DETAILED ACTION
Response to Amendment
Applicant’s response to the office action filed on December 17, 2025 has been entered. The claims pending in this application are claims 1-3, 5, 7, 13-15, 18, 20, 22, 26, 28, 37, 45, 49-51, 54, 67, 68, 70, 73, 75-77, 79, 85, and 86 wherein claims 49-51, 54, 67, 68, 70, 73, 75-77, 79, 85, and 86 have been withdrawn due to the restriction requirement in the office action mailed on June 18, 2025. The objections and rejections not reiterated from the previous office action are hereby withdrawn in view of applicant’s amendment filed on December 17, 2025. Claims 1-3, 5, 7, 13-15, 18, 20, 22, 26, 28, 37, and 45 will be examined.
Claim Objections
Claim 1 is objected to because of the following informality: “the biological sample” in step (d) should be “the biological sample in the first three-dimensional polymerized matrix”. 44
Claim 2 is objected to because of the following informality: “delivering the first polymerizable matrix-forming material to the biological sample” should be “said delivering the first polymerizable matrix-forming material to the biological sample”.
Claim 5 or 7 or 13 is objected to because of the following informality: “immobilizing the biological sample embedded in the first three-dimensional polymerized matrix to the second substrate” should be “said immobilizing the biological sample embedded in the first three-dimensional polymerized matrix to the second substrate”.
Claim 18 is objected to because of the following informality: “attachment” in line 5 should be “the attachment”.
Claim 28 is objected to because of the following informality: “the immobilizing” should be “the immobilizing step”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
New Matter
Claims 1-3, 5, 7, 13-15, 18, 20, 22, 26, 28, 37, and 45 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 limitations “delivering a first polymerizable matrix-forming material to a biological sample immobilized on a first substrate” and “delivering a second polymerizable matrix-forming material to a biological sample immobilized on a second substrate” are added to steps (a) and (c) of independent claim 1 respectively. Although the specification describes that three-dimensional polymerized matrices can be hydrogels (see paragraphs [0007] and [0033] of US 2023/0013775 A1, which is US application of this instant application), nowhere in the specification describes such limitations recited in claim 1 since the specification does not describe phrases “a first polymerizable matrix-forming material” and “a second polymerizable matrix-forming material” and there is no definition for “polymerizable matrix-forming material” in the specification and art. Although the closest definition in the art related to “polymerizable matrix-forming material” is “polymer matrix” which is the continuous phase of composite materials, in which polymer chains serve as the backbone or host for reinforcing materials such as fibers or particles, polymers are macromolecules composed of many repeating units (monomers) which can be natural (e.g., cellulose in wood) or synthetic (e.g., polyethylene in plastic bags) and include thermosetting polymers, thermoplastic polymers and elastomers, and matrix, in this context, refers to the medium in which the reinforcement is embedded (see “Understanding the Polymer Matrix: A Comprehensive Guide”) and the specification describes that polymer matrix can be hydrogel matrix (see paragraph [0008] of US 2023/0013775 A1, which is US application of this instant application), nowhere in the specification describes that a polymer matrix is a thermoplastic matrix or an elastomer matrix. Furthermore, in applicant’s remarks filed on December 17, 2025, applicant does not indicate which parts in the specification support above claim limitations recited in claim 1.
MPEP 2163.06 notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).” MPEP 2163.02 teaches that “Whenever the issue arises, the fundamental factual inquiry is whether a claim defines an invention that is clearly conveyed to those skilled in the art at the time the application was filed...If a claim is amended to include subject matter, limitations, or terminology not present in the application as filed, involving a departure from, addition to, or deletion from the disclosure of the application as filed, the examiner should conclude that the claimed subject matter is not described in that application.” MPEP 2163.06 further notes “When an amendment is filed in reply to an objection or rejection based on 35 U.S.C. 112, first paragraph, a study of the entire application is often necessary to determine whether or not “new matter” is involved. Applicant should therefore specifically point out the support for any amendments made to the disclosure” (emphasis added).
Scope of Enablement
This rejection is modified from but different from the scope of enablement rejection mailed on June 18, 2025.
Claims 1-3, 5, 7, 13-15, 18, 20, 22, 26, 28, 37, and 45 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 forming a first three-dimensional polymerized matrix embedding a biological sample using a first hydrogel monomer and forming a second three-dimensional polymerized matrix embedding the biological sample using a second hydrogel monomer, does not reasonably provide enablement for forming a first three-dimensional polymerized matrix embedding a biological sample using any kind of first polymerizable matrix-forming material and forming a second three-dimensional polymerized matrix embedding the biological sample using any kind of second polymerizable matrix-forming material as recited in claims 1-3, 5, 7, 13-15, 18, 20, 22, 26, 28, 37, and 45. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
The Nature of The Invention
The claims are drawn to a method for processing a biological sample. The invention is a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The Breadth of The Claims
Claims 1-3, 5, 7, 13-15, 18, 20, 22, 26, 28, 37, and 45 encompass a method for processing a biological sample, comprising: a) delivering any kind of first polymerizable matrix-forming material to a biological sample immobilized on a first substrate; b) forming a first three-dimensional polymerized matrix from the first polymerizable matrix-forming material, thereby embedding the biological sample in the first three-dimensional polymerized matrix; c) immobilizing the biological sample embedded in the first three-dimensional polymerized matrix to a second substrate; d) delivering any kind of polymerizable second matrix-forming material to the biological sample immobilized on the second substrate; and e) forming a second three-dimensional polymerized matrix from the second polymerizable matrix-forming material, thereby embedding the biological sample in the second three-dimensional polymerized matrix.
Working Examples
The specification provides 2 examples (see pages 40 and 41 of US 2023/0013775 A1, which is US publication of this instant case). However, the specification provides no working example for forming a first three-dimensional polymerized matrix embedding a biological sample using any kind of first polymerizable matrix-forming material and forming a second three-dimensional polymerized matrix embedding the biological sample using any kind of second polymerizable matrix-forming material as recited in claims 1-3, 5, 7, 13-15, 18, 20, 22, 26, 28, 37, and 45.
The Amount of Direction or Guidance Provided and The State of The Prior Art
Although the specification provides 2 examples (see pages 40 and 41 of US 2023/0013775 A1, which is US publication of this instant case), the specification provides no working example for forming a first three-dimensional polymerized matrix embedding a biological sample using any kind of first polymerizable matrix-forming material and forming a second three-dimensional polymerized matrix embedding the biological sample using any kind of polymerizable second matrix-forming material as recited in claims 1-3, 5, 7, 13-15, 18, 20, 22, 26, 28, 37, and 45. Furthermore, there is no experimental condition and/or experimental data in the specification to support the claimed invention. During the process of the prior art search, the examiner has not found any prior art which is related to form a first three-dimensional polymerized matrix embedding a biological sample using any kind of first polymerizable matrix-forming material and form a second three-dimensional polymerized matrix embedding the biological sample using any kind of second polymerizable matrix-forming material as recited in claims 1-3, 5, 7, 13-15, 18, 20, 22, 26, 28, 37, and 45.
Level of Skill in The Art, The Unpredictability of The Art, and The Quantity of Experimentation Necessary
While the relative skill in the art is very high (the Ph.D. degree with laboratory experience), there is no predictability whether a first three-dimensional polymerized matrix embedding a biological sample can be formed using any kind of first polymerizable matrix-forming material and a second three-dimensional polymerized matrix embedding the biological sample can be formed using any kind of second polymerizable matrix-forming material as recited in claims 1-3, 5, 7, 13-15, 18, 20, 22, 26, 28, 37, and 45.
Since the specification teaches that “[S]tarting with a tissue section sample already immobilized on an initial slide (slide A), the sample is fixed and permeabilized. A first specialized hydrogel mixture (hydrogel mixture A) is added to the tissue sample and polymerized such that the tissue sample is embedded in the hydrogel matrix formed from hydrogel mixture A. The hydrogel mixture A can contain hydrogel monomers, such as polyacrylamide, cellulose, alginate, polyamide, cross-linked agarose, cross-linked dextran or cross-linked polyethylene glycol. The hydrogel can also optionally contain stimulus-responsive monomers (e.g., acrylic acid and acrylamide monomers, or N-isopropylacrylamide and acrylamide monomers, which can expand upon exposure to the appropriate stimulus and the expansion of which can facilitate detachment from the initial slide, and/or cross-linking agents suitable for forming covalent bonds between the biological sample and the hydrogel matrix (e.g., N,N,N’,N’-tetramethylethylenediamine (TEMED), N,N-methylenebisacrylamide (BIS), or N,N’-diallyltartardiamide (DATD))”, “[T]he embedded sample is then cleared with a suitable clearing agent, such as a detergent, digestion enzyme (e.g., proteinase K) or protein denaturant. The embedded sample, if it contains an expanding stimulus-responsive monomer, may be expanded with exposure to the appropriate stimulus (e.g., a salt concentration change and/or temperature change). The embedded sample is transferred to the specialized slide (slide B). The transfer of the embedded sample to the specialized slide is carried out by sandwiching the embedded sample between the initial slide (slide A) and the specialized slide (slide B), inverting the embedded sample so that the specialized slide is underneath the embedded sample, and removing the initial slide. The embedded sample is optionally further agitated (e.g., gently shaken) and/or treated with a separation reagent such as a detergent or salt solution prior to or after the embedded sample is sandwiched between the initial slide and the specialized slide. The separation reagent may be introduced via passive diffusion (e.g., immersion) with or without agitation (e.g., sonication) or other physical disruption, or via active flow (e.g., using a pump to force separation reagent into the sandwiched, embedded biological sample)”, and “[O]nce the embedded sample is supported by the specialized slide and the initial slide has been removed, a second hydrogel mixture (hydrogel mixture B) is added to the embedded tissue sample and polymerized such that the tissue sample is embedded in the hydrogel matrix formed from hydrogel mixture B. The embedded biological sample and hydrogel matrices are optionally further immobilized to the specialized slide during the polymerization process or after polymerization with the addition of fixation reagents” (see paragraphs [0396] to [0398] of US 2023/0013775 A1, which is US publication of this instant case), the specification clearly indicates that a first three-dimensional polymerized matrix embedding a biological sample is formed by adding monomers of a first hydrogel to a substrate having an immobilized sample and polymerizing the monomers of the first hydrogel to polymers and a second three-dimensional polymerized matrix is formed by adding monomers of a second hydrogel to a substrate having the first three-dimensional polymerized matrix embedding the biological sample and polymerizing the monomers of the second hydrogel to polymers. Although the specification describes that three-dimensional
polymerized matrices can be hydrogels (see paragraphs [0007] and [0033] of US 2023/0013775 A1, which is US application of this instant application), as shown in above new matter rejection, the specification does not describe phrases “a first polymerizable matrix-forming material” and “a second polymerizable matrix-forming material” and there is no definition for “polymerizable matrix-forming material” in the specification and art. The closest definition in the art related to “polymerizable matrix-forming material” is “polymer matrix” which is the continuous phase of composite materials, in which polymer chains serve as the backbone or host for reinforcing materials such as fibers or particles wherein polymers are macromolecules composed of many repeating units (monomers), which can be natural (e.g., cellulose in wood) or synthetic (e.g., polyethylene in plastic bags) and include thermosetting polymers, thermoplastic polymers and elastomers, and matrix, in this context, refers to the medium in which the reinforcement is embedded (see “Understanding the Polymer Matrix: A Comprehensive Guide”) and the specification describes that a polymer matrix can be hydrogel matrix (see paragraph [0008] of US 2023/0013775 A1, which is US application of this instant application). Since it is known that hydrogels are crosslinked polymer chains with three-dimensional (3D) network structures, which can absorb relatively large amounts of fluid, and are formed by polymerizing hydrogel monomers (see abstract and Figure 3 of Ho et al., Molecules, 27, 2902, 2022), a first three-dimensional polymerized matrix embedding a biological sample can be formed using a first hydrogel monomer and a second three-dimensional polymerized matrix embedding the biological sample can be formed using a second hydrogel monomer. Since the specification does not teach delivering any kind of first polymerizable matrix-forming material such as a thermoplastic polymer or an elastomer to the biological sample immobilized on a first substrate and delivering any kind of second polymerizable matrix-forming material such as an elastomer or a thermoplastic polymer to the first three-dimensional polymerized matrix embedding the biological sample immobilized on a second substrate, it is unpredictable how a first three-dimensional polymerized matrix embedding a biological sample can be formed using any kind of first polymerizable matrix-forming material such as a thermoplastic polymer or an elastomer and a second three-dimensional polymerized matrix embedding the biological sample can be formed using any kind of second polymerizable matrix-forming material such as an elastomer or a thermoplastic polymer as recited in claims 1-3, 5, 7, 13-15, 18, 20, 22, 26, 28, 37, and 45.
Case law has established that “(t)o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’.” In re Wright 990 F.2d 1557, 1561. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) it was determined that “[T]he scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to persons of ordinary skill in the art”. The amount of guidance needed to enable the invention is related to the amount of knowledge in the art as well as the predictability in the art. Furthermore, the Court in Genentech Inc. v Novo Nordisk 42 USPQ2d 1001 held that “[I]t is the specification, not the knowledge of one skilled in the art that must supply the novel aspects of the invention in order to constitute adequate enablement”.
In view of above discussions, the skilled artisan will have no way to predict the experimental results. Accordingly, it is concluded that undue experimentation is required to make the invention as it is claimed. These undue experimentation at least includes to test whether a first three-dimensional polymerized matrix embedding a biological sample can be formed using any kind of first polymerizable matrix-forming material and a second three-dimensional polymerized matrix embedding the biological sample can be formed using any kind of second polymerizable matrix-forming material as recited in claims 1-3, 5, 7, 13-15, 18, 20, 22, 26, 28, 37, and 45.
Conclusion
In the instant case, as discussed above, the level of unpredictability in the art is high, the specification provides one with no guidance that leads one to claimed methods. One of skill in the art cannot readily anticipate the effect of a change within the subject matter to which the claimed invention pertains. Thus given the broad claims in an art whose nature is identified as unpredictable, the unpredictability of that art, the large quantity of research required to define these unpredictable variables, the lack of guidance provided in the specification, the absence of any working example related to claimed invention and the no teaching in the prior art balanced only against the high skill level in the art, it is the position of the examiner that it would require undue experimentation for one of skill in the art to perform the method of the claim as broadly written.
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 7 and 13 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.
Claim 7 is rejected as vague and indefinite. Since the first part of the claim require to yield a detached biological sample by detaching the biological sample embedded in the first three-dimensional polymerized matrix from the first substrate, it is unclear why immobilizing the biological sample embedded in the first three-dimensional polymerized matrix to the second substrate step can happen after the detaching step. Please clarify.
Response to Arguments
Applicant’s arguments with respect to claims 1-3, 5, 7, 13-15, 18, 20, 22, 26, 28, 37, and 45 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
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.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Frank Lu, Ph. D., whose telephone number is (571)272-0746. The examiner can normally be reached Monday to Friday, 9 AM to 5 PM.
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/FRANK W LU/
Primary Examiner, Art Unit 1683
February 19, 2026