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
This action is in response to papers filed June 25, 2026. Currently, claims 1-17 are pending. Claim 1, 6-12, and 15 have been amended, claims 31-33 have been canceled by Applicants’ amendment filed on 6/25/2026. No claims have been added.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a
prior Office action.
Therefore, claims 1-17 are under rejection to which the following grounds of rejection are applicable.
Priority
The instant application claims priority to International Application No. PCT/EP2022/071967, filed on August 4th, 2022. The International Application claims priority to Provisional Application 63/271,392, filed October 25, 2021.
Thus, the earliest possible priority date for the instant application is October 25th, 2021.
Response to Arguments
Withdrawn objections/ Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 112
In view of the Amendments filed June 25, 2026, the rejection of claims 1-17 under 35 USC §112(b) has been withdrawn.
Applicants’ arguments are moot in view of the withdrawn rejection
Claim Rejections - 35 USC § 102
In view of the Amendments filed on June 25, 2026, the rejection of claims 1-8, 10-11, 16 and 32, as being anticipated by Anderson (Pub. No.: WO 9839481 A1. Cite in IDS Filed 04/27/2024) has been withdrawn.
In view of the Amendments filed on June 25, 2026, the rejection of claims 1, 9, 14-15 under 35 U.S.C. 102(a)(1) as being anticipated by Eshghi et al. (Published: 2014. ACS Chemical Biology 9 (9), 2149-2156) has been withdrawn.
Applicants’ arguments are moot in view of the withdrawn rejections.
Claim Rejections - 35 USC § 103
In view of the amendments filed on June 25 2026, the rejection of claims 1-17 and 31-33 under 35 U.S.C. 103 as being unpatentable over Eshghi et al. (Published: 2014. ACS Chemical Biology 9 (9), 2149-2156) in view of Klatt et al. (Published: 2019. "Histotechniques." Utah.ed) has been withdrawn.
In view of the amendments filed on June 25 2026, the rejection of claims 1-17 and 31-33 under 35 U.S.C. 103 as being unpatentable over Eshghi et al. (Published: 2014. ACS Chemical Biology 9 (9), 2149-2156) in view of Zhou et al. (Published: 2017. Lung Section Staining and Microscopy. Bio Protoc. 2017 May 20;7(10)) has been withdrawn.
Applicants’ arguments are moot in view of the withdrawn rejections.
New Objections/Rejections Necessitated by the Amendments filed June 25, 2026
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.
Claim(s) 1-4, 6-11, and 14-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Eshghi et al. (2014. ACS Chemical Biology 9 (9), 2149-2156) (ref. of record), in view of Hoffman et al. (Published: 2016. Curr Protoc Neurosci. 2016 Jul 1;76:2.12.1-2.12.37), as evidenced by Kim et al. ( J Nanosci Nanotechnol. 2015 Nov;15(11):8521-6.). This is a new rejection necessitated by the amendments filed June 25, 2026.
Regarding claim 1, Eshghi teaches a method for preparing and analyzing Formalin-Fixed Paraffin Embedded (FFPE) tissue sections to image N-linked using MALDI Mass Spectrometry (pp. 2149, Abstract). Eshghi achieves this by mounting FFPE tissue on glass slides, which results in the immobilization of tissue glycoproteins (pp. 2150, col 2, para 2). Furthermore, Eshghi prepares the brain tissue by fixing the tissue with formalin, embedding the fixed brain tissues in paraffin, then mounted onto glass slides (pp. 2155, col 1, para 5). Following this, Eshghi denatures the proteins on the tissue by contacting the sample with a reducing agent, dithiothreitol (DTT) (pp. 2155, col 1 para 2).
However, Eshghi does not teach applying an oxidizing agent to the sample.
Hoffman discloses various protocols for preparing tissue to optimize staining for immunocytochemistry techniques (pp. 1, Abstract). Hoffman teaches incubating the tissue in sodium borohydride, a reducing agent that improves fixation (pp. 9, Step 13) followed by incubating the tissue in a hydrogen peroxide solution to remove blood present within the tissue, (pp. 9, Step 14).
It would have been prima facie obvious for a person with ordinary skill in the art to modify the method of Eshghi for treating FFPE tissue, to further comprise the step of treating the tissue with an oxidizing agent such as hydrogen peroxide, as disclosed by Hoffman, with the intention of fully removing the blood from the fixed tissue that has been contacted with DTT. A person with ordinary skill in the art would reasonably expect that the further incubation of tissue in an oxidizing agent would remove excess blood present within the tissue (e.g., brain tissue).
Regarding claim 2, the combined teachings of Eshghi and Hoffman render obvious the claimed method of claim 1. Moreover, Eshghi teaches mounting the tissue onto a glass slide (pp. 2155, col 1, para 5).
Regarding claim 3, the combined teachings of Eshghi and Hoffman render obvious the claimed method of claim 1. Moreover, Eshghi teaches that the surface is a glass slide and that it is coated on indium tin oxide (ITO) coated slides (Eshghi, pp. 2155, col 1, para 5), which are hydrophilic, as evidenced by Kim (Kim, pp. 8521, Abstract).
Regarding claim 4, the combined teachings of Eshghi and Hoffman render obvious the claimed method of claim 1. Moreover, Eshghi teaches that the surface is a glass slide and that it is coated on indium tin oxide (ITO) coated slides (pp. 2155, col 1, para 5).
Regarding claim 5, the combined teachings of Eshghi and Hoffman render obvious the claimed method of claim 1. Moreover, Eshghi teaches that the biological sample originated from mice and are brain tissue samples (pp. 2155, col 1, para 4-5), which is on a microscopic slide.
Regarding claim 6, the combined teachings of Eshghi and Hoffman render obvious the claimed method of claim 1. Moreover, Eshghi teaches that the tissue section originated from mice (pp. 2155, col 1, para 4).
Regarding claim 8, the combined teachings of Eshghi and Hoffman render obvious the claimed method of claim 1. Moreover, Eshghi teaches that the biological sample originated from mice and are brain tissue samples (pp. 2155, col 1, para 4-5).
Regarding claim 9, the combined teachings of Eshghi and Hoffman render obvious the claimed method of claim 1. Moreover, Eshghi teaches that the biological sample originated from mice and are brain tissue samples (pp. 2155, col 1, para 4-5).
Regarding claim 10, the combined teachings of Eshghi and Hoffman render obvious the claimed method of claim 1. Moreover, Eshghi teaches the tissue was incubated in a formalin solution prior to being mounted on a glass slide (pp. 2155, col 1, para 4-5).
Regarding claim 11, the combined teachings of Eshghi and Hoffman render obvious the claimed method of claim 1. Moreover, Eshghi teaches the tissue was incubated in a formalin solution prior to being mounted on a glass slide (pp. 2155, col 1, para 4-5).
Regarding claim 14, the combined teachings of Eshghi and Hoffman render obvious the claimed method of claim 1. Moreover, Eshghi teaches that the biological sample comprises a Formalin-Fixed Paraffin-Embedded (FFPE) Tissue (pp. 2155, col 1, para 4-5).
Regarding claim 15, the combined teachings of Eshghi and Hoffman render obvious the claimed method of claim 1. Moreover, Eshghi teaches that the FFPE tissue is deparaffinized after applied to the surface, (page 2155, col 2, para 2).
Regarding claim 16, the combined teachings of Eshghi and Hoffman render obvious the claimed method of claim 1. Moreover, Eshghi denatures the proteins on the tissue by contacting the sample with a reducing agent, dithiothreitol (DTT) (pp. 2155, col 1 para 2).
Regarding claim 17, the combined teachings of Eshghi and Hoffman render obvious the claimed method of claim 1. Moreover, Hoffman denatures the proteins on the tissue by contacting the sample with an oxidizing agent, hydrogen peroxide (pp. 9, step 15).
***
Claim(s) 1, 5 and 12 are rejected under 35 U.S.C. 103 as being unpatentable Eshghi et al. (2014. ACS Chemical Biology 9 (9), 2149-2156) (ref. of record), in view of Hoffman et al. (Published: 2016. Curr Protoc Neurosci. 2016 Jul 1;76:2.12.1-2.12.37), as evidenced by Kim et al. ( J Nanosci Nanotechnol. 2015 Nov;15(11):8521-6.), as applied to claims 1-4, 6-11, and 14-17, and in further view of Klatt et al. (Published: 2019. “Histotechniques.” Utah.ed) (ref. of record). This is a new rejection necessitated by the amendments filed June 25, 2026.
With regard to claim 1, the combined teachings of Eshghi, Hoffman, and Kim render obvious the claimed methodology of claim 1. Moreover, Eshghi et al. teaches that fixed paraffin-embedded (FFPE) tissue sections are mounted in a glass slide (page 2150; col 2, par. 2)
However, the combined teachings fail to explicitly disclose the use of a microscope slide.
Klatt discloses that tissues can be prepared on microscope slides to be viewed under the microscope (pp. 1).
It would have been obvious for a person with ordinary skill in art to specifically use a microscopic glass slide to prepare tissue sections when mounting a biological specimen onto a glass slide, as taught by Eshghi, TO have additional examination of a tissue under the microscope. Further, using a microscope slide to mount biopsied tissue was a technique known in the art prior to the effective filing date. There would have been reasonable expectations of success in combining these teachings as one of ordinary skill in the art would recognize to combine known elements in the art to give predictable results
Regarding claim 12, the combined teachings of Eshghi, Hoffman, Kim and Klatt render obvious the claimed method of claim 1. Moreover, Klatt teaches that tissues can be cut into sections that are only 6 to 8 microns thick, then picked up on a glass slide (under Sectioning, pp. 3), rendering obvious Eshghi’s tissue section
***
Claim(s) 1 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Eshghi et al. (2014. ACS Chemical Biology 9 (9), 2149-2156) (ref. of record), in view of Hoffman et al. (Published: 2016. Curr Protoc Neurosci. 2016 Jul 1;76:2.12.1-2.12.37), as evidenced by Kim et al. ( J Nanosci Nanotechnol. 2015 Nov;15(11):8521-6.), as applied to claims 1-4, 6-11, and 14-17, and in further view of Zhou et al. (Published: 2017. Lung Section Staining and Microscopy. Bio Protoc. 2017 May 20;7(10)) (ref. of record). This is a new rejection necessitated by the amendments filed June 25, 2026.
With regard to claim 1, the combined teachings of Eshghi, Hoffman, and Kim render obvious the claimed methodology of claim 1.
However, Eshghi fails to teach that the tissue is lung or skin tissue. Moreover, Eshghi teaches that DTT is utilized to denature proteins (page 2155, col 2, “To denature proteins on tissue slides…This was followed by protein denaturing in 40 mM DTT buffer and steaming for 10 min. “).
Zhou et al teaches that the lung tissue was fixed and embedded, then mounted on glass slides (page 4, “Lungs are fixed and embedded in paraffin as described in Baligar et al. (2016). Lung sections shall be cut at 4-5 µm from paraffin embedded lung tissues, and mounted on glass slides.”). Furthermore, they are deparaffinized for downstream analysis, (page 4, “Deparaffinize the sections by two successive xylene baths, 10 min each.”). Zhou also teaches that the preparation for the FFPE tissue uses lung tissue (“Lungs are fixed and embedded in paraffin as described in Baligar et al. (2016). Lung sections shall be cut at 4-5 µm from paraffin embedded lung tissues, and mounted on glass slides.”).
It would have been obvious to substitute brain tissue taught in Eshghi with the lung tissue described in Zhou as it was well established at the time of the claimed method that FFPE preparation could be routinely applied to various tissue types, including lung tissue. Furthermore, Eshghi does not indicate that the use of the reducing agent is limited to only brain tissue, and broadly states the use of DTT is to denature protein. There would have been reasonable expectations of success in combining these teachings as one of ordinary skill in the art would recognize to combine known elements in the art to give predictable results.
Response to Arguments as they apply to Eshghi et al., Zhou et al. and Klatt et al.
Beginning on page 5 of the Remarks filed on June 25, 2026, Applicants’ essentially argue the following:
Compared to claim 1 it is acknowledged that DTT is a reducing agent, however, Eshghi did not follow DTT treatment with exposure to an oxidizing agent. Since Eshghi does not teach each element as provided in claim 1, the claims are not anticipated by Eshghi.
Zhou does not contact the lung tissue with a reducing agent followed by exposure to an oxidizing agent. Thus, the addition of Zhou fails to correct the deficiency of the rejection over Eshghi at least as amended.
Klatt only broadly teaches using oxidizing agents to fix tissue. It would have not been obvious to treat Eshghi’s sample with an oxidizing agent after denaturing protein.
Applicant's arguments have been fully considered but they are not persuasive for the following
reason(s):
Regarding 1), to the extent that Eshghi did not teach exposure to an oxidizing agent, the Examiner agrees. However, Hoffman et al. is relied upon to remedy the deficiencies of Eshghi. Specifically, Hoffman teaches incubating the tissue in sodium borohydride, a reducing agent that improves fixation (pp. 9, Step 13) followed by incubating the tissue in a hydrogen peroxide solution to remove blood present within the tissue, (pp. 9, Step 14). Furthermore, Hoffman discloses that fixing the tissue does not eliminate all endogenous peroxidases present in fresh tissue in macrophages and blood cells and relies on hydrogen peroxide to neutralize it and avoid the emergence of background noise for downstream analysis using immunocytochemistry (pp. 16, step 10). Therefore, a person with ordinary skill in the art would have been motivated to apply an oxidizing agent after the reducing agent to further remove the excess blood from the brain tissue of Eshghi and decrease background noise of the sample when using it for downstream analysis.
Regarding 2) to the extent that Eshghi and Zhou did not teach exposure to an oxidizing agent, the Examiner agrees. However, Hoffman remedies the deficiencies of claim 1, as described above. Moreover, Zhou is not relied upon teaching all the limitations of claim 1, specifically for failing to teach that the lung tissue is denatured with DTT. Zhou is relied upon because it provides a similar method of mounting FFPE lung tissue onto a glass slide, as it was well established at the time of the claimed method that FFPE preparation could be routinely applied to various tissue types, including lung tissue. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Regarding 3), to the extent that Eshghi and Zhou did not teach exposure to an oxidizing agent, the Examiner agrees. However, Hoffman remedies the deficiencies of claim 1, as described above. Further, Klatt is relied upon for displaying that tissue can be mounted onto microscopic glass slides to allow the examination of tissue under a microscope, or other forms of microscopy. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Conclusion
No claim allowed.
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 Katriel B Kasayan whose telephone number is (571)272-1402. The examiner can normally be reached 10-4p.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G Leavitt can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATRIEL BARCELLANO KASAYAN/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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