DETAILED ACTION
Applicant’s remarks submitted on 2/3/2026 is acknowledged. No amendment was submitted with the remarks.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 2/27/2026 has been entered.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Maintained Rejection: Claims 18-19, 22, 24-25, 27, and 30-33 are rejected under 35 U.S.C. 103 as being unpatentable over Li (US2013/0065252; Of Record) in view of Tigges (Metabolic Engin., 2006, Vol. 8(3); p.264-272; Of Record), Gray (WO2018/165385; Of Record), Brown (US2008/0187942; Of Record), Kohn (US2014/0120552; Of Record), Brown2 (US2013/0059312; Of Record), Arena Pharmaceuticals (US2008/0009551; Of Record) and Ignowski (Biotechnol. and Bioengin., 2004, Vol.86 (7); p. 827-834; Of Record).
Regarding claim 18, Li discloses a method for detecting thyroid stimulating and/or thyroid blocking autoantibodies in a sample (“The invention additionally provides a method for detecting thyroid hormone blocking immunoglobulin (TBI) and thyroid hormone stimulating immunoglobulin (TSI) in a test sample," Para [0006]). The test sample of Li can be blood or serum (Para [0036] and [0049]). The method of detection of Li comprises: “(a) contacting transgenic cells with a sample suspected of comprising thyroid stimulating and/or thyroid blocking autoantibodies (b) contacting the transgenic cells and the TSH with i) the control sample to produce a first sample, and ii) the test sample to produce a second sample, wherein the contacting is under conditions for binding of the TSH to the chimeric TSHR," Para [0006]). Li embraces an embodiment where the transgenic cells are stably transfected with: (i) a first expression vector comprising a nucleotide sequence that encodes a chimeric thyroid-stimulating hormone (TSH) receptor ("transgenic cells stably transfected with one or more expression vectors comprising…2) a chimeric TSH receptor (TSHR) gene" Para [0048]). The chimeric TSHR is linked to a constitutive promoter. Li discloses the one or more expression vector comprising a synthetic nucleotide sequence that encodes a reporter ("transgenic cells stably transfected with one or more expression vector comprising a 1) a reporter gene (e.g., luciferase gene)" Para [0048]). The synthetic nucleotide sequence is operably linked to a cAMP-inducible promoter inducible ("1) a reporter gene (e.g., luciferase gene) operably linked to a cAMP-inducible promoter," Para [0048]). The one or more expression vectors comprises a chimeric TSHR and a synthetic nucleotide sequence encoding a reporter, and thus, Li embraces embodiments where two expression vectors separately express a chimeric TSHR and a synthetic nucleotide encoding a reporter, as the teaching above implies, and does not require that one expression vector is used to express a chimeric TSHR and synthetic nucleotide sequence encoding a reporter. Li teaches the step of contacting, in a buffer comprising substrate for the modified luciferase reporter (see paragraphs [0049] and [0078]). The luciferase substrate is reconstituted in dithiothreitol, a known buffer, and thus the buffer comprises the substrate for the reporter. Li discloses detecting an intracellular signal associated with expression of the reporter ("and c) measuring the level of expression of the reporter gene (e.g., by detecting bioluminescence resulting from luciferase enzyme activity) in the transgenic cells before the contacting and after the contacting," Para [0066]). Li teaches an increase in in the level of expression of the reporter gene indicates the presence of TSI and a reduction in level of expression of the reporter gene indicates the presence of TBIs, reading on where an increase in intracellular signal indicates the presence of thyroid stimulating autoantibodies and a decrease in intracellular signal indicates the presence of thyroid blocking autoantibodies (see paragraph [0066]). The transgenic cells used by Li are kept at -800C and not allowed to warm until immediately prior to thawing and use in the methods. This is interpreted as thawing the cells and using the thawed cells immediately in the method of detection. With regard to the limitation “wherein the method does not comprise seeding the transgenic cells or contacting the transgenic cells with a lysing agent” as recited in claim 18, Li’s teachings do not require that seeding is performed nor does Li teach or suggest that seeding is a critical aspect of the method of detecting TBI and/or TSI, in as much as it being required to be performed. Additionally, there are no lysing agents present in the method step of contacting taught by Li ("In some embodiments, the TBI assay comprises using CHO-MC4 cells, cell growth medium, bTSH, Thyretain.TM. reaction buffer (Quidel Corp. & Diagnostic Hybrids, Inc., Ohio, USA), luciferase substrate and patient blood serum sample." Para [0049]). Thus, the method taught by Li does not require a step of seeding and does not contact transgenic cells with a lysing agent, as claimed. Furthermore, Li does not teach a step of washing the transgenic cells before contacting the transgenic cells with the sample.
Li does not teach that the synthetic nucleotide encoding the modified luciferase reporter is linked to a constitutive promoter, that the synthetic nucleotide sequence encodes a heterologous cAMP-binding protein fused to the modified reporter, using a luminometer, not diluting the sample, that the nucleotide sequence that encodes the chimeric TSH receptor is at least 85% identical to the nucleotide sequence of SEQ ID NO: 1, that the step of contacting is performed less than about 5 minutes after said thawing, that the step of detecting is performed 15 minutes after said contacting, or wherein the results of said detecting are obtained less than about 60 minutes after said thawing has begun.
Tigges discloses cotransfecting Chinese hamster ovary cells with the plasmid pNLK15 which harbors the firefly luciferase under control of the constitutive human elongation factor 1 alpha promoter (PhEF1a) and the plasmid pcDNA3.1-Xbp1(s) (see p.265, right column, first passage, p.267, left column, first passage). Tigges further teaches the use of a luminometer to detect the firefly luciferase activity (see p.266, left column, 1st paragraph).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have linked a constitutive promoter to the synthetic nucleotide encoding the reporter, as taught by Tigges, in the second expression vector of Li instead of using an inducible promoter and to have used a luminometer to measure luciferase activity, as taught by Tigges, to yield the claimed invention. Li does not suggest that the inducible promoter is critical to the claimed method and one of ordinary skill in the art would have a reasonable expectation of success using the constitutive promoter as the reporter will be constitutively expressed and the intracellular signaling of the reporter will not be compromised, absent evidence to the contrary. One of ordinary skill in the art would be motivated to use a luminometer as Tigges teaches its use in measuring luciferase activity and is a common technical practice in the relevant field.
Tigges does not disclose that the synthetic nucleotide sequence encodes a heterologous cAMP-binding protein fused to the modified reporter, not diluting the sample, that the nucleotide sequence that encodes the chimeric TSH receptor is at least 85% identical to the nucleotide sequence of SEQ ID NO: 1, that the step of contacting is performed less than about 5 minutes after said thawing, that the step of detecting is performed less than about 15 minutes after said contacting, or wherein the results of said detecting are obtained less than about 60 minutes after said thawing has begun.
Gray discloses a screening method for MALTI protease inhibitors utilizing a fused luciferase reporter system. Specifically, Gray teaches a cAMP-binding protein, wherein the cAMP-binding protein is fused to the reporter ("The reporter system utilized split luciferase technology (Promega GloSensor™), where a firefly luciferase enzyme is separated into two components by a cAMP-binding protein moiety. Binding of cAMP induces a conformational change that triggers light output." Para [0049]). The luciferase reporter disclosed by Li and the fused reporter disclosed by Gray are both capable of producing a detectable signal.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have used a luciferase reporter with a heterologous cAMP-binding protein fused to the luciferase reporter, as taught by Gray, in the method of Li to yield predictable results in signal detection associated with the reporter. Each of Li and Gray are directed to similar methods of screening utilizing a luciferase reporter to detect signaling. Thus, one of ordinary skill in the art would have a reasonable expectation of success detecting signals using the fused luciferase taught by Gray in the method of Li. The fused luciferase yielded reads on a modified luciferase as claimed.
Gray does not teach not diluting the sample, that the nucleotide sequence that encodes the chimeric TSH receptor is at least 85% identical to the nucleotide sequence of SEQ ID NO: 1 that the step of contacting is performed less than about 5 minutes after said thawing, that the step of detecting is performed less than about 15 minutes after said contacting, or wherein the results of said detecting are obtained less than about 60 minutes after said thawing has begun.
Brown teaches a method useful in the diagnosis of autoimmune diseases using a chimeric TSH receptor (Paras [0005]-[0007]). Brown teaches a nucleotide sequence of SEQ ID NO: 3 encoding a chimeric TSH receptor that is 100% identical to the nucleotide sequence of SEQ ID NO: 1 of the presently claimed invention, which is at least 85% identical as claimed (see sequence alignment in Appendix 1; Of Record).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to substitute the nucleotide sequence of SEQ ID NO: 3 encoding a chimeric TSH receptor, as taught by Brown, for the nucleotide sequence encoding a chimeric TSH receptor, as taught by Li, to arrive at the claimed invention. A skilled artisan would have been substituting one known nucleotide sequence encoding chimeric TSH receptors for another to obtain predictable results.
Brown does not teach the undiluted sample, that the step of contacting is performed less than about 5 minutes after said thawing, that the step of detecting is performed less than about 15 minutes after said contacting, or wherein the results of said detecting are obtained less than about 60 minutes after said thawing has begun.
However, Kohn teaches a method of detecting thyroid hormones using a transgenic cell wherein the step of contacting comprises contacting with an undiluted sample ("iii) an undiluted serum sample and a diluted serum sample from a patient suspected of having Graves' disease; b) contacting the undiluted serum sample and diluted serum sample with the cell line and the medium under conditions such that a reporter gene emits a detectable signal upon induction by a TSH receptor-specific stimulating auto-antibody” Para [0123]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used an undiluted sample, as taught by Kohn, in the method of Li to yield predictable results and arrive at the claimed invention. Each of Li and Kohn are directed to similar methods of detecting thyroid hormones in a sample using transgenic cells, each relying on thyroid stimulation hormone receptors. Thus, one of ordinary skill in the art would have a reasonable expectation of success in detecting thyroid hormones in an undiluted sample at least because Kohn teaches this.
Kohn does not teach that that the step of contacting is performed less than about 5 minutes after said thawing, that the step of detecting is performed less than about 15 minutes after said contacting, or wherein the results of said detecting are obtained less than about 60 minutes after said thawing has begun.
Brown2 teaches a method for detecting thyroid hormones in a sample using transgenic cells. Specifically, Brown2 teaches that the cells are not to be thawed until immediately prior to use in detecting in para [0164]. One of ordinary skill in the art would recognize that not thawing until immediately prior to use means that the cells must be used instantly after thawing without any intervening time. Thus, Brown2 teaching immediate detection reads on the step of contacting will occur less than 5 minutes after thawing.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to contact the cells immediately, as taught by Brown2, in the method taught by Li modified by Tigges, Gray, Brown, and Kohn as outlined above, to yield predictable results. Each of Li and Brown are directed to similar methods of detecting thyroid hormones using transgenic cells, each relying on thyroid stimulating hormone receptors for detection. Thus, one of ordinary skill in the art would have a reasonable expectation of success implementing using cells immediately after thawing in the method of Li.
Brown2 does not teach that the step of detecting is performed less than about 15 minutes after said contacting, or wherein the results of said detecting are obtained less than about 60 minutes after said thawing has begun.
Arena Pharmaceuticals teaches a method of detecting a signal from a luciferase reporter in a cell at least about 10 minutes after the cell is in contact with a test compound in para [0171]. Arena Pharmaceuticals teaches detection of a luciferase signal at least after about 10 minutes which satisfies detection in less than about 15 minutes. This is advantageous because the signal intensity is known in the art to decay over time, leading to worse readings (Ignowski - Fig. 3).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used Arena Pharmaceuticals’ step of detecting a luciferase signal within at least about 10 minutes in the method of Li to yield predictable results in intracellular signal detection. One of ordinary skill in the art recognizes that the signal intensity decays over time, as taught by Ignowski, which makes it advantageous to perform the detection in a timely manner and would have reasonable expectations of success doing so.
With regards to the limitation “wherein the results of said detecting are obtained less than about 60 minutes after said thawing has begun,” the method obviated by Li in view of Tigges, Gray, Brown, Kohn, Brown2, Arena Pharmaceuticals, and Ignowski would necessarily provide results within the claimed time constraints since Brown2 teaches the cells are thawed immediately prior to use in contacting and Arena Pharmaceuticals teaches detection of a luciferase signal at least after about 10 minutes. Thus, one of ordinary skill in the art would expect that the time from thawing to obtaining results from the step of detection is about 10 minutes, which is less than about 60 minutes after said thawing.
Regarding claim 19, Li teaches wherein the transgenic cells further comprise a substrate for the reporter ("In some embodiments, the TBI assay comprises using CHO-MC4 cells, cell growth medium, bTSH, Thyretain.TM. reaction buffer (Quidel Corp. & Diagnostic Hybrids, Inc., Ohio, USA), luciferase substrate and patient blood serum sample." Para [0049]).
Regarding claim 22, Li teaches a step of exposing the transgenic cells to the substrate for the reporter before the step of contacting ("measuring the level of expression of the reporter gene (e.g., by detecting bioluminescence resulting from luciferase enzyme activity) in the transgenic cells before the contacting and after the contacting," Para [0066]).
Regarding claim 24, Arena Pharmaceuticals teaches detection of a luciferase signal at least after about 10 minutes (see paragraph [0171]). This is advantageous because the signal intensity is known in the art to decay over time, leading to worse readings (Ignowski - Fig. 3).
Arena Pharmaceuticals does not teach wherein the step of detecting is performed less than 5 minutes after said contacting.
It would have been obvious to one of ordinary skill in the art, before the claimed invention, to have routinely optimized the time to detect the signal and arrive at less than 5 minutes after thawing. One of ordinary skill in the art would have recognized from Ignowski that delaying the detection time is deleterious to signal intensity since it decays over time and that the detection time of Arena Pharmaceuticals can be adjusted since they teach it is detected in about 10 minutes.
Regarding claim 25, Li teaches wherein the intracellular signal is detected from a composition comprising the transgenic cells and the sample ("and c) measuring the level of expression of the reporter gene in the first sample and in the second sample" Para [0005]).
Regarding claim 27, Li teaches wherein the step of contacting is performed at room temperature ("until just prior to use, at which time it may be removed and placed in a 25-37.degree. C. water bath to thaw and reach room temperature." Para [0078]).
Regarding claim 30, Li teaches wherein the step of contacting further comprises contacting the transgenic cells with a control thyroid-stimulating agent ("b) contacting the transgenic cells and the TSH with i) the control sample to produce a first sample, and ii) the test sample to produce a second sample," Para [0005]).
Regarding claim 31, Li teaches wherein the transgenic cells are contacted with the control thyroid-stimulating agent before the transgenic cells are contacted with the sample ("b) contacting the transgenic cells and the TSH with i) the control sample to produce a first sample, and ii) the test sample to produce a second sample," Para [0005]).
Regarding claims 32 and 33, Brown teaches the nucleotide sequence that encodes the chimeric TSH receptor has the nucleotide sequence of SEQ ID NO: 1 (100% identical) which is at least 95% identical, as discussed in the rejection of claim 18 above.
Therefore, Li in view of Tigges, Gray, Brown, Kohn, Brown2, Arena Pharmaceuticals, and Ignowski obviate the invention of claims 18-19, 22, 24, 25, 27, and 30-33.
Maintained Rejection: Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Li (US2013/0065252; Of Record) in view of Tigges (Metabolic Engin., 2006, Vol. 8(3); p.264-272; Of Record), Gray (WO2018/165385; Of Record), Brown (US2008/0187942; Of Record), Kohn (US2014/0120552; Of Record), Brown2 (US2013/0059312; Of Record), Arena Pharmaceuticals (US2008/0009551; Of Record) and Ignowski (Biotechnol. and Bioengin., 2004, Vol.86 (7); p. 827-834; Of Record), as applied to claims 18-19, 22, 24-25, 27, and 30-33 above, and further in view of Skidmore et al. (Animal Reprod. Sci., 2009, Vol. 113 (1-4), p.196-204; Of Record).
Regarding claim 26, Li, Tigges, Gray, Brown, Kohn, Brown2, Arena Pharmaceuticals, and Ignowski may not teach wherein at least 75% of the transgenic cells in the composition are intact at the time of detecting; however, Li teaches using cells immediately ("Freezer vials of cells should not be allowed to warm from their -80oC (or lower) storage temperature until immediately prior to thawing and use in the methods of the present invention, as cycling of the temperature may result in viability losses." Para [0164]). One of ordinary skill in the art will recognize that not thawing until immediately prior to use means that the cells must be used instantly after thawing with no time delays.
However, Skidmore teaches that freeze-thawing protocols with higher than 75% viability were known in the art before the effective filing date of the claimed invention (Table 1 – Skidmore). Skidmore teaches that only 12.5% of cells were dead after 7 days following thawing. Thus, Li’s method of using the cells immediately suggests that the cells are at least more than 87.5% intact.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the freeze-thawing methods taught by Skidmore in the method of Li to yield predictable results. Since Li teaches using the cells immediately after thawing, one of ordinary skill in the art would reasonably expect that the cell viability is over at least 87.5%, as taught by Skidmore above, post thawing.
Response to Arguments
Applicant's arguments filed 2/3/2026 have been fully considered but they are not persuasive.
In Applicant’s Remarks, see p.2, last paragraph,-p.3, 1st paragraph, Applicant argues none of the cited prior art in combination teach or suggest a transgenic cell stably expressing a reporter operably linked to a constitutive promoter as claimed. Applicant argues such modifications to Li would destroy the principle of operation in Li. Applicant further asserts only impermissible benefit of hindsight would permit such a modification to Li. This is not found persuasive. Specifically, Gray teaches a cAMP-binding protein, wherein the cAMP-binding protein is fused to the reporter ("The reporter system utilized split luciferase technology (Promega GloSensor™), where a firefly luciferase enzyme is separated into two components by a cAMP-binding protein moiety. Binding of cAMP induces a conformational change that triggers light output." Para [0049]). The luciferase reporter disclosed by Li and the fused reporter disclosed by Gray are both capable of producing a detectable signal. Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have used a luciferase reporter with a heterologous cAMP-binding protein fused to the luciferase reporter, as taught by Gray, in the method of Li to yield predictable results in signal detection associated with the reporter. Applicant has not demonstrated how the modification would destroy the principal of operation in Li and render the invention of Li inoperable.
In Applicant’s Remarks, see p.3, 2nd paragraph-p.4, 1st paragraph, Applicant asserts the claimed method permits unexpectedly rapid assessment of samples suspected of thyroid stimulating and/or thyroid blocking autoantibodies. Applicant further asserts a person of ordinary skill in the art would understand from the instant application that the utilization of separate expression of the modified luciferase reporter produces the reporter independently of the amount of antibodies present. Applicant further asserts no combination of the cited prior art suggests a method as presently claimed and a person of ordinary skill in the art would not expect the substantial reduction in total time. Applicant argues the Office has not provided any finding of fact establishing the prior art teaches or suggests methods in which separate expression vectors are used. This is not found persuasive. Applicant does not substantiate the claims made with regards to the Office action. The reduction in turn-around time is not an unexpected result as the prior art envisioned all structural aspects of the claimed invention. Specifically, Gray teaches a cAMP-binding protein, wherein the cAMP-binding protein is fused to the reporter ("The reporter system utilized split luciferase technology (Promega GloSensor™), where a firefly luciferase enzyme is separated into two components by a cAMP-binding protein moiety. Binding of cAMP induces a conformational change that triggers light output." Para [0049]). The luciferase reporter disclosed by Li and the fused reporter disclosed by Gray are both capable of producing a detectable signal. Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have used a luciferase reporter with a heterologous cAMP-binding protein fused to the luciferase reporter, as taught by Gray, in the method of Li to yield predictable results in signal detection associated with the reporter. Additionally, there are no lysing agents present in the method step of contacting taught by Li ("In some embodiments, the TBI assay comprises using CHO-MC4 cells, cell growth medium, bTSH, Thyretain.TM. reaction buffer (Quidel Corp. & Diagnostic Hybrids, Inc., Ohio, USA), luciferase substrate and patient blood serum sample." Para [0049]). The method obviated by Li in view of Tigges, Gray, Brown, Kohn, Brown2, Arena Pharmaceuticals, and Ignowski would necessarily provide results within the claimed time constraints since Brown2 teaches the cells are thawed immediately prior to use in contacting and Arena Pharmaceuticals teaches detection of a luciferase signal at least after about 10 minutes. Thus, one of ordinary skill in the art would expect that the time from thawing to obtaining results from the step of detection is about 10 minutes, which is less than about 90 minutes or less than about 60 minutes after said thawing. Therefore, the method obviated by the rejection set forth above would also result in an expected reduction in turn-around time from what was known in the prior art. Additionally, Li also embraces separate expression vectors and would be expected to comprise the features applicant argues, absent evidence to the contrary. Even more, the modified luciferase reporter taught by Gray in the rejection above teaches a cAMP-binding protein, wherein the cAMP-binding protein is fused to the reporter ("The reporter system utilized split luciferase technology (Promega GloSensor™), where a firefly luciferase enzyme is separated into two components by a cAMP-binding protein moiety. Binding of cAMP induces a conformational change that triggers light output." Para [0049]). Therefore, the method obviated by the rejection set forth above would also result in an expected reduction in turn-around time from what was known in the prior art.
In Applicant’s Remarks, see paragraph bridging pp.4-5, Applicant argues that Brown2 does not teach that the contacting step is performed in less than 5 minutes after thawing. This is not found persuasive. Brown2 teaches that the cells are not to be thawed until immediately prior to use in detecting in para [0164]. One of ordinary skill in the art would recognize that not thawing until immediately prior to use means that the cells must be used instantly after thawing without any intervening time. Thus, Brown2 teaches that the step of contacting will occur less than 5 minutes after thawing. One of ordinary skill in the art would recognize that thawing the cells stored in the freezer would result in a warming of the cells which Brown2 states should not be allowed until immediately prior to thawing and use in the methods of the present invention. Thus, the person of ordinary skill in the art would recognize it is to be avoided to allow the cells to sit between thawing and use, which involves contacting, in the method of detection.
In Applicant’s Remarks, see p.5, 1st paragraph,-p.6, 1st paragraph, Applicant argues that no combination of the cited prior art teaches or suggests a method involving a detecting step which is performed less than about 30 minutes after a contacting step, or a method wherein results of said detecting are obtained less than about 60 minutes after said thawing has begun. Applicant argues one of ordinary skill in the art looking to Arena Pharmaceuticals would extend the period of detection not reduce it. This is not found persuasive. While Arena Pharmaceuticals does disclose time periods greater than at least about 10 minutes, they do not preclude that detecting can be done in at least about 10 minutes which is within the claimed time range. Furthermore, one of ordinary skill in the art would recognize there is room for adjusting the time frame of detection by what is disclosed in Arena Pharmaceuticals as the term “about” is used. Thus, the claimed invention recites features that were recognized in the prior art and well within the purview of an ordinarily skilled artisan. Furthermore, Ignowski demonstrates that signal intensity is known to decay over time, leading to worse readings (Ignowski – Fig. 3). Thus, the person of ordinary skill in the art would have found it obvious to reduce the time of detection when looking to Arena Pharmaceuticals and Ignowski.
Conclusion
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.
/J.P.S./ Examiner, Art Unit 1651
/MELENIE L GORDON/ Supervisory Patent Examiner, Art Unit 1651