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 .
Notice of New examiner
The examiner reviewing your application at the PTO has changed. To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to examiner Steven Pohnert .
Claim Status and Formal Matters
This action is in response to papers filed 12/23/2025.
Claims 83-95 are pending.
Claims 83-87, 89-91, 94-95 are amended.
Priority
The instant application was filed 06/02/2022 and is a continuation of 16442395 , filed 06/14/2019 which is a Continuation of PCT/US2017/067996 , filed 12/21/2017, which claims priority from provisional application 62438228 , filed 12/22/2016.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 1/16/2026 is being considered by the examiner.
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 83-95 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 83 is indefinite because it lacks a positive active step relating back to the preamble. The preamble recites an automated method for isolating nucleic acid from one or more tissue samples, wherein the one or more tissue samples are disposed on one or more slides, however the last positive active step is drawn to heating the one or more tissue samples disposed on the one or more slides. Therefore it is unclear as to whether the method is drawn to an automated method for isolating nucleic acid from one or more tissue samples, wherein the one or more tissue samples are disposed on one or more slides or heating the one or more tissue samples disposed on the one or more slides. Further the metes and bounds are unclear what is being automated and/or how automation is done as the independent claim provides no limitations with respect to automation, except the preamble. Further it is unclear how nucleic acids are being isolated as the independent claim provides no steps in which nucleic acids are isolated.
Response to Arguments
This is a new ground of rejection.
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.
Claim(s) 83-90, 92 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bagasra (Nature Protocols (2007) volume 2, pages 2782-2795) and Schagat (Successfully Overcoming the Challenges of Working with FFPE Samples (Nov 2014).
As noted in the MPEP 2111.02, “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.” Further, a preamble is generally not accorded any patentable weight where it merely recites the purpose of a process or the intended use of a structure, and where the body of the claim does not depend on the preamble for completeness but, instead, the process steps or structural limitations are able to stand alone. See In re Hirao, 535 F.2d 67, 190 USPQ 15 (CCPA 1976) and Kropa v. Robie, 187 F.2d 150, 152, 88 USPQ 478, 481 (CCPA 1951). Accordingly, the claim language of "An automated method for isolating nucleic acid from one or more tissue samples, wherein the one or more tissue samples are disposed on one or more slides” merely sets forth the intended use or purpose of the claimed methods, but does not limit the scope of the claims. Specifically the claim does not provide any active steps requiring automation.
MPEP 2106 states: Claim scope is not limited by claim language that
suggests or makes optional but does not require steps to be performed, or
by claim language that does not limit a claim to a particular structure.
However, examples of claim language, although not exhaustive, that may
raise a question as to the limiting effect of the language in a claim are:
(A) “ adapted to ” or “adapted for ” clauses;
(B) “ wherein ” clauses; and
(C) “ whereby ” clauses.
The determination of whether each of these clauses is a limitation in a claim
depends on the specific facts of the case. In Hoffer v. Microsoft Corp., 405
F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that
when a “whereby’ clause states a condition that is material to patentability,
it cannot be ignored in order to change the substance of the invention.” Id.
However, the court noted (quoting Minton v. Nat ’l Ass ’n of Securities
Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003))that a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id.<
The recitation of “thereby generating an eluate, and wherein the eluate comprises one or more isolated nucleic acid molecules from the one or more samples” merely provides for the intended outcome, but does not explicitly limit the active steps of the claims.
Further the specification 0012 teaches, “. treating the sample or samples with an antigen retrieval solution, a buffer, etc.)” Thus the broadest reasonable interpretation of antigen retrieval buffer is any buffer.
With regards to claim 83, Bagasra teaches, “ (C)Preparation of paraffin-fixed tissue slides for in situ PCR analysis TIMING 2h (i) To remove the paraffin from the tissue, firstly incubate the slides in an oven at 80 C for 1h to melt the paraffin. (ii)Dip the slides in xylene (EM grade, benzene-free) solution for 5min, then in100% ethanol (EM grade) for 5min, 90% ethanol (EMgrade) for 5min, 80% ethanol (EM grade) for 5min, 70%(EM grade) ethanol for 5min, 50%(EMgrade) Ethanol for 5 min and then in H2O for 5min.” (page 2788)
Bagasra teaches the treatment of the slides with hydrogen peroxide in PBS (a buffer) step 8, page 2789).
Bagasra teaches treatment with proteinase K in PBS (a proteinase K buffer) step 15, page 2789.
Bagasra teaches heating after proteinase K treatment.
While Bagasra teaches applying a deparaffinization reagent, applying a buffer applying a protease buffer and heating, Bagasra does not specifically teach the release of nucleic acids from the slides.
However, Schagat teaches proteinase K lyses and de-crosslinks nucleic acids (slide 12).
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims the method of Bagasra releases nucleic acids from the tissues. The artisan would be motivated as Schagat teaches heating and proteinase K allow for lysing of the cell and decrosslinking. Thea artisan would have a reasonable expectation of success as the artisan is merely using known methods.
With regards to claim 84-85, Schagat teaches purifying nucleic acids after lysing of the cell and decrosslinking. Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to remove or retrieve liquid containing nucleic acids from the slides to further isolate the nucleic acids. The artisan would be motivated as Schagat teaches isolating of nucleic acids after lysing of the cell and decrosslinking. The artisan would have a reasonable expectation of success as the artisan is merely following the guidance of the art.
With regards to claims 86-87, Schagat teaches PCR amplification to analyses two amplicons (nucleic acids)slide 16.
With regards to claim 88, Schagat teaches sequencing the samples (slide 38, 43-44)
With regards to claim 89-90, Schagat teaches DNA or RNA are in samples (slide 6).
With regards to claim 92, Bagasra and Schagat teach FFPE samples (title)
Claim(s) 94-95 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bagasra (Nature Protocols (2007) volume 2, pages 2782-2795) and Schagat (Successfully Overcoming the Challenges of Working with FFPE Samples (Nov 2014) as applied to claims 83-90, 92 above, and further in view of Roberts (.Automating Immunohistochemistry (2014))
While Bagasra and Schagat teach (a) applying a deparaffinization reagent onto the one or more tissue samples disposed on the one or more slides;(b) restoring antigenicity of the one or more tissue samples by applying an antigen retrieval buffer onto the one or more tissue samples disposed on the one or more slides;(c) applying a protease buffer onto the one or more tissue samples disposed on the one or more slides; and(d) heating the one or more tissue samples disposed on the one or more slides,, they do not specifically teach automating.
MPEP 2144.04 III states:
In reVenner, 262 F.2d 91, 95, 120 USPQ 193, 194 (CCPA 1958) (Appellant argued that claims to a permanent mold casting apparatus for molding trunk pistons were allowable over the prior art because the claimed invention combined “old permanent-mold structures together with a timer and solenoid which automatically actuates the known pressure valve system to release the inner core after a predetermined time has elapsed.” The court held that broadly providing an automatic or mechanical means to replace a manual activity which accomplished the same result is not sufficient to distinguish over the prior art.).
Roberts teaches, “There are about a dozen automated IHC staining systems on the market—both benchtop and floor models—from about half-dozen vendors. Although it may not be easy to tell apart the slides that ultimately emerge from them, the instruments themselves certainly differ vis-à-vis their inherent capacity, throughput and hands-on time required; their ability to accept third-party reagents; or their flexibility and ease-of-use, among other attributes.” Roberts teaches, “For the antibody to gain access to the tissue in IHC processing, paraffin must be removed (typically with xylene or a similar organic reagent). In the vast majority of instances an additional heat-induced antigen (epitope) retrieval (HIER) step is also required that “heats slides to a high temperature to break the formalin bonds,” says Myers. These steps can be performed either prior to introducing the slides into the stainer or as a part of the automated process. Instruments capable of the latter are far more expensive. He notes that the typical sale price of a machine with offline retrieval is $85,000 to $90,000, whereas a machine with online retrieval ranges from $125,000 to $150,000, and “the cost of producing the slide is 30[% to] 40% more for the convenience of online retrieval.” Roberts teaches, “At one time, all automated IHC stainers were operated in batch mode. This allowed for less hands-on time and more efficient use of the instrument, including less reagent lost to dead space compared with a sequential or continuous modality and the ability to use a single set of controls for the entire batch, Whitaker notes. “But the tradeoff for doing that is that it’s not as timely—if you are running each case [set of slides from an individual patient, typically stained with different antibodies] on a case-by-case basis as [it is] requested and cut, of course your turnaround time is much improved.”
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to use an automated staining machine with at least one dispenser and a heating element. The artisan would be motivated as Robert suggests automated slide staining machines as Roberts teaches, “automated IHC stainers are endowed with robotics and process control to perform far more complex and intricate tasks than the more common bulk dip-and-dunk hematoxylin and eosin (H&E) stainers.” The artisan would have a reasonable expectation of success as the artisan is merely using known slide staining machines in known methods.
Claim(s) 91 and 93 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bagasra (Nature Protocols (2007) volume 2, pages 2782-2795) and Schagat (Successfully Overcoming the Challenges of Working with FFPE Samples (Nov 2014) as applied to claims 83-90, 92 above, and further in view of Gatalica (WO2015/116868)
While Bagasra and Schagat teach (a) applying a deparaffinization reagent onto the one or more tissue samples disposed on the one or more slides;(b) restoring antigenicity of the one or more tissue samples by applying an antigen retrieval buffer onto the one or more tissue samples disposed on the one or more slides;(c) applying a protease buffer onto the one or more tissue samples disposed on the one or more slides; and(d) heating the one or more tissue samples disposed on the one or more slides,, they do not specifically teach use of guanidine thiocyanate or micro dissected sample.
However, Gatalica teaches, “00475] Formalin- fixed paraffin-embedded (FFPE) are reviewed by a pathologist for quality control before subsequent analysis. Nucleic acids (DNA and RNA) are extracted from FFPE tissues after microdissection of the fixed slides. Nucleic acids are extracted using phenol-chloroform extraction or a kit such as the QIAamp DNA FFPE Tissue kit according to the manufacturer's instructions (QIAGEN Inc., Valencia, CA).”
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to use micro dissected fixed samples as the samples in the method. The artisan would be motivated as Gatalica teaches micro dissected samples can be used after pathologist. Further the artisan would be motivated to use micro dissected samples to limit nucleic acids to portion of sample of interest. The artisan would have a reasonable expectation of success as the art teaches use of micro dissected sample.
Gatalica teaches use of guanidine isothiocyanate for isolation of nucleic acids(00443).
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to provide guanidine isothiocyanate or guanidine thiocyanate after protease digestion. The artisan would be motivated as Gatalica teaches guanidine isothiocyanate or guanidine thiocyanate for isolation of nucleic acids from samples. The artisan would have a reasonable expectation of success as the artisan is merely using known reagents for isolation of nucleic acids by known methods.
Summary
No claims are allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEVEN C POHNERT PhD whose telephone number is (571)272-3803. The examiner can normally be reached Monday- Friday about 6:00 AM-5:00 PM, every second Friday off.
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/Steven Pohnert/ Primary Examiner, Art Unit 1683
