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 .
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.
Priority
This application is a U.S. National Stage (371) application of PCT/US2020/025296 filed on 03/27/2020 which claims priority to U.S. Provisional Application No. 62/951,546 filed on 12/20/2019 and to U.S. Provisional Application No. 62/824,917 filed on 03/27/2019.
Claim Status
Claims 1-2 are previously presented. Claims 3-16 and 18-19 are original. Claims 17 and 20-200 are cancelled at the Applicant’s request.
Thus, claims 1-16 and 18-19 are pending and are under examination.
Maintained Rejections
Claim Rejections - 35 USC § 103
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 (PHOSITA) 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.
Claims 1, 6-9 and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Baranov et al. (US 7,767,407 B2) in view of Sutkowski et al. (US 2013/0115674 A1), Qian et al. (US 2022/0280469 A1, priority to 01/23/2019), Zunder et al. (Nature protocols, Vol. 10, No.2) and Matos et al. (Journal of Investigative Dermatology, (2017) 137, e31-e38).
Regarding claim 1, the claim recites:
“A panel for elemental analysis, comprising:
a plurality of conjugated antibodies, wherein each of the plurality of conjugated antibodies is tagged with a distinct element tag, wherein each distinct element tag is distinguishable based on its isotopic composition, and wherein the plurality of conjugated antibodies is in a lyophilized mixture, and
a lyophilized intercalator, wherein the lyophilized intercalator is included in the lyophilized mixture, and wherein the intercalator comprises iridium or rhodium”.
Regarding claim 1, Baranov teaches an elemental analysis panel or array (Column 4, lines 42-45).
Baranov teaches a plurality of tagged biologically active affinity materials or conjugated antibodies (Column 17, lines 5-12; column 44, lines 10-17).
Baranov teaches that each of the plurality of conjugated antibodies is tagged with a distinct element tag (Column 17, lines 5-12; column 44, lines 10-17).
Baranov teaches that each distinct element tag is distinguishable based on its isotopic composition (Column 43, claim 15).
Baranov provides standards in lyophilized form (Column 21, lines 1-6).
Regarding claim 6, Baranov teaches that each distinct element tag comprises a plurality of elemental atoms of one isotope (Column 43, claim 15).
Regarding claim 7, Baranov teaches that at least two conjugated antibodies of the plurality of conjugated antibodies are tagged with distinct element tags having different isotopes of a single element (Column 44, claim 22).
Regarding claim 8, Baranov teaches that the elemental analysis panel further comprises a biomolecule coupled to an additional element tag (Column 5, lines 13-31).
Baranov teaches that the biomolecule is not an antibody (Column 5, lines 13-31).
Baranov teaches that the additional element tag is distinguishable from each distinct element tag based on its isotopic composition (Column 5, lines 13-31).
Regarding claim 9, Baranov teaches that elemental analysis panel further comprises a non-antibody metal-containing moiety such as an aptamer complexed to a metal element comprising a metal isotope that is distinguishable from each distinct element tag based on its isotopic composition (Column 4, lines 32-41; column 7, lines 29-38).
Regarding claim 18, Baranov teaches that the elemental analysis panel further comprises a lyophilized calibration material (Columns 20-21, lines 66-67 of column 20 and lines 1-6 of column 21).
Baranov teaches that the lyophilized calibration material comprises known quantities of one or more known isotopes or element that would not interfere with elemental analysis (Column 9, lines 50-57, “The kits may also include standards … Further, the element may include more than one element, isotope or atom of an isotope and may include a different number of atoms of each isotope”; columns 20-21, lines 66-67 of column 20 and lines 1-6 of column 21).
Baranov teaches that the lyophilized calibration material is included in the lyophilized mixture (Columns 20-21, lines 66-67 of column 20 and lines 1-6 of column 21).
Regarding claim 19, Baranov teaches that the elemental analysis panel further comprises a supplemental reagent such as dilution buffers, elution buffers, wash buffers and assay buffers (Column 9, lines 50-51).
Baranov teaches that the supplemental reagent is usable for conducting an assay using the plurality of conjugated antibodies (Column 10, lines 20-30). Although Baranov does not explicitly teach that the supplemental material is lyophilized, an artisan would be motivated to lyophilize the supplemental material to increase its stability as it has been done with standards.
Regarding claim 1, Baranov does not teach that the plurality of conjugated antibodies is in a lyophilized mixture.
Baranov does not teach that a lyophilized intercalator is included in the lyophilized mixture of conjugated antibodies.
Baranov does not teach that the intercalator comprises iridium or rhodium.
Regarding claim 1, Sutkowski teaches that the plurality of conjugated antibodies is in a lyophilized mixture (Page 42, [0315]). Sutkowski teaches using cisplatin as an intercalator with an antibody (Page 42, [0307]).
Regarding claim 1, Qian teaches lyophilizing cisplatin to improve its stability and release rate (Page 11, [0124]; page 12-13, [0133-0134]).
Regarding claim 1, Zunder teaches that the intercalator comprises iridium (Page 322, left column, first paragraph).
Regarding claim 1, Matos teaches that iridium is known to bind DNA with high affinity allowing for the detection of all DNA containing cells and aiding in the identification of single-cell events (Page e35, left column, second paragraph).
It would have been obvious for a PHOSITA before the effective filing date of the application to combine the cisplatin and the lyophilized conjugated antibodies of Sutkowski with the elemental analysis panel of Baranov to improve the elemental analysis array for detection and measurement of element-tagged biologically active materials and element-tagged competition analytes because Sutkowski showed how to use antibodies and an intercalator to diagnose and treat malignant and non-malignant diseases (Abstract; page 42, [0307]). The skilled artisan would have been more motivated to combine the lyophilized cisplatin of Qian with the methods of Sutkowski and Baranov because Qian further showed how to increase the stability and the release rate of an intercalator such as cisplatin by lyophilizing it (Page 11, [0124]; page 12-13, [0133-0134]). The skilled artisan would have been motivated to combine the iridium intercalator of Zunder with the methods of Baranov, Sutkowski and Qian because Zunder showed how to label individual cell samples with unique combinatorial barcodes (Abstract). Furthermore, iridium is known to bind DNA with high affinity allowing for the detection of all DNA containing cells and aiding in the identification of single-cell events as it has been noted by Matos (Page e35, left column, second paragraph). A skilled artisan would been further motivated to combine the above methods to provide a kit with a high level of stability for its components. A PHOSITA would have had a reasonable expectation of success in combining the methods of Baranov, Sutkowski, Qian, Zunder and Matos because the methods are all based on using antibodies for diagnostic and treatment purposes.
It would have been obvious for a PHOSITA to further lyophilize the tagged antibodies and intercalators and include in the kit of Baranov to maintain the stability of the used antibodies and intercalators.
Claims 2-5 and 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Baranov et al. (US 7,767,407 B2), Sutkowski et al. (US 2013/0115674 A1), Qian et al. (US 2022/0280469 A1, priority to 01/23/2019), Zunder et al. (Nature protocols, Vol. 10, No.2) and Matos et al. (Journal of Investigative Dermatology, (2017) 137, e31-e38) as applied to claims 1 above, and further in view of Tanner et al. (Pure Appl. Chem., Vol. 80, No. 12, pp. 2627–2641, 2008).
Regarding claim 2, the claim recites:
“The panel of claim 1, wherein the plurality of conjugated antibodies includes two or more antibodies that are raised against two or more of the group consisting of Cd45, CD45RA, CD45RO, Cd 123, CD4, CD8a, CD11C, CD57, CXCR3, CD185, CD38, CD56, CD3, CD20, CD66b, HLA-DR, IgD, CD27, CD28, CD127, CD19, CD16, CD161, CD194, CD25, CD294, CD197, CD14, CCR6, and TCR δγ”.
Regarding claims 1-5 and 10-12 Baranov, Sutkowski, Qian, Zunder and Matos teach or suggest all of the limitations of the claims as discussed above.
Additionally, regarding claim 5, Sutkowski teaches that the plurality of conjugated antibodies is in a lyophilized mixture (Page 42, [0315]).
Regarding claim 2, Baranov fails to teach that the plurality of conjugated antibodies includes two or more antibodies from the group consisting of CD45, CD45RA, CD45RO, CD 123, CD4, CD8a, CD11C, CD57, CXCR3, CD185, CD38, CD56, CD3, CD20, CD66b, HLA-DR, IgD, CD27, CD28, CD127, CD19, CD16, CD161, CD194, CD25, CD294, CD197, CD14, CCR6, and TCR δγ.
Regarding claim 3, Baranov does not teach that a majority of the conjugated antibodies are specific to a cell type in human peripheral blood.
Regarding claim 4, Baranov does not teach that a majority of the conjugated antibodies are specific to a cell surface marker.
Regarding claim 5, Baranov does not teach that the plurality of conjugated antibodies comprises ten or more conjugated antibodies in the lyophilized mixture. Baranov does not teach that the plurality of
Regarding claim 10, Baranov does not teach that each distinct element tag comprises a metal element having an atomic mass greater than 80 amu.
Regarding claim 11, Baranov does not teach that each distinct element tag comprises a chelated metal.
Regarding claim 12, Baranov does not teach that each distinct element tag comprises an element that is not endogenous to human peripheral blood.
Regarding claim 2, Tanner teaches that the plurality of conjugated antibodies includes two antibodies that are respectively against CD45 and CD38 (Page 2635, Fig. 5, “CD45”, “CD38”; page 2635, second paragraph, “Also presented here for the first time are data obtained with the prototype FC-MS instrument … -CD45-159Tb, -CD38-165Ho”).
Regarding claim 3, Tanner teaches that a majority of the conjugated antibodies are specific to a cell type in human peripheral blood of a leukemia patient from the Quebec Leukemia Cell Bank (BCLQ) (Page 2635, Fig. 5, “Simultaneous 20-parameter analysis of cell surface antigens in bulk mode… a patient sample, were separately probed with a 20-member antibody panel tagged with the enriched isotopes shown.”).
Regarding claim 4, Tanner teaches that a majority of the conjugated antibodies are specific to a cell surface marker (Page 2634, last paragraph, “We report here for the first time the results of 20-parameter measurements in the bulk analysis mode. KG1a cells were stained for 20 cell surface markers… Results for a patient sample, indicated in Fig. 5 as BCLQ (Quebec Leukemia Cell Bank), show further suppression of the CD34 marker and other characteristic antigen expression differences”).
Regarding claim 5, Tanner teaches that the plurality of conjugated antibodies comprises ten or more conjugated antibodies (Page 2635, Fig. 5, “Simultaneous 20-parameter analysis of cell surface antigens in bulk mode”).
Regarding claim 10, Tanner teaches that each distinct element tag comprises a metal element having an atomic mass greater than 80 amu such as a lanthanide isotope (Page 2632, second paragraph, “After linking to the antibody, a solution of a lanthanide chloride is added, resulting in the strong chelation of the lanthanide isotope”).
Regarding claim 11, Tanner teaches that each distinct element tag comprises a chelated metal (Page 2632, second paragraph, “After linking to the antibody, a solution of a lanthanide chloride is added, resulting in the strong chelation of the lanthanide isotope”).
Regarding claim 12, Tanner teaches that each distinct element tag comprises an element that is not endogenous to human peripheral blood such as lanthanides (Page 2632, second paragraph, “After linking to the antibody, a solution of a lanthanide chloride is added, resulting in the strong chelation of the lanthanide isotope”; page 2632, Fig. 2, “The unlabeled Ab-tag can be stored and labeled with enriched lanthanide elements prior to application to the sample”).
It would have been obvious for a PHOSITA before the effective filing date of the application to combine Tanner’s method for detecting surface markers of cells by elemental analysis with the methods of Baranov, Qian, Sutkowski, Zunder and Matos because Tanner suggested using their method in health and disease detection (Page 2628, fourth paragraph, “the detailed biomarker signature of individual cells allows a diseased (or healthy) cell … it can be projected that diagnosis of disease will be able to be performed earlier and with better confidence …”). A skilled artisan would have been further motivated to combine the above methods to provide a diagnostic kit with a high level of stability for its components. A PHOSITA would have had a reasonable expectation of success in combining the methods of Baranov, Qian, Sutkowski, Zunder, Matos and Tanner because the methods are based on using antibodies for diagnostic and treatment purposes.
It would have been obvious for a PHOSITA to further lyophilize the tagged antibodies against markers of cells and include in the kit of Baranov to better diagnose a disease.
Claims 13-16 are rejected under 35 U.S.C. 103 as being unpatentable over Baranov et al. (US 7,767,407 B2), Sutkowski et al. (US 2013/0115674 A1), Qian et al. (US 2022/0280469 A1, priority to 01/23/2019), Zunder et al. (Nature protocols, Vol. 10, No.2) and Matos et al. (Journal of Investigative Dermatology, (2017) 137, e31-e38)as applied to claims 1 above, and further in view of Shrawat et al. (WO 2014/060962 A1).
Regarding claims 13-16, Baranov, Sutkowski, Qian, Zunder and Matos teach or suggest all of the limitations of the claims as discussed above.
Regarding claim 13, Baranov fails to teach that the panel or a composition has a moisture content that is at or less than 5% by weight.
Regarding claim 14, Baranov fails to teach that the panel has a moisture content that is at or less than 3% by weight.
Regarding claim 15, Baranov fails to teach that the panel has a moisture content that is at or less than 1 % by weight.
Regarding claim 16, Baranov fails to teach that the panel has a moisture content that is at or between 0.05 and 1 % by weight.
Regarding claim 13, Shrawat teaches that the panel or a composition has a moisture content that is at or less than 5% by weight (Page 3, sixth paragraph, “wherein said composition is having moisture content less than 5% w/w”; page 4, third paragraph, “wherein a moisture content of the formulation is preferably less than about 5% by weight”).
Regarding claim 14, Shrawat teaches that the panel has a moisture content that is at or less than 3% by weight (Page 3, sixth paragraph, “wherein said composition is having moisture content less than 5% w/w”; page 4, third paragraph, “wherein a moisture content of the formulation is preferably less than about 5% by weight”).
Regarding claim 15, Shrawat teaches that the panel has a moisture content that is at or less than 1 % by weight (Page 3, sixth paragraph, “wherein said composition is having moisture content less than 5% w/w”; page 4, third paragraph, “wherein a moisture content of the formulation is preferably less than about 5% by weight”).
Regarding claim 16, Shrawat teaches that the panel has a moisture content that is at or between 0.05 and 1 % by weight (Page 3, sixth paragraph, “wherein said composition is having moisture content less than 5% w/w”; page 4, third paragraph, “wherein a moisture content of the formulation is preferably less than about 5% by weight”).
It would have been obvious for a PHOSITA before the effective filing date of the application to combine the method of maintaining a low level of moisture in the reagents of Shrawat with the methods of Baranov, Sutkowski, Qian, Zunder and Matos because Shrawat noted that it will maintain the stability of reagents (Page 3, sixth paragraph; page 12, first paragraph). A skilled artisan would have been further motivated to combine the above methods to provide a diagnostic kit with a high level of stability for its components. A PHOSITA would have had a reasonable expectation of success in combining the methods of Baranov, Qian, Shrawat, Sutkowski, Zunder and Matos because the methods are all based on using antibodies for diagnostic and treatment purposes.
It would have been obvious for a PHOSITA to further lyophilize the tagged antibodies and maintain a low level of moisture to increase the stability of reagents that can be used in the kit of Baranov to avoid the deterioration of reagents, antibodies and intercalators.
Response to Arguments
Applicant's arguments filed 12/18/2025 have been fully considered but they are not persuasive.
The Applicant argued that the motivations identified in the Office action are based upon misinterpretation of the prior art. The Applicant further argued that none of the prior art discloses or suggests a mixture of components in lyophilized form, much less the specific mixture recited in claim 1, and the prior art discloses only purified individual compounds in lyophilized form.
This argument is not persuasive because in response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In the instant case, it is well established that lyophilizing reagents increases their stability and suitability (Qian: Page 11, [0124] and page 12-13, [0133-0134]; Sutkowski: page 42, [0315]). When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation, § 103 may bar its patentability. When considering obviousness of a combination of known elements, the operative question is thus “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (MPEP 2141. I.). And in the instant case, the methods of Baranov, Sutkowski, Qian, Zunder and Matos are all based on using antibodies for diagnostic and treatment purposes. Thus, a skilled artisan would have been further motivated to combine the above methods to provide a kit with a high level of stability for its components.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 OMAR RAMADAN whose telephone number is (571)270-0754. The examiner can normally be reached Monday-Friday 8:30 am - 5:00 pm.
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/OMAR RAMADAN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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