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 the U.S. application filed on 05/28/2024 that claims priority to Foreign Application No. IN202441018279 filed on 03/13/2024.
The Applicant is required to provide a certified copy of the foreign priority application required by 37 CFR 1.55.
Furthermore, the Applicant cannot rely upon the certified copy of the foreign priority application to overcome any prior art rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Thus, for purposes of applying prior art, claims 1-10 are subject to a priority date of 05/28/2024.
Specification
The title of the instant application recites: “Diagnostichome Kit Todetectmidkine Levelin Blood”. The following title is suggested: “Diagnostic Home Kit to Detect Midkine Level in Blood”. Appropriate correction is required.
The specification is objected to because of the following informalities: the specification recites “wherein the projected end is immobilized by a plurality of Anaplastic Lymphoma Kinase (ALK) receptors” and it is not clear how will the projected end of the biosensor be immobilized by the ALK receptor (Page 4, first paragraph; page 7, first paragraph; page 9, [0035]). A possible correction is to recite “wherein a plurality of Anaplastic Lymphoma Kinase (ALK) receptors are immobilized on the projected end”. Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities: the claim recites “wherein the projected end is immobilized by a plurality of Anaplastic Lymphoma Kinase (ALK) receptors” and it is not clear how will the projected end of the biosensor be immobilized by the ALK receptor. A possible correction is to recite “wherein a plurality of Anaplastic Lymphoma Kinase (ALK) receptors are immobilized on the projected end”. Appropriate correction is required.
Claim Interpretation
Claim 1 recites “A diagnostic home kit to detect a level of midkine in a blood sample”. However, the term “home ”is drawn to the intended use of the kit. The kit is evaluated on its structural and functional components, in particular, the piezoelectric cantilever biosensor that has immobilized Anaplastic Lymphoma Kinase (ALK) receptor, and not on the location where it is used.
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 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 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Stoica et al. (JBC, Volume 277, Issue 39, 27 September 2002, Pages 35990-35998) in view of Mutharasan et al. (US 2009/0078023 A1), Naresh et al. (Sensors 2021, 21, 1109, Pages 1-35) and Heidecke et al. (US 2019/0250172 A1).
Claim 1 recites:
“A diagnostic home kit to detect a level of midkine in a blood sample, the diagnostic home kit
comprises:
an analyte receiver to receive the blood sample;
a cantilever biosensor having:
a fixed end; and
a projected end, protruding from the fixed end, coated with a piezoelectric material,
wherein the projected end is immobilized by a plurality of Anaplastic Lymphoma Kinase
(ALK) receptors configured to attach the midkine from the received blood sample, such
that the piezoelectric material transduces a signal corresponding to the attached midkine;
an amplifier, coupled to the fixed end of the cantilever biosensor, to receive and amplify
the transduced signal;
a signal processor to process the amplified signals to determine the level of midkine in the
received blood sample”.
Regarding claim 1, Stoica teaches that Anaplastic Lymphoma Kinase (ALK) receptors are configured to bind to midkine (Abstract; page 35993, “MK binding to anaplastic lymphoma kinase (ALK) in intact cells”, “A, saturation binding of 35S-MK to 32D/ALK”; page 35994, right column, first paragraph, “From this series of experiments we conclude that MK and PTN bind to the same receptor, albeit with ~5-fold different affinities”; page 35996, FIG.5, “B, ALK phosphorylation in WI-38 human fibroblasts by MK. WI-38 cells were treated with control medium and with MK (10 ng/ml) without and with preincubation with antibodies to MK or to PTN”).
Regarding claim 9, Stoica teaches that a buffer is received by the analyte receiver to wash away the attached midkine from the plurality of ALK receptors [page 35591, right column, first paragraph, “was loaded onto 1-ml heparin-Sepharose columns (Amersham Biosciences) and washed, and the bound proteins were eluted with a step gradient of 3 ml each of 0.4, 0.9, and 2.0 M NaCl in 10 mM Tris buffer (pH 7.5)”].
Regarding claim 10, Stoica teaches an exit port to pull and egress out at least one of: residual blood, the washed away midkine, and the buffer, wherein the buffer corresponds to a Tris-Buffered Saline (TBS) [page 35591, right column, first paragraph, “and the bound proteins were eluted with a step gradient of 3 ml each of 0.4, 0.9, and 2.0 M NaCl in 10 mM Tris buffer (pH 7.5)”].
Regarding claim 1, Stoica does not teach an analyte receiver to receive the blood sample. Also, Stoica does not teach cantilever biosensor having a fixed end. And Stoica does not teach that the cantilever biosensor further has a projected end, protruding from the fixed end and coated with a piezoelectric material. Stoica does not further teach an amplifier that is connected to the biosensor to receive and amplify the transduced signal. And Stoica does not teach a signal processor to process the amplified signals to determine the level of analyte in the received blood sample. Stoica also does not teach detecting a level of midkine in a blood sample.
Regarding claim 2, Stoica does not teach an output display unit to display the level of analyte in the blood sample.
Regarding claim 3, Stoica does not teach an analyzer to determine a disease based on the level of midkine in the received blood sample.
Regarding claim 4, Stoica does not teach that the determined disease is Atherosclerosis and Myocardial Infarction when the level of midkine is in a range of 50-200 ng/dL and 500-1000 ng/dL, respectively.
Regarding claim 5, Stoica does not teach that the analyzer identifies the level of midkine in a range of 0 to 0.625 ng/dL as normal.
Regarding claim 6, Stoica does not teach a network module to connect with a communication network; and transmit at least one of: the level of analyte and the determined disease to a user device
associated with a user.
Regarding claim 7, Stoica does not teach that the user corresponds to at least one of: a patient, a doctor, a guardian, a healthcare specialist, and a health enthusiast.
Regarding claim 8, Stoica does not teach the user’s device corresponds to at least one of: a mobile phone, a tablet, a computer, a laptop, a Personal Digital Assistant (PDA), a smartwatch, a smart band, and a customized healthcare device.
Regarding claim 1, Mutharasan teaches an analyte receiver to receive the blood sample [0079-0080]. Mutharasan further teaches a cantilever biosensor having a fixed end (Sheet 20 of 23, Figure 20, “200”, “Expose Piezoelectric Cantilever Sensor to Medium”; [0006]; [0072]). And Mutharasan teaches that the cantilever biosensor further has a projected end, protruding from the fixed end and coated with a piezoelectric material [0049-0050].
Regarding claim 6, Mutharasan teaches that the biosensor comprises a network module to connect with a communication network and to transmit the level of analyte and the determined disease to a user device associated with a user [0041].
Regarding claim 1, Naresh teaches an amplifier that is connected to the biosensor to receive and amplify the transduced signal (Page 4, first paragraph, “The electrical signals obtained from the transducer are amplified”; page 4, Figure 2, “Amplifier”). Naresh further teaches a signal processor to process the amplified signals to determine the level of analyte (Page 4, first paragraph, “The transduced signal is processed and prepared for the display”; page 4, Figure 2, “Processor”).
Regarding claim 2, Naresh teaches an output display unit to display the level of analyte (Page 3, second paragraph, “A typical biosensor comprises (a) an analyte, (b) bioreceptor, (c) transducer, (d) electronics, and (e) display (Figure 2)”; page 4, Figure 2, “Display”).
Regarding claim 8, Naresh teaches that the user device corresponds to at least one of: a mobile phone, a tablet, a computer, a laptop, a Personal Digital Assistant (PDA), a smartwatch, a smart band, and a customized healthcare device (Page 4, “Display: The display unit is composed of a user interpretation system, such as a computer or a printer that generates the output so that the corresponding response can be readable and understandable by the user”; page 4, Figure 2, “display (PC or printer)”).
Regarding claim 1, Heidecke teaches detecting a level of midkine in a blood sample (Abstract, [0056]; [0074]).
Regarding claim 3 Heidecke teaches to determine a disease based on the level of midkine in the received blood sample (Abstract; [0053]).
Regarding claim 4, Heidecke teaches that the determined disease is Atherosclerosis and Myocardial Infarction ([0017]; [0053]; [0120]; [0125]). Regarding claim 5, Heidecke teaches comparing the levels of midkine to normal values [0030].
Regarding claim 7, Heidecke teaches that the user corresponds to at least one of: a patient, a doctor, a guardian, a healthcare specialist, and a health enthusiast [0088].
It would have been obvious for a PHOSITA before the effective filing date of the application to coat the piezoelectric cantilever biosensor of Mutharasan with the Anaplastic Lymphoma Kinase (ALK) receptors of Stoica to detect the binding of midkine because Mutharasan noted the ability to measure low concentration of a biomarker in blood rapidly, inexpensively, and directly without the need to use labeled reagents [0079]. A skilled artisan would have been further motivated to combine the technical modifications of Naresh’s biosensor with the combined methods of Mutharasan and Stoica because Naresh teaches the ability to quantify and display the quantified analyte in a convenient manner for the user (Page4, Figure 2, “Schematic diagram of typical biosensor consisting of bioreceptor, transducer, electronic system (amplifier and processor), and display (PC or printer)”). A skilled artisan would have been motivated to combine the cardiovascular disease predictive model of Heidecke with the combined methods of Naresh, Mutharasan and Stoica because Heidecke found that midkine levels are indicative of cardiovascular diseases and morbidity [0007]. A PHOSITA would have had a reasonable expectation of success in combining the methods of Heidecke, Naresh, Mutharasan and Stoica based on the methods being in the field of detecting a ligand.
It would have been obvious for a PHOSITA to modify the piezoelectric cantilever biosensor of Mutharasan with Stoica’s ALK receptors and Naresh’s display unit to measure midkine levels and to predict the cardiovascular outcomes of a patients as shown by Heidecke.
Regarding claims 4-5, while Heidecke teaches determining the diseases of Atherosclerosis and Myocardial Infarction ([0017]; [0053]; [0120]; [0125]) and provide a range of midkine of 0.02-3.61 ng/ml for comparison [0107], Heidecke teaches that serum midkine levels in healthy subjects are mostly determined within a narrow range that depends on the applied detection system [0006]. And thus, it will be routine optimization to reach to the ranges of the instant application, and the claims are a clear example of routine optimization within the prior art conditions or through routine experimentation. The midkine ranges of 50-200 ng/dL and 500-1000 ng/dL of claim 4 are clear examples for optimizing midkine ranges for predicting the outcome of a particular disease as compared to a normal midkine range of 0-0.625 ng/dL of claim 5.
In order to properly support a rejection on the basis that an invention is the result of "routine optimization", the examiner must make findings of relevant facts, and present the underpinning reasoning in sufficient detail. The articulated rationale must include an explanation of why it would have been routine optimization to arrive at the claimed invention and why a person of ordinary skill in the art would have had a reasonable expectation of success to formulate the claimed range. See In re Stepan, 868 F.3d 1342, 1346, 123 USPQ2d 1838, 1841 (Fed. Cir. 2017). See also In re Van Os, 844 F.3d 1359,1361,121 USPQ2d 1209, 1211 (Fed. Cir. 2017) ("Absent some articulated rationale, a finding that a combination of prior art would have been ‘common sense’ or ‘intuitive’ is no different than merely stating the combination ‘would have been obvious.’"); Arendi S.A.R.L. v. Apple Inc., 832 F.3d 1355, 1362, 119 USPQ2d 1822 (Fed. Cir. 2016) ("[R]eferences to ‘common sense’ … cannot be used as a wholesale substitute for reasoned analysis and evidentiary support … ."). In the instant case, a skilled artisan would have been motivated to combine the methods of Heidecke, Naresh, Mutharasan and Stoica and to optimize midkine ranges for different disease outcomes as shown by Heidecke ([0017]; [0025]; [0030]; [0053]; [0120]; [0125]). Heidecke teaches that each assay result obtained for midkine is compared to a “normal” value, or a value indicating a particular disease or outcome and to establish a threshold for comparison [0030].
Conclusion
No claims are allowed.
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/OMAR RAMADAN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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