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 .
DETAILED ACTION
Responsive to communications entered 10SEP2025
Claims pending 1-15
Claims currently under consideration 1-15
Priority
This application has a filing date of 02/16/2022 and is a 371 of
PCT/JP2020/031840 08/24/2020.
Acknowledgment is made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d) to JAPAN 2019-157984 08/30/2019 and JAPAN 2020-047552 03/18/2020. Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
Withdrawn Objection(s) and/or Rejection(s)
The rejection of claims 4 and 13 under 35 U.S.C. 112 second paragraph is hereby withdrawn in light of Applicant’s amendments.
Maintained 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 1-3,6,8,10,14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by the iDISCO+ protocol dated December 2016 (IDS entry 2/16/2022; referred to hereafter as DISCO; of record).
As in claims 1,2,3,10, DISCO (an acronym for three-Dimensional Imaging of Solvent-Cleared Organs) discloses throughout the document and especially the first two pages, a blocking solution that includes: greater than 1 percent TritonX-100 (a nonionic surfactant), greater 200 millimolar phosphate buffered saline (PBS, a neutral buffer), and donkey serum as a blocking reagent; a concentrated wash solution (PTwH) that has Tween-20 as a nonionic surfactant at a concentration higher than 1 percent and PBS at not less than 200 millimolar. Like claims 6,8,12 (in part) and 14, DISCO teaches an antibody for immunostaining biological organs such as brains (that lack fat) or tissue sections.
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Please note that the above rejection has been updated from the original version to more clearly address applicants’ newly amended and/or added claims and/or arguments.
Response to Arguments
Referring to DISCO as iDisco, the remarks accompanying the present response argue not all elements are taught in claims 8-11 and 12-14. More particularly the pertinent section starting with the last paragraph at p 6 to p 7, contends the reference does not teach a non-ionic surfactant concentration greater than 1 %, nor salt concentration greater than 200 millimolar because
The examiner respectfully disagrees. Applicant’s arguments have been fully considered but they are not deemed persuasive for the following reasons.
First of all, claims 9,11 nor 12-13 have been rejected for anticipation.
The remarks contend buffer PTx.2 and PTwH in DISCO are both diluted ten fold, thus the TritonX-100 is 0.2 %, Tween-20 is 0.2 % and PBS (NaCl salt) is 137 millimolar.
This is not found persuasive because the arguments of counsel cannot take the place of evidence in the record. In re Schulze,346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) (“An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness.”) (see MPEP 2145 I.) In the instant case, Applicant’s counsel argues buffers PTx.2 and PTwH in the DISCO reference are diluted, however counsel does not provide objective evidence establishing this as a fact. Alas, even assuming arguendo that said buffers were diluted, this does not change the fact that concentrated PTx.2 (e.g. before adding more water) has1.9 % v/v Triton-X100, concentrated PTwH has 1.9 % v/v Tween-20 and both have 1.3 molar salt are expressly disclosed therein DISCO.
Maintained 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.
Claims 1-3,6,8,10,14 and 5,7,9,11,12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by DISCO in view of Kemp et al (US AppPub 20150225713)
DISCO is relied on as above.
DISCO does not explicitly teach: a dye of claims 5 & 7; a slightly acidic buffer of claims 9 and 12; nor phase separation reagent of claim 11.
As in claims 5,7,9,11 and 12, Kemp et al teach throughout the document and especially the abstract and paragraphs 0021,0037 plus document claim 35, phase separation reagents in a slightly acidic buffer and an optional dye that may be used to capture nucleic acids (e.g. DNA) from samples.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have captured nucleic acids in the manner of Kemp et al from tissues as in DISCO.
One of ordinary skill in the art would have been motivated to have captured nucleic acids in the manner of Kemp et al from tissues as in DISCO for the advantage of quickly, reliably and efficiently providing DNA or RNA for downstream applications like PCR, restriction digestions, sequencing, etc., all benefits as suggested by Kemp et al in paragraph 0008 and 0039.
One of ordinary skill in the art would have had a reasonable expectation of success in extracting nucleic acids from tissue samples as in DISCO using Kemp’s methodology, since just such an application indicated as suitable in Kemp paragraph 0080.
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Please note that the above rejection has been updated from the original version to more clearly address applicants’ newly amended and/or added claims and/or arguments.
Response to Arguments
The remarks accompanying the present response argue motivation is lacking because Kemp is unrelated to biological tissue staining and the examiner is using hindsight.
Applicant’s arguments have been fully considered but they are not deemed persuasive for the following reasons.
In response to applicant's argument that Kemp et al is nonanalogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, Kemp et al is deemed reasonably pertinent is so far as it is of interest to extract DNA from the same immunohistological tissue sample for relating genotype to phenotype.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Here, motivation to combine the DISCO protocol with Kemp et al comes from the prior art of Kemp itself, nothing from Applicant’s application so reconstruction is proper.
Beyond that, Applicant does not offer further arguments regarding the above obviousness rejection(s) beyond what was set forth with regard to the 35 U.S.C. § 102 rejection, above. To the extent that Applicant is merely repeating their previous argument, the examiner respectfully submits that those issues were adequately addressed in the above section(s), which is/are incorporated in their entireties herein by reference.
New Claim Rejection(s) – 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.
Claims 1-3,6,8,10,14 and 4,13,15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by DISCO (of record) in view of Aoki et al (1997 J. Histochemistry & Cytochemistry 45:875-81) as evidenced by Ertruk et al (2014 J. Visualized Experiments 89 at e51382; ten pages) and Hawkes et al (1982 Analytical Biochemistry 119:142-7) if necessary
DISCO is relied on as in the anticipation rejection above.
DISCO does not explicitly teach a dye or a compound of general formula I that is substituted with a nitrogen atom of claims 4,13 and 15.
Aoki et al teach throughout the document and especially figures 1, 3, and the first paragraph at p 876, antibodies that bind citrulline. Citrulline constitutes a compound of general formula I when R3=R4=R2=H and R1 is a nitrogen substituted carboxylic acid, reading on claims 4 and 13. Using Hawke’s procedure that includes a 4-chloro-1-naphthol dye (cf Hawkes et al p 144) and like claims 4,13 and 15, Aoki et al therefore suggests exposing a biological tissue to a biological tissue-staining reagent, the reagent comprising a dye, an immunostaining antibody and citrulline in situ.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized DISCO imaging to supplement the traditional histological tissue section as in Aoki et al
One of ordinary skill in the art would have been motivated to have utilized DISCO imaging to supplement the traditional histological tissue section as in Aoki et al because rendering an entire organ transparent allows for examination of an entire 3D specimen as opposed to one plane, is more informative as noted by Ertruk et al on the first page.
One of ordinary skill in the art would have had a reasonable expectation of success in rendering an entire organ transparent with DISCO for imaging with Aoki’s citrulline antibodies in light of the impressive results reported by Ertruk in figures 1-8.
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 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.
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 CHRISTOPHER M GROSS whose telephone number is (571)272-4446. The examiner can normally be reached M-F 10-6.
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, Heather Calamita can be reached on (571)272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHRISTOPHER M GROSS/
Primary Examiner, Art Unit 1684
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