DETAILED ACTION
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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 26 January 2026 has been entered.
Election/Restrictions
Claim 103 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 25 January 2024.
Drawings
The drawings were received on 25 January 2024. These drawings are acceptable.
Claim Interpretation
Attention is directed to MPEP 904.01 [R-08.2012].
The breadth of the claims in the application should always be carefully noted; that is, the examiner should be fully aware of what the claims do not call for, as well as what they do require. During patent examination, the claims are given the broadest reasonable interpretation consistent with the specification. See In re Morris, 127 F.3d 1048, 44 USPQ2d 1023 (Fed. Cir. 1997). See MPEP § 2111 - § 2116.01 for case law pertinent to claim analysis.
It is noted with particularity that narrowing limitations found in the specification cannot be inferred in the claims where the elements not set forth in the claims are linchpin of patentability. In re Philips Industries v. State Stove & Mfg. Co, Inc., 186 USPQ 458 (CA6 1975). While the claims are to be interpreted in light of the specification, it does not follow that limitations from the specification may be read into the claims. On the contrary, claims must be interpreted as broadly as their terms reasonably allow. See Ex parte Oetiker, 23 USPQ2d 1641 (BPAI, 1992). In added support of this position, attention is directed to MPEP 2111 [R-11.2013], where, citing In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550-51 (CCPA 1969), is stated:
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.
Additionally, attention is directed to MPEP 2111.01 [R-01.2024], wherein is stated:
II. IT IS IMPROPER TO IMPORT CLAIM LIMITATIONS FROM THE SPECIFICATION
“Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment.” Superguide Corp. v. DirecTV Enterprises, Inc., 358 F.3d 870, 875, 69 USPQ2d 1865, 1868 (Fed. Cir. 2004).
Attention is also directed to MPEP 2111.02 II [R-07.2022]. As stated herein:
II. PREAMBLE STATEMENTS RECITING PURPOSE OR INTENDED USE
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The claim preamble must be read in the context of the entire claim. The determination of whether preamble recitations are structural limitations or mere statements of purpose or use "can be resolved only on review of the entirety of the [record] to gain an understanding of what the inventors actually invented and intended to encompass by the claim" as drafted without importing "'extraneous' limitations from the specification." Corning Glass Works, 868 F.2d at 1257, 9 USPQ2d at 1966. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020) (The court found that the preamble in one patent’s claim is limiting but is not in a related patent); Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation")… (Emphasis added)
Attention is directed to MPEP 2111 [R-10.2019]. As stated therein:
During patent examination, the pending claims must be "given their broadest reasonable interpretation consistent with the specification." The Federal Circuit’s en banc decision in Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) expressly recognized that the USPTO employs the "broadest reasonable interpretation" standard:
The Patent and Trademark Office ("PTO") determines the scope of claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction "in light of the specification as it would be interpreted by one of ordinary skill in the art." In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364[, 70 USPQ2d 1827, 1830] (Fed. Cir. 2004). Indeed, the rules of the PTO require that application claims must "conform to the invention as set forth in the remainder of the specification and the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description." 37 CFR 1.75(d)(1). (Emphasis added).
Attention is directed to MPEP 2173.04 [R-10.2019]. As stated therein:
Breadth of a claim is not to be equated with indefiniteness. In re Miller, 441 F.2d 689, 169 USPQ 597 (CCPA 1971); In re Gardner, 427 F.2d 786, 788, 166 USPQ 138, 140 (CCPA 1970) ("Breadth is not indefiniteness."). A broad claim is not indefinite merely because it encompasses a wide scope of subject matter provided the scope is clearly defined. But a claim is indefinite when the boundaries of the protected subject matter are not clearly delineated and the scope is unclear. For example, a genus claim that covers multiple species is broad, but is not indefinite because of its breadth, which is otherwise clear. But a genus claim that could be interpreted in such a way that it is not clear which species are covered would be indefinite (e.g., because there is more than one reasonable interpretation of what species are included in the claim). (Emphasis added)
Claim Rejections - 35 USC § 112, Second Paragraph / (b)
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.
Standard for Definiteness.
Attention is directed to MPEP 2171 [R-11.2013]:
Two separate requirements are set forth in 35 U.S.C. 112(b) and pre-AIA 35 U.S.C. 112, second paragraph, namely that:
(A) the claims must set forth the subject matter that the inventor or a joint inventor regards as the invention; and
(B) the claims must particularly point out and distinctly define the metes and bounds of the subject matter to be protected by the patent grant.
The first requirement is a subjective one because it is dependent on what the inventor or a joint inventor for a patent regards as his or her invention. Note that although pre-AIA 35 U.S.C. 112, second paragraph, uses the phrase "which applicant regards as his invention," pre-AIA 37 CFR 1.41(a) provides that a patent is applied for in the name or names of the actual inventor or inventors.
The second requirement is an objective one because it is not dependent on the views of the inventor or any particular individual, but is evaluated in the context of whether the claim is definite — i.e., whether the scope of the claim is clear to a hypothetical person possessing the ordinary level of skill in the pertinent art.
Attention is directed to MPEP 2173.02 I [R-01.2024]:
During prosecution, applicant has an opportunity and a duty to amend ambiguous claims to clearly and precisely define the metes and bounds of the claimed invention. The claim places the public on notice of the scope of the patentee’s right to exclude. See, e.g., Johnson & Johnston Assoc. Inc. v. R.E. Serv. Co., 285 F.3d 1046, 1052, 62 USPQ2d 1225, 1228 (Fed. Cir. 2002) (en banc). As the Federal Circuit stated in Halliburton Energy Servs., Inc. v. M-I LLC, 514 F.3d 1244, 1255, 85 USPQ2d 1654, 1663 (Fed. Cir. 2008):
“We note that the patent drafter is in the best position to resolve the ambiguity in the patent claims, and it is highly desirable that patent examiners demand that applicants do so in appropriate circumstances so that the patent can be amended during prosecution rather than attempting to resolve the ambiguity in litigation.”
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During examination, after applying the broadest reasonable interpretation to the claim, if the metes and bounds of the claimed invention are not clear, the claim is indefinite and should be rejected. Packard, 751 F.3d at 1310 (“[W]hen the USPTO has initially issued a well-grounded rejection that identifies ways in which language in a claim is ambiguous, vague, incoherent, opaque, or otherwise unclear in describing and defining the claimed invention, and thereafter the applicant fails to provide a satisfactory response, the USPTO can properly reject the claim as failing to meet the statutory requirements of § 112(b).”); Zletz, 893 F.2d at 322, 13 USPQ2d at 1322.
Attention is also directed to MPEP 2173.02 III B [R-01-2024], which states in part:
To comply with 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, applicants are required to make the terms that are used to define the invention clear and precise, so that the metes and bounds of the subject matter that will be protected by the patent grant can be ascertained. See MPEP § 2173.05(a), subsection I. It is important that a person of ordinary skill in the art be able to interpret the metes and bounds of the claims so as to understand how to avoid infringement of the patent that ultimately issues from the application being examined. See MPEP § 2173.02, subsection II (citing Morton Int ’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1470 (Fed. Cir. 1993)); see also Halliburton Energy Servs., 514 F.3d at 1249, 85 USPQ2d at 1658 (“Otherwise, competitors cannot avoid infringement, defeating the public notice function of patent claims.”). Examiners should bear in mind that “[a]n essential purpose of patent examination is to fashion claims that are precise, clear, correct, and unambiguous. Only in this way can uncertainties of claim scope be removed, as much as possible, during the administrative process.” Zletz, 893 F.2d at 322, 13 USPQ2d at 1322 [Fed. Cir. 1989]. (Emphasis added)
Attention is also directed to MPEP 2173.04 [R-10-2019], which states in part:
A broad claim is not indefinite merely because it encompasses a wide scope of subject matter provided the scope is clearly defined. But a claim is indefinite when the boundaries of the protected subject matter are not clearly delineated and the scope is unclear. For example, a genus claim that covers multiple species is broad, but is not indefinite because of its breadth, which is otherwise clear. But a genus claim that could be interpreted in such a way that it is not clear which species are covered would be indefinite (e.g., because there is more than one reasonable interpretation of what species are included in the claim).
Holding and Rationale
Claim 86 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.
The terms “useful”, “facilitating” and “significantly” in claim 86 are relative terms which render the claim indefinite. The terms “useful”, “facilitating” and “significantly” are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
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.
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.
Admissions as Prior Art.
Attention is directed to MPEP 2129 Admissions as Prior Art [R-07.2022], which states in part:
I. ADMISSIONS BY APPLICANT CONSTITUTE PRIOR ART
A statement by an applicant in the specification or made during prosecution identifying the work of another as "prior art" is an admission which can be relied upon for both anticipation and obviousness determinations, regardless of whether the admitted prior art would otherwise qualify as prior art under the statutory categories of 35 U.S.C. 102. Riverwood Int’l Corp. v. R.A. Jones & Co., 324 F.3d 1346, 1354, 66 USPQ2d 1331, 1337 (Fed. Cir. 2003); Constant v. Advanced Micro-Devices Inc., 848 F.2d 1560, 1570, 7 USPQ2d 1057, 1063 (Fed. Cir. 1988). Where the admitted prior art anticipates the claim but does not qualify as prior art under any of the paragraphs of 35 U.S.C. 102, the claim may be rejected as being anticipated by the admitted prior art without citing to 35 U.S.C. 102.
Attention is also directed to Ex parte Shirley, (BPAI, 2009) Appeal No. 2009002352, which, at pages 21 and 26, states:
The Specification’s omission of the term “prior art” and inclusion of the prior-art disclaimer may initially appear to indicate that Appellants do not consider the single-step soft bake process to constitute prior art. To place these latter, contraindicative factors into the proper context though, we note that patent-application drafters regularly endeavor to avoid the indiscriminate or imprudent use of the descriptive label, “prior art.” See Riverwood Intern. Corp. v. R.A. Jones & Co., Inc., 324 F.3d 1346, 1354 (Fed. Cir. 2003) (citing In re Fout, 675 F.2d 297, 300 (CCPA 1982)) for the proposition that “section 102 is not the only source of … prior art. Valid prior art may be created by the admissions of the parties”); In re Nomiya, 509 F.2d 566, 571 (CCPA 1975) (holding that an Applicant’s labeling of certain figures as “prior art,” ipsissimis verbis, constituted an admission that the pictured subject matter was prior art relative to Applicant’s invention); MPEP § 21294 (instructing that “the examiner must determine whether the subject matter identified as ‘prior art’ is applicant’s own work, or the work of another. In the absence of another credible explanation, examiners should treat such subject matter as the work of another”).
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The Specification’s omission of the term “prior art” and inclusion of the boilerplate prior-art disclaimer do not change our conclusion. In view of the record as a whole, these factors are ineffective in shielding Appellants from having their prior-art admissions treated as such.
Standard for Obviousness.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
Attention is directed to In re Jung, 98 USPQ2d 1174, 1178 (Fed. Cir. 2011) wherein is stated:
There has never been a requirement for an examiner to make an on-the-record claim construction of every term in every rejected claim and to explain every possible difference between the prior art and the claimed invention in order to make out a prima facie rejection. This court declines to create such a burdensome and unnecessary requirement. “[Section 132] does not mandate that in order to establish prima facie anticipation, the PTO must explicitly preempt every possible response to a section 102 rejection. Section 132 merely ensures that an applicant at least be informed of the broad statutory basis for the rejection of his claims, so that he may determine what the issues are on which he can or should produce evidence.” Chester, 906 F.2d at 1578 (internal citation omitted). As discussed above, all that is required of the office to meet its prima facie burden of production is to set forth the statutory basis of the rejection and the reference or references relied upon in a sufficiently articulate and informative manner as to meet the notice requirement of § 132. As the statute itself instructs, the examiner must “notify the applicant,” “stating the reasons for such rejection,” “together with such information and references as may be useful in judging the propriety of continuing prosecution of his application.” 35 U.S.C. § 132.
Attention is directed to the decision in KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007):
When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill in the art has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
It is further noted that prior art is not limited to the four corners of the documentary prior art being applied. Prior art includes both the specialized understanding of one of ordinary skill in the art, and the common understanding of the layman. It includes “background knowledge possessed by a person having ordinary skill in the art. . . [A] court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1396.
Suggestion, teaching or motivation does not have to be explicit and “may be found in any number of sources, including common knowledge, the prior art as a whole or the nature of the problem itself’” Pfizer, Inc. v. Apotex, Inc. 480 F.3d 1348, 82 USPQ2d 1321 (Fed. Cir. 2007) citing Dystar Textilfarben GMBH v. C. H. Patrick Co., 464 F.3d 1356 (Fed. Cir. 2006).
Holding and Rationale
Claim(s) 65-67, 69-70, 73, 76-77, 79-83, 85, 87-90, 93, 96, 99, 101, 104-106, and 108 are rejected under 35 U.S.C. 103 as being unpatentable over US 2014/0335511 A1 (Glaser et al.) in view of US 2011/0259744 A1 (Moyle), US 2021/0247316 A1 (Bava), US 2010/0136114 A1 (Mao), US 2005/0288796 A1 (Awad et al.), US 2019/0358312 A1 (Irvine et al.), CA 2909344 A1 ( Rogers et al.), US 2021/0253987 A1 (Engler et al.), US 2020/0353120 A1 (Zhan et al.), US 2003/0087985 A1 (Hubbell et al.), and US 2002/0164656 A1 (Hoeffer et al.), applicant’s admissions and US 2008/0032328 A1 (Cline et al.).
Glaser et al., at paragraphs [0005], [0032] and [0033], teach:
[0005] Moreover, the various sub-steps of washing, fixing, dehydrating, hydrating, clearing, embedding, mounting, cryoprotecting, freezing, thawing, and/or staining tissue specimens/sections, removing embedding medium from tissue specimens/sections, and/or processing tissue specimens/sections with histochemistry, IHC, IF, ISH and/or FISH can last between a few seconds and several months and are, thus, very time-consuming as well as tedious and cumbersome. (Emphasis added)
[0032] The term "processing biological tissue for microscopic examination" collectively refers to methods known in the art such as: washing a biological tissue sample (henceforth referred to as "tissue specimen") with a medium, such as tap water, distilled water, and/or buffer; fixing a tissue specimen with a fixative, such as formaldehyde, acetone, and/or other chemicals; dehydrating a tissue specimen with a medium, such as alcohol; hydrating a tissue specimen with a medium, such as water; clearing a tissue specimen with a clearing medium, such as xylene; embedding a tissue specimen into an embedding medium, such as paraffin, methacrylate, or polyethylene glycol; mounting a tissue specimen with a mounting medium, such as celloidin; cryoprotecting a tissue specimen with a medium, such as sucrose solution; freezing a tissue specimen with a freezant, such as liquid nitrogen or isopentane cooled down with dry ice; sectioning a tissue specimen with a cutting device, such as a tissue slicer, tissue chopper, microtome, ultramicrotome, vibratome, sliding microtome, tetrander sliding microtome, cryostat, or cryomicrotome; thawing a tissue section; washing a tissue section with a medium, such as tap water, distilled water, and/or buffer; fixing a tissue section with a fixative, such as formaldehyde, acetone, and/or other chemicals; removing embedding medium from a tissue section with a medium, such as alcohol; removing mounting medium from a tissue section with a medium, such as water; dehydrating a tissue section with a medium such as alcohol; hydrating a tissue section with a medium, such as water; mounting a tissue section on a slide suitable for microscopic examination, such as a glass slide; embedding a tissue section into an embedding medium, such as one or more synthetic resins or glycerine; staining a tissue specimen/section with one or more dyes, such as hematoxylin and/or eosin in order to give contrast to the tissue and to highlight particular features of interest; processing a tissue specimen/section with histochemistry, which refers to staining a tissue specimen/section with the underlying mechanistic chemistry understood; processing a tissue specimen/section with immunohistochemistry (IHC) and/or fluorescence immunohistochemistry/immunofluorescence (IF) in order to detect one or more antigens, such as proteins within the tissue specimen/section, by exploiting the principles of antibodies and/or antibody mimetics binding specifically to antigens in biological tissues, including the specific processes known in the art for IHC and IF for sample preparation; sample labeling with primary, secondary and/or tertiary monoclonal and/or polyclonal antibodies, and/or with antibody mimetics, such as affibody molecules, affilins, affitins, anticalins, avimers, DARPins, fynomers, Kunitz domain peptides, and/or monobodies, and/or sample counterstaining, and/or processing a tissue specimen/section with in situ hybridization (ISH) and/or fluorescence in situ hybridization (FISH) in order to localize a specific DNA or RNA sequence within the tissue specimen/section by exploiting the principles of hybridization of labeled complementary DNA or RNA strands to the specific DNA or RNA sequences, including the specific processes known in the art for ISH and FISH for sample preparation, sample labeling, and/or sample counterstaining, as well as any conceivable combination of one or more of these methods. As those skilled in the art will appreciate, the present description of the term "processing biological tissue for microscopic examination" is intended in an illustrative rather than in a limiting sense. (Emphasis added)
[0033] The term "microscopy" collectively refers to all kinds of microscopy known in the art such as: bright field microscopy; dark field microscopy; fluorescence microscopy; confocal laser scanning microscopy; spinning disc confocal microscopy; digital microscopy; fluorescence interference contrast microscopy; phase contrast microscopy; x-ray microscopy; the generation of two-dimensional and three-dimensional virtual slides with slide scanners and special microscope setups; stereo microscopy; transmission electron microscopy; stimulated emission depletion microscopy; photoactivated localization microscopy; stochastic optical reconstruction microscopy; fluorescence resonance energy transfer microscopy; and to all kinds of scanning probe microscopy, such as atomic force microscopy, ballistic electron emission microscopy, electrostatic force microscopy, electrochemical scanning tunneling microscopy, force modulation microscopy, kelvin probe force microscopy, magnetic force microscopy, magnetic resonance force microscopy, scanning near-field scanning optical microscopy, piezo force microscopy, photon scanning tunneling microscopy, photothermal microspectroscopy/microscopy, scanning atom probe microscopy, scanning capacitance microscopy, scanning electrochemical microscopy, scanning electron microscopy, scanning gate microscopy, scanning ion-conductance microscopy, spin polarized scanning tunneling microscopy, scanning thermal microscopy, scanning tunneling microscopy, scanning voltage microscopy, scanning Hall probe microscopy, and scanning SQUID microscopy. As those skilled in the art will appreciate, the present description of the term "microscopy" is intended in an illustrative rather than in a limiting sense. (Emphasis added)
Glaser et al., at paragraph [0031] teach the types of tissue that can be used. As disclosed therein:
[0031] The term "biological tissue" refers to: single cells from humans and animals, such as red blood cells or one or more human or animal cells grown ex vivo in a cell culture; single cells from plants, such as one or more plant cells grown ex vivo in a cell culture; organ parts from humans and animals consisting of more than one cell and, thus, of one or more types of cells, such as a tissue sample or tissue section, collected during a biopsy, during surgery, or post mortem, or grown in a tissue culture; plant parts consisting of more than one cell, such as a leaf from a tree, and sections thereof; entire organs from humans and animals, such as a heart, kidney, brain, or liver, collected during an excisional biopsy, during surgery, or post mortem, and sections thereof; organ systems from humans and animals, such as the gastrointestinal system or the genitals, collected during an excisional biopsy, during surgery, or post mortem, and sections thereof; body parts from humans and animals such as a head, arm, hand, leg or foot, or parts of such body parts, collected during surgery or post mortem, or separated from a human or animal body by an accident, and sections thereof; plant parts such as a branch or root from a tree, and sections thereof; entire human and animal bodies, such as a human body destined for post mortem autopsy in a pathology or forensic medicine lab, or an animal body destined for examination as part of a scientific experiment, and sections thereof; and entire plants such as a flower or a tree. As those skilled in the art will appreciate, the present description of the term "biological tissue" is intended in an illustrative rather than in a limiting sense. (Emphasis added)
Glaser et al., at paragraph [0046], teach:
To provide a sense of scale, particular examples of system 500 can be sized and configured for handing one or more tissue specimens with volumes between, for example, about 1.0 .mu.m.sup.3 to about 1.0 m.sup.3; tissue sections with area typically between 1.0 .mu.m.sup.2 and 1.0 m.sup.2; and tissue specimens and tissue sections having a thickness typically between 0.000001 mm and 1,000 mm. (Emphasis added)
The above showing is deemed to fairly suggest limitations of claims 65, 69-70, 73, 76, 77, 79, 104-106, and 108. As seen above, Glaser et a., in paragraph [0032], teach “embedding a tissue specimen into an embedding medium, such as paraffin, methacrylate, or polyethylene glycol”. Such is deemed to fairly suggest the “sample-carrier construct” of claim 65. The fact that the embedding material can be paraffin or polyethylene glycol is deemed to fairly suggest limitations of claim 76.
The fact that it several months may lapse prior to testing speaks to the sample being stored for anywhere from less than a day to several months. Such is deemed to fairly suggest limitation of claim 90.
While Glaser et al., teach mounting the fixed tissue sample on a mounting medium, they have not been found to teach using hydrogel.
Moyle, at paragraph [0285], teach placing a tissue section on surface of a hydrogel. As stated therein:
0285] As noted above, a positively charged hydrogel can be employed to prevent a negatively charged sample (e.g., a nucleic acid) from running through the IH. A working sensor can be prepared in which the only component is an IH or other light transmitting material, e.g., a porous glass such as Vycor. However, for many analyses a preferred arrangement consists of one or more gel layers in addition to the IH (FIG. 13). This permits the charged or uncharged IH gel to be thinner than the gel that contains the sample and detection reagent, a phenomenon that increases the sensitivity of the device. The IH of sensors that employ total internal reflection fluorescence (TIRF) to monitor the analyte-detection complex must have a higher refractive index than those of other surfaces that are in contact with it. The use of an additional gel also permits samples such as tissue sections to be applied on the surface of a hydrogel distant from the IH. (Emphasis added)
While Moyle teaches placement of a tissue section on a hydrogel carrier, they have not been found to teach using hydrogel in combination with other compounds, e.g., polyethylene glycol (PEG), or an agar such as agarose.
Bava, at paragraph [0006], teaches:
In some embodiments, the tissue section is obtained from a fresh tissue sample or a frozen tissue sample. In some embodiments, the tissue section is obtained from a tissue sample that has been fixed. In some embodiments, the tissue sample is fixed in one or more of: paraffin, a wax, a resin, an epoxy, an agar, a glycol, a hydrogel, or a combination thereof. In some embodiments, the plurality of tissue sections are serial sections from a tissue sample. In some embodiments, the average thickness of the plurality of tissue sections is about 0.1 to about 100 micrometers. In some embodiments, methods of processing a biological sample provided herein further include fixing the tissue section prior to step (a). In some embodiments, the tissue section is obtained from a tissue sample that has been permeabilized. In some embodiments, methods of processing a biological sample provided herein further include permeabilizing the tissue section prior to step (a). In some embodiments, methods of processing a biological sample provided herein further include fixing the tissue section prior to permeabilizing. In some embodiments, methods of processing a biological sample provided herein further include permeabilizing the tissue section prior to or after step (b). In some embodiments, the tissue section is permeabilized via electroporation. In some embodiments, the tissue section is permeabilized via by contacting the tissue section with a permeabilization agent. (Emphasis added)
The above showing is deemed to fairly suggest limitations of claim 65. As seen above, the tissue section can be one that is fixed in not only paraffin or a wax, but that it may be done as a combination of two or more, which fairly suggests paraffin and a hydrogel. The manner in which one is placed on the other is deemed to be a matter of an obvious design choice. Given such, the above cited teachings are deemed to fairly suggest the “sample-carrier construct” of claim 65, part A).
Bava, at paragraph [0102], teaches the thickness of the tissue section. As stated therein:
For example, the thickness of the tissue section can be at least 0.1, 0.2, 0.3, 0.4, 0.5, 0.7, 1.0, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 14, 15, 20, 30, 40, or 50 micrometers. Thicker sections can also be used if desired or convenient, e.g., at least 70, 80, 90, or 100 micrometers or more. (Emphasis added)
The above showing is deemed to fairly teach limitations of claim 73.
Mao, at paragraph [0015], teach:
[0015] In various aspects, the matrix can comprise a material such as a fibrin, a fibrinogen, a collagen, a polyorthoester, a polyvinyl alcohol, a polyamide, a polycarbonate, ab agarose, an alginate, a poly(ethylene) glycol, a polylactic acid, a polyglycolic acid, a polycaprolactone, a polyvinyl pyrrolidone, a marine adhesive protein, a cyanoacrylate, a polymeric hydrogel, analogs, or a combination thereof. In some preferred configurations, the matrix material can be a polymeric hydrogel.
Mao, at paragraph [0042], teach:
[0042] FIG. 19 is a series of images depicting stained tissue sections of tissue with PEG microchanneled hydrogel with macrochannels encapsulating hMSC-derived adipogenic cells implanted for twelve weeks. (Emphasis added)
The above showing is deemed to fairly suggest limitations of claims 76 and 79.
Awad et al., in paragraph [0042], teach:
In the preferred embodiment, the moldable biologic material is a hydrogel carrier material. Suitable hydrogel materials may include: 1) biological gels such as collagen, hyaluronic acid, fibrin, gelatin, elastin or other biological materials; 2) marine organism-derivatives such as, alginate, agarose, or chitosan gels; or 3) synthetic hydrogels such as Pluronic/F-12 and PEO/PEG gels. (Emphasis added)
The above showing is deemed to fairly suggest limitations of claims 79 and 80. While Awad et al. teach using agarose, they do not teach the concentration of same.
Irvine, at paragraph [0292], teach histology sections were prepared and embedded in “3 wt % low melting point agarose”.
The above showing is deemed to fairly suggest limitations of dependent claim 81.
Rogers et al., at paragraph [0211], teach methods of producing histological sections of tissue.
Rogers et al., at paragraph [0274], teach:
Polymers useable in the methods, devices and components include, but are not limited to, plastics, elastomers, thermoplastic elastomers, elastoplastics, thermoplastics and acrylates. (Emphasis added)
In view of the above showing, it would have been obvious to one of ordinary skill in the art at the time of the invention to have incorporated the use of thermoplastic elastomers disclosed by Rogers et al., in the method of Glaser et al., Awad et al., and Irvine et al., and would have been motivated to have done so given the properties of such thermoplastic elastomers.
The above showing is deemed to fairly suggest limitations of claims 82 and 83.
Neither Glaser et al., Moyle, Bava, Mao Awad, Irvine, nor Rogers et al., have been found to disclose a hydrogel carrier that “comprises a Young’s modulus of 5 kPa to 30 kPa” (claim 85).
Engler et al., at paragraph [0404], teach:
Using the parallel plate flow chamber (PPFC) (Beni et al., 2020), cells are isolated based on adhesion strength and seeded onto photopatterned hydrogels with alternating soft and stiff elasticity profiles that match Young's moduli of softer stromal and stiffer tumor ECM for each type of cancer (FIGS. 23A-23B), i.e. 0.3 and 1.5 kPa for mammary (Cox and Erler, 2011; Paszek et al., 2005), 4 and 20 kPa for lung (Burgstaller et al., 2017; Pankova et al., 2019; White, 2015), and 10 and 30 kPa for prostate (Ahn et al., 2010; L. Krupski et al., 2010; Zhai et al., 2010). (Emphasis added)
As evidenced above, it was well known in the art at the time of the invention to employ hydrogels with different Young’s modulus, depending on the type of tissue. As evidenced above, the full range of Yong’s modulus recited in claim 85 was known in the art. Given such, it would have been obvious to the ordinary artisan to employ hydrogels with the same properties for the same function.
Neither Glaser et al., Moyle, Bava, Mao Awad, Irvine, Rogers et al., nor Engler et al., have been found to disclose the adsorption of water/fluids that are between the carrier substrate and the tissue section.
Zhao et al.., at paragraph [0018], teach:
[0018] FIGS. 2A-B schematically illustrate a dry double sided material in the form of a tape according to an embodiment of the present invention, with FIG. 2A depicting placement of the dry double sided tape (hereinafter sometimes referred to as “DST”) between two wet tissues according to an embodiment of the present invention (left) and attachment of a hydrogel and/or various other materials to a wet tissue surface using the DST according to an embodiment of the present invention (right), and FIG. 2B depicting a dry-crosslinking mechanism for the DST according to an embodiment of the present invention which integrates drying of interfacial liquid (e.g., water) by swelling of the DST, instant temporary crosslinking, and fast covalent crosslinking. (Emphasis added)
As evidenced above, the tissue surface is “wet”, which speaks to water being between the surface of the tissue and the hydrogel. Such a showing is deemed to fairly suggest a limitation of claim 86.
Neither Glaser et al., Moyle, Bava, Mao Awad, Irvine, Rogers et al., Engler et al., nor Zhao et al., have been found to disclose the water content of hydrogel carriers.
Hubbell et al., at page 23, right column, in Table 17, teach the water content of a variety of hydrogels. As disclosed therein:
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328
588
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Greyscale
The above showing is deemed to fairly teach limitations of claim 87.
In view of the above showing that hydrogels comprise from 82.3 % to 94.5% water, such would have been an inherent property to the hydrogels of Glaser et al., Awad et al., Irvine et al., Rogers et al., Engler et al., and Zhao et al.
Neither Glaser et al., Moyle, Bava, Mao Awad, Irvine, Rogers et al., Engler et al., Zhao et al., nor Hubbell et al., have been found to disclose the composition of the “receiving substrate”.
Hoeffer et al., at paragraph [0095], teach:
[0095] Glass slides (Fisher Catalog No. 12-544-4) are soaked in an acid bath (1 hour in 0.1 M HCl), then washed with water and dried at room temperature. The slides should not be aggressively dried, such as in an oven. The slides are next soaked in a silane solution overnight at room temperature (5% APTES (3-aminopropyl-triethoxysilane, Aldrich 28,177-8), 0.3% DIEA (Sigma) v/v in EtOH). The slides may be sonicated for 10-15 minutes right after being placed in the APTES solution. (Emphasis added)
In view of the above showing, it would have been obvious to one of ordinary skill in the art at the time of the invention to have modified the method of Glaser et al., whereby the tissue section is not just mounted on a glass slide, but is mounted on a glass slide that has been treated with APTES as disclosed by Hoeffer et al.
The above showing is deemed to fairly suggest a limitation of claims 88 and 89.
Applicant, at page 33, admits:
[0074] As used herein, the term "hydrogel" or "hydrogel carrier" refers to a three dimensional polymeric structure that is substantially insoluble in water, but which is capable of absorbing and retaining water (e.g. large quantities of water) to form a substantially stable, often soft and pliable, structure. In embodiments, water can penetrate in between polymer chains of a polymer network, subsequently causing swelling and the formation of a hydrogel. In embodiments, hydrogels are super-absorbent (e.g., containing more than about 90% water) and can be comprised of natural or synthetic polymers. Hydrogels can contain over 99% water and may include natural or synthetic polymers, or a combination thereof. Hydrogels also possess a degree of flexibility very similar to natural tissue, due to their significant water content. A detailed description of suitable hydrogels may be found in published U.S. patent application 20100055733, herein specifically incorporated by reference. By "hydrogel subunits" or "hydrogel precursors" is meant hydrophilic monomers, prepolymers, or polymers that can be crosslinked, or "polymerized", to form a three-dimensional (3D) hydrogel network.
Applicant, at page 119, paragraph [0276], admits:
[0276] In embodiments, the methods are performed in situ in tissue sections that have been prepared according to methodologies known in the art. Methods for permeabilization and fixation of cells and tissue samples are known in the art, as exemplified by Cremer et al., The Nucleus: Volume 1: Nuclei and Subnuclear Components, R Hancock (ed.) 2008; and Larsson et al., Nat. Methods (2010) 7:395-397, the content of each of which is incorporated herein by reference in its entirety. In embodiments, the tissue section is cleared (e.g., digested) of proteins, lipids, or proteins and lipids. (Emphasis added)
The aspect that the tissue sections had been prepared “according to methodologies known in the art” is deemed to render obvious the time and temperatures at which the sample is stored (limitations of claims 90 and 93). It is further noted that the storage temperature of “less than 25 °C” is deemed to encompass normal room temperature.
Applicant, at page 124, paragraph [0285], admits:
[0285] In embodiments, the method further includes subjecting the tissue section to
expansion microscopy methods and techniques (e.g., prior to detection). Expansion allows individual targets (e.g., mRNA or RNA transcripts) which are densely packed within a cell, to be resolved spatially in a high-throughput manner. Expansion microscopy techniques are known in the art and can be performed as described in US 2016/0116384 and Chen et al., 20 Science, 347, 543 (2015), each of which are incorporated herein by reference in their entirety. (Emphasis added)
Applicant, at page 146, paragraph [0335], admits:
[0335] H&E staining: Tissue sections were then fixed with 4% PFA in PBS for 30 min.
Samples were then H&E stained using methods known in the art and imaged using a color camera. (Emphasis added)
While applicant has admitted that methods of using H&E staining of tissue section was known in the art, it is not clear if applicant has admitted the use of a camera so to obtain images was also known in the art.
Cline et al., at paragraph [0049], teaches:
[0049] Next, the tissue section is labeled with a morphological marker such as the traditional H&E dyes, and placed at the same location under the microscope. The location of the specimen under the microscope is controlled with electronic, magnetic, optical or mechanical sensors so that the specimen can be repeatedly located close to the same position for the next image acquisition. The microscope is designed such that it can acquire both bright field and fluorescent images. One such microscope may involve calibrated multiple optical paths and multiple cameras. After which, a bright field image of the tissue section is obtained using a digital camera. (Emphasis added)
In view of the above showings, it was well established in the art that one would know how to obtain tissue samples, cut the tissue into sections, treat the tissue sample with a stain, embedding the sample, use of hydrogel that can comprise a variety of components, use imaging reagents, obtain images via a camera, etc. as such steps and reactions were well known and developed. In view of the ability to obtain images of a variety of tissue samples, one would have been amply motivated to produce such as it would enable the storage of tissue information as well as enable the sharing of such information. In view of the well-developed state of the art, said ordinary artisan would have had a most reasonable expectation of success.
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 65-67, 69-70, 73, 76-77, 79-83, 85, 87-90, 93, 96, 99, 101, 104-106, and 108 are rejected under 35 U.S.C. 103 as being unpatentable over US 2014/0335511 A1 (Glaser et al.) in view of US 2011/0259744 A1 (Moyle), US 2021/0247316 A1 (Bava), US 2010/0136114 A1 (Mao), US 2005/0288796 A1 (Awad et al.), US 2019/0358312 A1 (Irvine et al.), CA 2909344 A1 ( Rogers et al.), US 2021/0253987 A1 (Engler et al.), US 2020/0353120 A1 (Zhan et al.), US 2003/0087985 A1 (Hubbell et al.), and US 2002/0164656 A1 (Hoeffer et al.), applicant’s admissions and US 2008/0032328 A1 (Cline et al.).
Response to arguments
Applicant’s representative, at pages 6-10 of the response of 26 January 2026, hereinafter the response, traverses the rejection of claims under 35 USC 103(a).
At page 8 of the response argument is presented that the Office action does not take into account the requirement of there being “a sample-carrier construct comprising the hydrogel carrier and the tissue section”. This argument has been considered and has not been found persuasive. As noted above, Bava, at paragraph [0006], teaches:
In some embodiments, the tissue section is obtained from a fresh tissue sample or a frozen tissue sample. In some embodiments, the tissue section is obtained from a tissue sample that has been fixed. In some embodiments, the tissue sample is fixed in one or more of: paraffin, a wax, a resin, an epoxy, an agar, a glycol, a hydrogel, or a combination thereof. In some embodiments, the plurality of tissue sections are serial sections from a tissue sample. In some embodiments, the average thickness of the plurality of tissue sections is about 0.1 to about 100 micrometers. In some embodiments, methods of processing a biological sample provided herein further include fixing the tissue section prior to step (a). In some embodiments, the tissue section is obtained from a tissue sample that has been permeabilized. In some embodiments, methods of processing a biological sample provided herein further include permeabilizing the tissue section prior to step (a). In some embodiments, methods of processing a biological sample provided herein further include fixing the tissue section prior to permeabilizing. In some embodiments, methods of processing a biological sample provided herein further include permeabilizing the tissue section prior to or after step (b). In some embodiments, the tissue section is permeabilized via electroporation. In some embodiments, the tissue section is permeabilized via by contacting the tissue section with a permeabilization agent. (Emphasis added)
The above showing is deemed to fairly suggest limitations of claim 65. As seen above, the tissue section can be one that is fixed in not only paraffin or a wax, but that it may be done as a combination of two or more, which fairly suggests paraffin and a hydrogel. The manner in which one is placed on the other is deemed to be a matter of an obvious design choice. Given such, the above cited teachings are deemed to fairly suggest the “sample-carrier construct” of claim 65, part A).
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 65-67, 69-70, 73, 76-77, 79-83, 85, 87-90, 93, 96, 99, 101, 104-106, and 108 are rejected under 35 U.S.C. 103 as being unpatentable over US 2014/0335511 A1 (Glaser et al.) in view of US 2011/0259744 A1 (Moyle), US 2021/0247316 A1 (Bava), US 2010/0136114 A1 (Mao), US 2005/0288796 A1 (Awad et al.), US 2019/0358312 A1 (Irvine et al.), CA 2909344 A1 ( Rogers et al.), US 2021/0253987 A1 (Engler et al.), US 2020/0353120 A1 (Zhan et al.), US 2003/0087985 A1 (Hubbell et al.), and US 2002/0164656 A1 (Hoeffer et al.), applicant’s admissions and US 2008/0032328 A1 (Cline et al.).
Conclusion
Objections and/or rejections which appeared in the prior Office action and which have not been repeated hereinabove have been withdrawn.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US 2001/0023372 A1 (Chen et al.), at paragraph [0051], teach:
Thereafter, both treated, fixed tissue samples were stored for seven days at standard temperature and relative humidity prior to sterility testing. (Emphasis added)
As evidenced above, the aspect of fixing and storing tissue “for seven days at standard temperature” was known in the art.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 Bradley L. Sisson whose telephone number is (571)272-0751. The examiner can normally be reached Monday to Thursday, from 6:30 AM to 5 PM.
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/Bradley L. Sisson/Primary Examiner, Art Unit 1682
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