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 .
DETAILED ACTION
Claims 13-26 are pending in the application. Claims 13-26 are rejected.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 November 18th, 2025 has been entered.
Response to Amendment / Argument
Objections and rejections made in the previous Office Action have been overcome by Applicant's amendments to the claims. Therefore, arguments pertaining to these objections and rejections will not be addressed with the exception of the double patenting rejection arguments that would pertain to the rejections below. Applicant states the “Office Action offers no more than conclusory statements that the claimed invention is obvious over the compound claims recited in the ‘837 patent.” The rationale is the same as found in the 103 rejections. Applicant refers to In re Kaplan that refers to a case where “a mere variation of that invention which would have been obvious to those of ordinary skill in the relevant art” which is the case here. The fact that the claims of the patents alone do not spell out the instantly claimed invention does not mean that the rejections are flawed since the rejections rely on the teachings of the references cited under 35 USC 103.
Drawings
The drawings are objected to because Figures 3 and 4 contain illegible structures. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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.
Claim(s) 13-21, 25 and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent PGPub No. 2014/0011219 A1 by Belle et al. in view of Mohy Eldin et al. Journal of Applied Polymer Science 2012, 125, 1724-1735.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Belle et al. teach (title) “Grafted dinuclear metal complexes, and use thereof as cellular microparticle sensors”. Belle et al. teach on page 1 that the terms “cellular microparticle” and “cellular microvesicle” may be used interchangeably (paragraph [0002]). Regarding utilities, the prior art teaches the following on page 5:
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The prior art generally teaches applicability to characterization of cellular microparticles for diagnosis of diseases. Regarding steps, the prior art teaches the following on page 5:
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The steps above refer to contacting a sample of biological fluid followed by capturing corresponding to the first step of instant claim 21 when applied to disease diagnosis.
As examples of complexes, Belle et al. teach the following complex on page 8:
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The complex above corresponds to formula (I) of instant claim 13 where Y is H, M is Zn+2 (embraced by claim 16), X is -CH2-NHC(O)R-NH2 where R is C5 alkyl and each n is 1 (embraced by claim 17). The structure above is the second recited structure in instant claim 18. The prior art further teaches immobilization of the complex (corresponding to grafting) on page 3 (paragraphs [0077]-[0085]). The steps include “[0078] activation of a solid support, [0079] immobilisation of a compound having formula (I) or (II) as defined here above on the surface of the activated support”. The prior art teaches in paragraph [0083]: “The activation of the support may be carried out by conventional methods, such as, for example, by using polyglutaraldehyde.” The prior art further teaches in paragraph [0084]: “During the immobilisation step, the compound having formula (I) or (II) binds to the activated support by forming covalent bonds.” As an example of a type of surface, Example 5 of the prior art (page 8) teaches the use of polyvinyl chloride. The prior art teaches contacting the support with a sample containing microvesicles in paragraph [0170] (page 8 of the prior art).
As an additional example, the prior art teaches the following complex on page 6:
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The complex above corresponds to formula (I) of instant claim 13 where Y is H, M is Zn+2 (embraced by claim 16), X is –(CH2)m-NH2 where m is 1 (embraced by claim 17) and each n is 1. The structure above is the first recited structure in instant claim 18. The prior art teaches analogous immobilization on a glutaraldehyde modified microtiter plate followed by exposure to microvesicles and characterization thereof.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art does not explicitly teach that the metal complexes were covalently attached to solid supports or that in the case of PVC, the solid support was prefunctionalized with ethylene diamine.
The prior art further does not teach explicit embodiments embraced by instant claims 19-21 involving contacting with a sample from a subject (where the step of obtaining the fluid from a subject is actually performed).
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2141.02)
Regarding the use of covalent attachment, Belle et al. teach the use of glutaraldehyde in paragraph [0168] and further teach forming covalent bonds in paragraph [0084]. While the prior art does not teach that covalent attachment occurs, a person having ordinary skill in the art would have been familiar with the use of glutaraldehyde to modify PVC surfaces for covalent attachments. Mohy Eldin et al. teach the need to functionalize PVC as follows on page 1724:
[…] Suitable functional groups are essential to conduct such immobilization techniques, since PVC has no functional groups in its structure, so chemical modification was carried out to introduce proper functional groups. […]
The authors further teach on page 1725:
[…] On the other hand, another simple technique using the aminoalkylation reaction with diamine has been presented.42 This technique depends on the reaction between the available chlorine atoms on the PVC surface and the amine groups of diamine. The introduced amine groups were further activated using a symmetric coupling agent, glutaraldehyde (GA), which finally covalently bound with enzyme. The mechanism of PVC modification, activation, and immobilization with the enzyme is presented in Scheme 1. […]
Scheme 1 depicts the corresponding steps:
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The prior art teaches reaction of ethylene diamine followed by glutaraldehyde. A person having ordinary skill in the art in practicing the general teachings of Belle et al. would have at least been motivated to test known methods of immobilizing materials on PVC (as recited in instant claims 14 and 15) including the method of Mohy Eldin et al., which corresponds to the steps of instant claims 25 and 26.
Regarding application of covalently modified sensors, at least since the prior art teaches utility in the diagnosis of disease, a person having ordinary skill in the art would have been motivated to contact samples obtained from subjects according to the nested product-by-process limitation of instant claim 19 using sensors discussed above. Furthermore, paragraph [0113] of the prior art teaches a step corresponding to characterization of captured microparticles as required by instant claim 20.
Regarding instant claim 21, Belle et al. teach the following on page 1:
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The prior art generally teaches that microparticles are markers for disease where instant claim 21 only requires “detection of the presence or absence of a marker associated with said disease,” such that performing the methods of the prior art attempting to detect the microparticles would meet the requirements of claim 21.
Claim(s) 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent PGPub No. 2014/0011219 A1 by Belle et al. in view of Mohy Eldin et al. Journal of Applied Polymer Science 2012, 125, 1724-1735, as applied to claims 13-21, 25 and 26 above, and in further view of Vajen et al. Thromb. Haemost. 2015, 114, 228-235.
Claim 22 further requires detecting the presence or absence of, for instance, CD41 “for the diagnosis of a diabetic nephropathy”. The limitation of “for the diagnosis” is a considered a type of intended use or intended outcome since it would embrace a mental step of making inferences based detecting the presence or absence of CD41. Furthermore, a person having ordinary skill in the art in seeking to apply the general methods of Belle et al. to diagnosis of metabolic disorders (taught in paragraph [0006]) or diabetes (taught in paragraph [0111]) would have been familiar with microvesicle markers correlating to such disease states. Vajen et al. teach the following on page 231:
[…] Increased levels of PMVs identified in patients with metabolic syndrome positively correlated with waist circumference, glycaemia and oxidative stress markers, e. g. glutathione peroxidase and urinary isoprostane (77). Interestingly, the micro-vesicle phenotype might vary within the type of diabetes. In patients with diabetes type I, increased levels of annexin A5– and CD41-positive microvesicles have been reported, whereas in type II diabetes only annexin A5-positive microvesicles were significantly increased (79). […]
Vajen et al. teach detection of both annexin A5 and CD41 as markers for types of diabetes. Accordingly, a person having ordinary skill in the art would have at least been motivated to apply the general methods of Belle et al. using known markers for diabetes including those disclosed by Vajen et al.
Claim(s) 23 and 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent PGPub No. 2014/0011219 A1 by Belle et al. in view of Mohy Eldin et al. Journal of Applied Polymer Science 2012, 125, 1724-1735 and in further view of Vajen et al. Thromb. Haemost. 2015, 114, 228-235, as applied to claim 22 above, and in further view of Sabatier et al. Diabetes 2002, 51, 2840-2845.
Regarding instant claims 23 and 24 that embrace kits comprising the support as well as means for detecting CD41 (claim 23) and further comprising means for detecting annexin-A5, Sabatier et al. (reference (79) of Vajen et al.) teach the following on page 2841:
Reagents. Fluorescein isothyocyanate (FITC)-conjugated monoclonal antibody (mAb) against αvβ3 (FITC-CD51, clone AMF7) and phycoerythrine (PE)-conjugated mAb against platelet glycoprotein GPIIbIIIa (PE-CD41, clone P2) were used to identify endothelial microparticle (EMP) and platelet microparticle (PMP), respectively. […]
A person having ordinary skill in the art would at least been motivated to apply analogous methods of detection including the conjugated antibodies of Sabatier et al. and would have been motivated to package them together for ease of performing the detections. The same rationale applies to instant claim 24 that further embraces means for detecting annexin-A5 (or annexin V) where Sabatier et al. teach on page 2841: “For total annexin V–positive blood cell microparticle (TMP) quantitation, 30 l of plasma was incubated with FITC-annexin V.” Instant claims 23 and 24 have been interpreted to invoke 35 USC 112(f) but where the specification states on page 13 that ‘”Means for detecting or quantifying” means any means known by a person skilled in the art for detecting or quantifying a marker.’ Since the prior art demonstrates known methods of detecting the claimed markers, the prior art renders the instant claims obvious as either meeting the structure further recited on page 13 (or elsewhere in the specification) or as an equivalent thereof.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 13-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 9,453,837 in view of U.S. Patent PGPub No. 2014/0011219 A1 by Belle et al. and in further view of Mohy Eldin et al. Journal of Applied Polymer Science 2012, 125, 1724-1735 and in further view of Vajen et al. Thromb. Haemost. 2015, 114, 228-235 and in further view of Sabatier et al. Diabetes 2002, 51, 2840-2845. The claims of the patent are generic to the materials found to be obvious 35 USC 103. Since the instantly claimed subject matter was either an obvious embodiment of the claims of the patent or an obvious utility thereof, the instant claims are deemed to be obvious embodiments of the claims of the patent for the same reasons as discussed on prior art grounds, which discussions are incorporated here by reference.
Claims 13-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10,180,427 in view of U.S. Patent PGPub No. 2014/0011219 A1 by Belle et al. and in further view of Mohy Eldin et al. Journal of Applied Polymer Science 2012, 125, 1724-1735 and in further view of Vajen et al. Thromb. Haemost. 2015, 114, 228-235 and in further view of Sabatier et al. Diabetes 2002, 51, 2840-2845. The claims of the patent are generic to the methods discussed under 35 USC 103. The instant claims are deemed to be obvious embodiments of the claims of the patent for the same reasons as discussed under 35 USC 103, which discussions are incorporated here by reference. Claim 9 of the patent recites immobilization on a solid support and claim 1 of the patent recites detection of microparticles using formulae that embrace structures discussed under 35 USC 103.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATTHEW P COUGHLIN whose telephone number is (571)270-1311. The examiner can normally be reached Monday - Friday, 10 am - 6 pm EST.
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/MATTHEW P COUGHLIN/Primary Examiner, Art Unit 1626