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 on June 11, 2024. Claims 1-17 and 31-33 are currently pending. It is noted that both claim 1 and 31 are independent claims.
Therefore, claims 1-17 and 31-33 are under examination 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.
Information Disclosure Statement
The information disclosure statement (IDS) filed August 14, 2024 has been acknowledged. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
The following claims have been objected to for the following reasons listed:
Claims 10-12 are objected to it recitation of the phrase “before applied” as it is grammatically incorrect. It is advised for the applicant to amend the claims such that it states “before being applied”.
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.
Claims 1-17 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.
Regarding claim 1, it is indefinite in its recitation of the phrase , “optionally followed by contacting said biological sample on said surface with an oxidizing agent”. If "optionally" is being used as exemplary language such as by attempting to further limit a term previously recited, then this can render the claim indefinite.
Regarding claim 6, it is indefinite in its recitation of the term “and/or”. It is unclear if the biological sample contains a biomolecule, cell, cell culture, tissue section, organ, organoid organoculture, AND a whole organism, or just their separate entities. As such, the metes and bounds of the claim are unclear.
Regarding claim 7, it is indefinite in its recitation of “comprises a biomolecule that contains at least a disulfid-bridge, in particular an oxidized thiol-group”. It is unclear if “in particular” is a necessary claim limitation or only exemplary,
Regarding claims 8 and 9, it is indefinite in its recitation of the term “like”. The phrase "like" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 2-17 are indefinite insofar that they depend on claim 1.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 1-8, 10-11, 16 and 32 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Anderson (Pub. No.: WO 9839481 A1. Cited in IDS Filed 04/27/2024).
Regarding claim 1, Anderson teaches a method of mounting a biological sample to a surface, which comprises applying a biological sample to a surface (page 3 lines 13-15, "The present invention relates to a method for immobilizing nucleic acid molecules to solid-phases. More specifically, the present invention describes a method to covalently immobilize 5'-sulfhydryl or 5'-disulfide modified nucleic acid molecules to a solid phase by means of a reversible disulfide bond. ") and contacting the biological sample on said surface with a reducing agent (page 32, “Preferred nucleic acids for use herein are "thiol-modified nucleic acids, " i.e., nucleic acids derivatized to contain at least one reactive thiol moiety. As described in further detail in Example 1 , below, nucleic acids containing at least one reactive thiol are preferably made by treating a nucleic acid containing a 3' or 5' disulfide with a reducing agent, which preferably will not compete in subsequent reactions (i.e. will not react with an iodoacetimido functionality. Disulfide-derivatized nucleic acids can be synthesized according to a variety of methods.”)
Regarding claim 2, Anderson teaches that the surface is glass (page 6, “It would be desirable to have an improved immobilization method that could be used to bind nucleic acid molecules to polystyrene or glass such that their capacity to be used for hybridization, sequencing, or polymorphic analysis would be retained, and which would be rapid, convenient to use, inexpensive, reversible and reusable.”)
Regarding claim 3, Anderson teaches that the surface is hydrophilic (page 32, “The method of claim 13 wherein said polystyrene support is a 96- well microtiter plate containing hydrophilic groups.”)
Regarding claim 4, Anderson teaches that the surface is coated (“page 13, “Because of this feature, it is possible for an aqueous solution to form extremely well defined beads on the surface of incubatedany solid support coated with mercaptosilane”).
Regarding claim 5, Anderson teaches that the surface is a microscopic slide (page 12, “Preferrably, the glass support is a microscope slide, a glass plate, a quart wafer or a silicon wafer.”)
Regarding claim 6, Anderson teaches that the biological sample comprises a biomolecule (page 7, “The present invention provides a method to covalently couple nucleic acid molecules to a solid-phase by means of reversible disulfide bond interactions.”).
Regarding claim 7, Anderson teaches that the biological sample contains a disulfide-bridge (page 7, “In detail, the invention provides a method for coupling a nucleic acid molecule to a solid phase which comprises coupling a sulfhydryl or disulfide modified nucleic acid molecule to a mercaptosilane coated solid-phase.”).
Regarding claim 8, Anderson teaches that the biological sample comprises an extract of biomolecules (“Genomic DNA was isolated using the SDS/Proteinase K procedure (Maniatis, T. Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor (1989)) from peripheral blood nucleated cells of humans or horses enriched from red blood cells by selective lysis accomplished by diluting blood with a threefold volume excess of ACK lysing buffer")
Regarding claim 10, Anderson teaches that the biological sample is incubated in a medium prior to applying to the surface, (pages 23-24, “Hybridization of single-stranded DNA to primers covalently coupled to 96-well plates was accomplished by adding an equal volume of 3M NaCl/50 mM EDTA to the second round asymmetric PCR and incubating each well with 20 μl of this mixture at 55°C for 30 minutes”)
Regarding claims 16 and 32, Anderson teaches that the reducing agent comprises dithiothreitol (page 31, “The method according to claim 6 wherein said reducing agent is dithiothreitol.”).
***
Claim(s) 1, 9, 14-15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Eshghi et al. (Published: 2014. ACS Chemical Biology 9 (9), 2149-2156).
Regarding claim 1, Eshghi teaches a method of mounting a biological sample to a surface, which comprises applying a biological sample to a surface (page 2150 col 2, “In this technique, FFPE tissue sections are mounted on glass slides, which results in immobilization of the tissue glycoproteins on the slides”; page 2155 col 1 “The normal brain tissue sections were mounted on indium tin oxide (ITO) coated glass slides” ) and contacting the biological sample on said surface with a reducing agent (page 2155 col 2, “This was followed by protein denaturing in 40 mM DTT buffer and steaming for 10 min. Pretreatment of the tissue with denaturing reagents improves the deglycosylation significantly” [Note: The contact with the reducing agent, dithiothreitol, was performed after mounting the FFPE to the glass slide, and after the FFPE was deparaffinized]).
Regarding claim 9, Eshghi teaches that the biological sample is tissue (page 2150 col 2, “In this technique, FFPE tissue sections are mounted on glass slides, which results in immobilization of the tissue glycoproteins on the slides”; page 2155 col 1 “The normal brain tissue sections were mounted on indium tin oxide (ITO) coated glass slides” ).
Regarding claim 14, Eshghi teaches that the biological sample comprises a Formalin-Fixed Paraffin-Embedded (FFPE) Tissue (page 2150 col 2, “In this technique, FFPE tissue sections are mounted on glass slides, which results in immobilization of the tissue glycoproteins on the slides”; page 2155 col 1 “The normal brain tissue sections were mounted on indium tin oxide (ITO) coated glass slides” ).
Regarding claim 15, Eshghi teaches that the FFPE tissue is deparaffinized after applied to the surface, (page 2155, col 2, “The FFPE tissue sections were deparaffinized by three xylene washes, 15 min each. Subsequently, they were rehydrated in graded ethanol solutions of 100, 95, 70, and 50% (v/v)”). Note that the deparaffinization is performed after the FFPE tissue is mounted to the slide (See Materials and Methods, Section titled “Mouse Brain Tissue Fixation and Embedding).
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) 1-17 and 31-33 is/are rejected 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))
Regarding claim 1, the teachings of Eshghi render obvious the claimed methodology of claim 1, as iterated above in the 102 rejection the content of which is incorporated herein, in its entirety.
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, Esphigi 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.
***
Claim(s) 1-17 and 31-33 is/are rejected 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).
Regarding claim 1, the teachings of Eshghi render obvious the claimed methodology of claim 1 render obvious the claimed methodology, as iterated above in the 102 rejection the content of which is incorporated herein, in its entirety.
However, the combined teachings of Esghi fail to teach that the tissue sample is cut by a microtome prior to it being applied to a surface, as required by claim 12, and the oxidizing agent required by claims 17, 31 and 33.
Klatt teaches that the tissue sample is cut by a microtome (under Sectioning, “Once the tissues have been embedded, they must be cut into sections that can be placed on a slide. This is done with a microtome. The microtome is nothing more than a knife with a mechanism for advancing a paraffin block standard distances across it. “). Furthermore, Klatt teaches the oxidizing agent to be potassium dichromate (under Fixation – Types of Fixatives, “The purpose of fixation is to preserve tissues permanently in as life-like a state as possible. Fixation should be carried out as soon as possible after removal of the tissues (in the case of surgical pathology) or soon after death (with autopsy) to prevent autolysis… Oxidizing agents include permanganate fixatives (potassium permanganate), dichromate fixatives (potassium dichromate), and osmium tetroxide.”).
It would have been obvious for one with skill in the art to cut the biological sample taught by the teachings of Eshghi, with the microtome taught by Klatt as it was a known histology technique for developing thin slices of specimen for downstream histological analysis at the time of the instant application. Furthermore, it would have been obvious to one with ordinary skill in the art to apply an oxidizing agent to the biological sample in order to preserve the tissues in as life-like a state as possible. 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.
Conclusion
No claims are allowed.
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.
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, 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.
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.
/KATRIEL BARCELLANO KASAYAN/Examiner, Art Unit 1634
/TERESA E KNIGHT/Primary Examiner, Art Unit 1634