treatment or prevention of a disease, disorder, or illness of a nervous system, or symptoms thereof, caused by damage or functional decline of the nervous system is inherent since the same candidate substance is being screened in the prior art.
Regarding claim 17, zebrafish were examined (abstract).
Regarding claims 18 and 98, the purpose of the study was to examine cells that affect the nervous system and cause diseases and determine therapeutic treatments for such diseases (abstract).
Regarding claims 23 and 29, a fluorescent reporter was used to determine the amount of cells in specific areas (Page 3, paragraph 4 and page 5 paragraph 1) and the differentiated cells were measured using 2D maxima identification tool (Page 5, paragraph 2).
Regarding claim 34, multiple active ingredients were examined including Apicidin, which is a HDAC inhibitor (table 2).
Additional disclosure: CI-994 was screened using the method (Supplemental table 1).
EARLY does not teach the specific form of administration of the active ingredient, such as injecting into a specific site on the embryo, such as the optic vesicle.
Regarding claim 1, GONZALEZ-FERNANDEZ teaches a method of injecting an active agent specifically into the optic vesicle of embryos using a micromanipulator (abstract). This method was less invasive/traumatic to the embryos being studied (page 2957, paragraph 4) and allowed for the eye to specifically be studied as it forms after injection (page 2957, paragraph 5).
Regarding claim 99, GONZALEZ-FERNANDEZ teaches a method of injecting an active agent specifically into the optic vesicle of embryos using a micromanipulator (abstract).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate injecting into a specific site on the embryo, such as the optic vesicle. The person of ordinary skill in the art would have been motivated to make those modifications, because the method is less invasive/traumatic and allowed for the eye to be specifically studied after the local injection to the eye, and reasonably would have expected success because the references are in the same field of endeavor, such as administering an active agent to an embryo for the purpose of studying the effects. Furthermore, it is the eye and the spine are functional equivalents of areas to be examined in an embryo.
Claims 1, 2, 17, 18, 23, 28, 29, 34 and 98-99 are rejected under 35 U.S.C. 103 as being unpatentable over EARLY (An automated high-resolution in vivo screen in zebrafish to identify chemical regulators of myelination. eLife. 2018.) and GONZALEZ-FERNANDEZ (Novel strategy for subretinal delivery in Xenopus. Molecular Vision. 2011) in view of ZHANG (Class I histone deacetylase (HDAC) inhibitor CI-994 promotes functional recovery following spinal cord injury. Cell Death and Disease. 2018.).
EARLY and GONZALEZ-FERNANDEZ teach Applicant’s invention as discussed above.
EARLY and GONZALEZ-FERNANDEZ do not specifically teach that CI-994 is used as a treatment for spinal cord injuries.
Regarding claim 2, ZHANG teaches that HDAC inhibitors, such as CI-994 are used as treatment for spinal cord injuries (abstract).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate screening for an active ingredient for the treatment of a spinal cord injury. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success, because EARLY screens for CI-994 and CI-994 is a treatment for a spinal cord injury.
Claims 1, 2, 17, 18, 23, 28, 29, 34 and 98-100 are rejected under 35 U.S.C. 103 as being unpatentable over EARLY (An automated high-resolution in vivo screen in zebrafish to identify chemical regulators of myelination. eLife. 2018.), GONZALEZ-FERNANDEZ (Novel strategy for subretinal delivery in Xenopus. Molecular Vision. 2011) and ZHANG (Class I histone deacetylase (HDAC) inhibitor CI-994 promotes functional recovery following spinal cord injury. Cell Death and Disease. 2018.) in view of CHEN (Self-renewal of embryonic stem cells by a small molecule. PNAS. 2006.).
EARLY, GONZALEZ-FERNANDEZ and ZHANG teach Applicant’s invention as discussed above.
EARLY, GONZALEZ-FERNANDEZ and ZHANG do not teach examining undifferentiated cells or administering a substance that increases undifferentiated cells.
CHEN teaches a method that administers a test substance that propagates undifferentiated cells (abstract), which means it is a substance that multiplies/increases differentiated cells upon administration. The method involved undifferentiated cells whose growth was measured upon administration of the test substance (figure 1, specifically 1A and 1C).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate examining undifferentiated cells and administering a substance that increases undifferentiated cells. The person of ordinary skill in the art would have been motivated to make those modifications, because it would allow the method in EARLY to be utilized for a different substance with a different effect, so that it can have purpose for many different substances, and reasonably would have expected success because EARLY’s method is towards administering a substance to cells and then measuring the effect on the cells.
Response to Arguments
Applicant argues, Early does not teach local injection combined with measurement of specific tissue in the region of the local injection as in the steps of claim 1. Gonzalez-Fernandez is relied on for injection into an optic vesicle of an embryo for studies of the eye. However, Early is specifically directed to high-throughput analysis of embryos developed in wells to which treatment is applied (Early at pages 4, 5, 8, and 23-24). In contrast, the injection as taught by Gonzalez-Fernandez requires each embryo be individually placed in a particular orientation within modeling clay and manipulating a flap of clay to secure the embryo (Gonzalez-Fernandez at page 2959). The precise and mechanically intensive nature of the injections of Gonzalez-Fernandez would frustrate the purpose of Early to achieve high throughput through the well-based administration of compounds and subsequent processing of samples. The proposed combination would require replacing the core administration format of Early with an individual micromanipulation procedure, thereby destroying the high-throughput advantage for which Early's system was designed. Persons having ordinary skill in the art thus practically could not combine Early and Gonzalez-Fernandez in the manner proposed by the rejection while retaining the advantageous properties of screening method taught by Early.
The examiner does not find the argument persuasive because as discussed above, it would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate injecting into a specific site on the embryo, such as the optic vesicle. The person of ordinary skill in the art would have been motivated to make those modifications, because the method is less invasive/traumatic and allowed for the eye to be specifically studied after the local injection to the eye, and reasonably would have expected success because the references are in the same field of endeavor, such as administering an active agent to an embryo.
As stated, this combination would provide an advantage, such as allowing a specific region to be examined to determine effects.
Applicant argues, Gonzalez-Fernandez is a technique for targeted delivery to ocular structures in
Xenopus for localized eye/retina studies after injection. The injection in Gonzalez-Fernandez is based on how connections among spaces within the Xenopus embryo change over time to sequester the injected material within a target space (Gonzalez-Fernandez at page 2957). In contrast, the present claims deliberately tie the injection to a region to the future tissue to be measured itself, based on the developmental correspondence of the region to the specific tissue being measured. Gonzalez-Fernandez, even if combined with Early, does not teach or suggest using the developmental relationship of region and tissue as in claim 1, which recites that the specific tissue the region develops into is a same tissue as the specific tissue the amount of undifferentiated cells is obtained for in step B and/or the amount of differentiated cells is obtained for in step C.
The examiner does not find the argument persuasive because as discussed above, EARLY teaches that the embryos were examined for the amount of differentiated cells in the spinal cord before administration of an active compound (Page 5, paragraph 3) and that the spine was examined after administration to see the effect of the test substance (figure 2 and 3), which reads on the specific tissue the region develops into is a same tissue as the specific tissue the amount of differentiated cells is obtained for in step C.
GONZALEZ-FERNANDEZ is cited to show injecting locally can be used an alternative to provide an advantage, such as allowing a specific region to be examined to determine effects.
Applicant argues, In Early, compounds are administered to zebrafish embryos in wells, and no specific sites are treated. Accordingly, Early does not teach or suggest administration of compounds specifically to at least one selected from the group consisting of a neural plate forming a predetermined region at a gastrulation stage, a neural plate, a neural tube, a predetermined region of a brain in front of the neural tube, a predetermined region of a spinal cord behind the neural tube, a primary brain vesicle, a lumen of the primary brain vesicle, a secondary brain vesicle, a lumen of the secondary brain vesicle, and an optic vesicle as in claim 99. Gonzalez-Fernandez does not remedy this deficiency. While Gonzalez-Fernandez discloses injection into the optic vesicle of a xenopus, that disclosure is a specific ocular delivery technique for localized eye/retina studies. The specific delivery of Gonzalez-Fernandez
does not provide a reason to modify Early's high-throughput zebrafish myelination screen to locally inject candidate substances into any of the neural developmental regions recited in claim 99, let alone further measuring undifferentiated cells and/or differentiated cells of the specific tissue into which the injected region develops. Gonzalez-Fernandez therefore does not teach or suggest the claimed screening method, and does not render claim 99 obvious in combination with Early.
The examiner does not find the argument persuasive because as discussed above, it would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate injecting into a specific site on the embryo, such as the optic vesicle. The person of ordinary skill in the art would have been motivated to make those modifications, because the method is less invasive/traumatic and allowed for the eye to be specifically studied after the local injection to the eye, and reasonably would have expected success because the references are in the same field of endeavor, such as administering an active agent to an embryo.
As stated, this combination would provide an advantage, such as allowing a specific region to be examined to determine effects.
Additionally EARLY teaches that the embryos were examined for the amount of differentiated cells in the spinal cord before administration of an active compound (Page 5, paragraph 3) and that the spine was examined after administration to see the effect of the test substance (figure 2 and 3), which reads on the specific tissue the region develops into is a same tissue as the specific tissue the amount of differentiated cells is obtained for in step C.
Applicant argues, The cited art does not teach or suggest a method requiring Step B of obtaining a measurement of an amount of undifferentiated cells of the specific tissue into which the locally injected region develops. Early detects myelinating oligodendrocytes, which are a differentiated cell, and Gonzalez-Fernandes does not provide any teachings regarding measurement of amounts of undifferentiated cells. Accordingly, Gonzalez-Fernandez does not remedy the deficiencies of Early, and new claim 100 is not taught or suggested by the combination thereof.
The examiner does not find the argument persuasive because as discussed above, CHEN teaches a method that administers a test substance that propagates undifferentiated cells (abstract), which means it is a substance that multiplies/increases differentiated cells upon administration. The method involved undifferentiated cells whose growth was measured upon administration of the test substance (figure 1, specifically 1A and 1C).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate examining undifferentiated cells and administering a substance that increases undifferentiated cells. The person of ordinary skill in the art would have been motivated to make those modifications, because it would allow the method in EARLY to be utilized for a different substance with a different effect, so that it can have purpose for many different substances, and reasonably would have expected success because EARLY’s method is towards administering a substance to cells and then measuring the effect on the cells.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 SAMANTHA L. MEJIAS whose telephone number is (703)756-5666. The examiner can normally be reached M-F.
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/S.L.M./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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