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 .
Status of the Claims
Claims 1-13 are pending and examined herein.
Priority
The present application, filed 09/25/2023, is acknowledged and the claims examined herein are treated as having an effective filing date of 09/25/2023.
Maintained Claim Objections
The claim objections are maintained but updated to reflect the language of the amended claims presently of record. Certain previously identified informalities have been corrected; however, additional or remaining grammatical, punctuation, and claim-syntax defects require correction as set forth below.
Claim 1 is objected to because of the following informalities: the phrase “a venom of different species simultaneously” is grammatically inconsistent with the recitation of detection involving different species. The phrase should be amended to recite “venoms of different species simultaneously” or “venom from different species simultaneously,” as appropriate to Applicant’s intended scope. Claim 1 is further objected to because the comma in the phrase “a polyvalent antibody, specific to a species” improperly separates the adjective phrase from the noun it modifies. The phrase should be amended to recite “a polyvalent antibody specific to a species.” Appropriate correction is required.
Claim 6 is objected to because of the following informalities: the phrase “a venom of different snake species simultaneously” is grammatically inconsistent with the stated detection involving different snake species. The phrase should be amended to recite “venoms of different snake species simultaneously” or “venom from different snake species simultaneously,” as appropriate to Applicant’s intended scope. Claim 6 is additionally objected to because the phrase “adding species specific venom” lacks an article. Appropriate correction is required.
Claim 8 is objected to because of the following informalities: the plural subject “different snake species” requires the plural verb “comprise,” rather than “comprises.” Accordingly, “the different snake species comprises” should be amended to recite “the different snake species comprise.” Appropriate correction is required.
Claim 10 is objected to because of the following informalities: the phrase “incubating at a room temperature” is grammatically improper. The phrase should be amended to recite “incubating at room temperature.” Appropriate correction is required.
Maintained 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.
Applicant’s amendments filed 05/13/2026 have been fully considered. While the amendments overcome certain issues identified in the prior Office action, the amended claims continue to fail to particularly point out and distinctly claim the subject matter regarded as the invention. Accordingly, the rejection under 35 U.S.C. 112(b) is maintained on updated grounds as set forth below.
Claims 1-13 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 1 recites a method of detecting “a venom of different species simultaneously.” Claim 1 further recites modifying an electrode with chemical linkers “in order to facilitate immobilization of antibodies,” but subsequently recites “conjugating a polyvalent antibody, specific to a species to the modified electrode” to form “a species specific” immunosensor. Claim 1 then recites detecting “a species specific venom” by adding “the species specific venom” to “the species specific” immunosensor. It is unclear how the singular species-specific components recited in the body of the claim accomplish the simultaneous detection of venom from different species recited in the preamble. In particular, it is unclear whether claim 1 requires: a single polyvalent antibody capable of recognizing venoms from multiple different species; a plurality of species-specific antibodies immobilized on a single electrode; a plurality of polyvalent antibodies, each specific to a different species; a plurality of species-specific immunosensors; or only a single antibody, immunosensor, and venom notwithstanding the recitation of simultaneous detection of different species. The recitation of “antibodies” in the plural does not resolve the ambiguity because the operative conjugating step recites only “a polyvalent antibody” that is “specific to a species.” Likewise, the subsequent detection step recites only “a species specific venom” and “the species specific immunosensor,” without identifying multiple venoms, multiple species, or multiple immunosensors. Accordingly, the claim does not define with reasonable certainty the number, identity, or arrangement of the antibodies, venoms, species, or immunosensors required to perform the claimed simultaneous detection. For purposes of compact prosecution, claim 1 will be interpreted as requiring one or more antibody recognition reagents, including at least one polyvalent antibody, immobilized or conjugated to a GPH-GNP/cysteamine/PDITC/SPCE electrode and configured to permit detection of venoms associated with more than one species in the same assay or detection operation. Appropriate correction is required.
Claims 2-5 are rejected under 35 U.S.C. 112(b) as being indefinite because they depend from claim 1, which is indefinite. Accordingly, claims 2-5 incorporate the limitations of claim 1 and therefore inherit the indefiniteness of claim 1. Appropriate correction is required.
Claim 3 is further indefinite. Specifically, claim 3 depends from claim 1 and recites “the different species specific venom.” However, claim 1 introduces only “a species specific venom” and “the species specific venom” and does not previously introduce “different species specific venom” or a plurality of species-specific venoms. Accordingly, the phrase “the different species specific venom” lacks clear antecedent basis. Moreover, claim 3 recites the singular noun “venom” together with the plural verb “are” and states that the venom is from “different scorpion species comprising Leiurus quinquestriatus and Androctonus crassicauda.” It is therefore unclear whether claim 3 requires a single species-specific venom selected from either Leiurus quinquestriatus or Androctonus crassicauda, venoms from both species, simultaneous detection of venoms from both species, or separate species-specific detection operations directed to the respective species. Accordingly, the number and identity of the species-specific venoms required by claim 3 cannot be determined with reasonable certainty. For purposes of compact prosecution, claim 3 is interpreted as requiring detection of venoms associated with Leiurus quinquestriatus and Androctonus crassicauda in the same assay or detection operation, consistent with the interpretation applied to claim 1. Appropriate correction is required.
Claim 6 recites a method of detecting “a venom of different snake species simultaneously.” Claim 6 further recites modifying an electrode with chemical linkers “in order to facilitate immobilization of antibodies,” but subsequently recites “conjugating a polyvalent antibody specific to snake species to the modified electrode” to form “a species specific” immunosensor. Claim 6 then recites detecting “a snake specific venom” by adding “species specific venom” to “the species specific” immunosensor. It is unclear how the singular antibody, immunosensor, and venom recitations correspond to the simultaneous detection of venom from different snake species. In particular, it is unclear whether the claim requires: one polyvalent antibody capable of recognizing venoms from multiple snake species; multiple snake-species-specific antibodies; multiple polyvalent antibodies; multiple species-specific immunosensors; or only one antibody, immunosensor, and venom notwithstanding the recitation of simultaneous detection. The term “polyvalent” does not, by itself, identify the species recognized by the antibody, the number of venom antigens recognized, or the configuration by which venoms from different snake species are distinguished or detected simultaneously. Likewise, “specific to snake species” does not identify whether the antibody is specific to one snake species, several snake species, or snake venom generally. Accordingly, the claim does not define with reasonable certainty the number, identity, or arrangement of the antibodies, venoms, snake species, or immunosensors required for the claimed simultaneous detection. For purposes of compact prosecution, claim 6 will be interpreted as requiring one or more antibody recognition reagents, including at least one polyvalent antibody directed to snake venom, immobilized or conjugated to a GPH-GNP/cysteamine/PDITC/SPCE electrode and configured to permit detection of venoms associated with more than one snake species in the same assay or detection operation. Appropriate correction is required.
Claims 7-9 are rejected under 35 U.S.C. 112(b) as being indefinite because they depend from claim 6, which is indefinite. Accordingly, claims 7-9 incorporate the limitations of claim 6 and therefore inherit the indefiniteness of claim 6. Appropriate correction is required.
Claim 10 recites modifying an electrode with at least two chemical linkers “in order to facilitate the immobilization of an antibody through covalent binding” in lines 3-5. There is insufficient antecedent basis for this limitation in the claim. In particular, no immobilization or antibody has been previously introduced in the claim to provide antecedent basis for “the immobilization.” The later recitation of “conjugating a polyvalent antibody specific to scorpion species to the modified electrode” does not cure the antecedent-basis issue because the claim does not expressly establish that the subsequently conjugated polyvalent antibody is the same antibody involved in “the immobilization,” or that “conjugating” and “immobilization” refer to the same claimed operation. Accordingly, it is unclear whether “the immobilization of an antibody” refers to: the subsequent conjugation of the polyvalent antibody; a separate immobilization step not expressly recited; immobilization of a different antibody; or a general intended function of the chemical linkers rather than a required method step. The scope of claim 10 therefore cannot be determined with reasonable certainty. For purposes of compact prosecution, claim 10 will be interpreted as requiring that the at least two chemical linkers facilitate covalent immobilization of the subsequently recited polyvalent antibody on the modified GPH-GNP/SPCE electrode, and that the subsequent “conjugating” step performs that immobilization. Appropriate correction is required.
Claims 11-13 are rejected under 35 U.S.C. 112(b) as being indefinite because they depend from claim 10, which is indefinite. Accordingly, claims 11-13 incorporate the limitations of claim 10 and therefore inherits the indefiniteness of claim 10. Appropriate correction is required.
Claim 12 is further indefinite because it recites “the different scorpion species” in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. In particular, claim 10 introduces only “a scorpion species.” Claim 10 does not previously introduce a plurality of scorpion species, does not recite “different scorpion species,” and does not require simultaneous detection of venoms from more than one scorpion species. Accordingly, “the different scorpion species” lacks clear antecedent basis. It is unclear whether claim 12 requires: a single scorpion species selected from Leiurus quinquestriatus and Androctonus crassicauda; both Leiurus quinquestriatus and Androctonus crassicauda; simultaneous detection of venoms from both species; or separate detection of venom from either listed species. The use of “comprise of” does not clarify whether the listed species are alternatives or collectively required. Accordingly, the scope of claim 12 cannot be determined with reasonable certainty. For purposes of compact prosecution, claim 12 will be interpreted as requiring that the singular scorpion species recited in claim 10 is selected from Leiurus quinquestriatus and Androctonus crassicauda. Under this interpretation, claim 12 does not require simultaneous detection of venoms from both species.
Maintained 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.
The rejections under 35 U.S.C. 103 are maintained and updated in view of Applicant’s amendments. The amendments added polyvalent-antibody limitations and revised the species-specific venom-recognition configurations of the independent claims. Accordingly, the grounds of rejections have been revised to address the amended claims as a whole, including the newly added limitations.
Claims 1, 2, and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Mars et al. (Ultrasensitive sensing of Androctonus australis hector scorpion venom toxins in biological fluids using an electrochemical graphene quantum dots/nanobody-based platform. Vol. 190, December 2018) in view of Wang et al. (Electrochemical Immunosensor with Graphene/Gold Nanoparticles Platform and Ferrocene Derivatives Label. Talanta. Vol. 103, January 2013), Elshafey et al. (Electrochemical Impedance Immunosensor Based on Gold Nanoparticles–Protein G for the Detection of Cancer Marker Epidermal Growth Factor Receptor in Human Plasma and Brain Tissue. Biosensors & Bioelectronics. Vol. 50, December 2013), Raja et al. (In Situ Grown Bimetallic MOF‐Based Composite as Highly Efficient Bifunctional Electrocatalyst for Overall Water Splitting with Ultrastability at High Current Densities. Advanced Energy Materials. Vol. 8, No. 23, August 2018), Faria et al. (Development of an Impedimetric Immunosensor for Specific Detection of Snake Venom. BioNanoScience. Vol. 8, No. 4, December 2018), Vaiyapuri et al. (WO 2021/033196 A1), and Masihipour et al. (Cross-Reactivity and Neutralization Capacity of Polyspecific Antivenom Produced by Razi Institute against Three Species of Buthidea Family Scorpions. Asia Pacific Journal of Medical Toxicology. Vol. 8, No. 3, September 2019).
Regarding claims 1, 2, and 5, Mars teaches an electrochemical method for detecting scorpion venom using an antibody-functionalized graphene-based screen-printed carbon electrode. Mars expressly reports a novel electrochemical immuno-sandwich to detect the Aah50 toxic fraction within the Aah scorpion venom, using the bispecific nanobody format specially designed to highly recognize and neutralize the two most toxic molecules in the AahG50 venom fraction, and graphene quantum dots (GQDs) constructed on the surface carbon screen-printed electrodes (Abstract, p. 182). Mars teaches a screen-printed carbon electrode consisted of a 4-mm diameter working electrode, a carbon counter electrode and an Ag pseudo-reference electrode (Materials and methods, p. 183). Mars further teaches modifying the SPCE with graphene material and covalently immobilizing a venom-specific antibody. Furthermore, Mars teaches detecting species-specific venom by applying the venom to the antibody-functionalized immunosensor and incubating at room temperature. Mars states that AahG50 aliquots at different concentrations were casted on the SPCE/GQDs/anti-AahG50 and incubated for 60 min at RT (Materials and methods, p. 184). Mars also teaches monitoring a reduction-current response after venom binding. Mars explains that the analytical readout was achieved by sampling the current coming from the reduction of BQ, after formation of the immunosandwich at the surface of SPCE (Introduction, p. 183). Mars further reports that the chronoamperograms of the AahG50-GQDs immunosandwich revealed a proportional increment in the reduction current with the increase of AahG50 concentration (Results and discussion, p. 185). Importantly, Mars teaches that the device and method may be expended to develop new platforms for the other venom fractions from different animal species (Conclusions, p. 186).
However, Mars does not teach or specify a graphene-gold nanoparticle composite SPCE, cysteamine and PDITC as the two chemical linkers, washing with a DMF/water mixture and then ethanol, square-wave voltammetry, use of a polyvalent antibody as an assay recognition reagent, or configuration of the electrochemical assay to detect venoms associated with different species in the same assay or detection operation.
Wang teaches the claimed graphene-gold nanoparticle electrode architecture. Wang expressly discloses graphene (Gr)/gold nanoparticles (GNP) composite as the immobilization platform (Abstract, p. 75). Wang explains that graphene has large accessible surface area, provides an abundant domain for bimolecular binding, and provides fast electron-transfer kinetics and further signal amplification in electrochemical detection (Introduction, p. 75). Wang additionally states that gold nanoparticles have been extensively employed as immobilization platform and that the combination of Gr with GNP as a platform will be fascinating and desirable (Introduction, p. 75). Wang further prepares the composite by forming graphene on an electrode and subsequently depositing gold nanoparticles (Experimental, p. 76). Wang further teaches that the Ab1 molecules were adsorbed on the surface of the GNP/Gr by the covalent bonding of Au of GNP and NH2 of the protein (Results and discussion, p. 77; Fig. 1), and that GNP/Gr film acts as high electron relay for shuttling electron between the electrochemical probe and the electrode (Results and discussion, p. 77; Fig. 2
Elshafey teaches modifying a gold-nanoparticle electrode using cysteamine and PDITC to provide linker-mediated antibody immobilization. Elshafey expressly teaches square-wave voltammetry and monitoring peak-current changes during immunosensor fabrication and antigen binding. In particular, Elshafey states that the proposed immunosensor is characterized by employing cyclic voltammetry (CV), square wave voltammetry (SWV) and EIS in the presence of [Fe(CN)6]3−/[Fe(CN)6]4− redox probe (Introduction, p. 144), that CV and SWV have been employed to monitor the fabrication process of the immunosensor (Results and discussion, p. 145), that SWV is more sensitive than CV, and that the peak currents differences were clearly observed for the electrode modification steps (Results and discussion, p. 145; Fig. 2B). Elshafey further reports that a further decrease of the peak current and an increase of the peak separation were also observed, after the immunochemical binding of the EGFR antigens, and that the same behavior was observed using SWV (Results and discussion, p. 145; Fig. 2B).
Raja teaches the use of DMF, water, and ethanol as sequential processing solvents in fabricating an electrochemically active electrode-supported material. Raja discloses that the electrode-supported composite was synthesized in DMF and that the resulting material was washed with DMF, water, and ethanol sequentially and dried for later use (Experimental section, p. 9).
Faria teaches an electrochemical venom immunosensor using antibodies produced from a venom pool representing multiple snake species. Faria teaches the detection of venoms from Bothrops snakes using electrochemical impedance spectroscopy techniques. Faria discloses a transducer substrate functionalized with antibothropic antibodies (Abstract, p. 988). Faria further teaches that the antibodies were obtained from plasma of horses hyperimmunized with a venom pool of snakes of B. jararacussu, B. jararaca, B. neuwiedi, B. moojeni, and B. alternatus (Experimental, p. 989). Thus, Faria establishes that an antibody preparation generated using venoms from multiple species remains functional when immobilized on an electrochemical transducer. Faria further states that the immunosensor was incubated with different concentrations of venoms from Bothrops, Crotalus, and Micrurus in order to evaluate its specificity, and that formation of the antigen-antibody immunocomplex at the surface of the transducer substrate produced a concentration-dependent electrochemical response when the device was exposed to the bothropic venom (Abstract, p. 988). Faria additionally teaches that to evaluate its specificity, the immunosensor was incubated with solutions of other snake venoms, Crotalus durissus terrificus and Micrurus leminiscatus, at the same concentration of Bothrops (Experimental, p. 990).
Vaiyapuri teaches polyvalent antibodies for use to detect a specific species or a collection of species of venoms (taxon) ([0008] and [0069]). Vaiyapuri states that the assay device may be a multi-well assay device that support simultaneous detection of samples from the same or different subjects. Vaiyapuri further states that the detection and capture antibodies are highly specific and have little to no cross-reactivity, detecting only single species or even only specific sub-species, while in others the extent of cross-reactivity is such that entire families or even orders may be detected with the kit ([0069], p. 16). Vaiyapuri further discloses that in addition to snakebite envenomation and snake venoms, the inventionmay be used for detecting other venoms from diverse range of species, including reptile venoms, as well as lizard; invertebrate venoms; fish venoms and mammal venoms amongst others ([0085], p. 20).
Masihipour independently teaches a polyvalent scorpion-antibody preparation having functional recognition across multiple scorpion species. Specifically, Masihipour discloses polyvalent antivenom against six species of scorpions(Abstract, p. 90). Masihipour teaches that anti-serum polyvalent is obtained from the hyperimmune serum of the horse, and that antisera has the ability to neutralize the venom of different species of scorpion based on the structural similarities of different species of venom (Introduction, p. 90). Masihipour further states that polyvalent anti-serum is produced from the venom of six scorpion species (Introduction, p. 90). Masihipour expressly identifies the reagent as an antibody, stating that the cross-reactivity of polyvalent antibody produced by Razi Vaccine and Serum Research Institute was tested against these three scorpions which are not included in antivenom production (Discussion, p. 94). Masihipour further reports that this polyvalent antivenom is capable of neutralizing all three scorpion species Apistobuthus susanae, Buthacus macrocentrus, and Vachoniolus iranus (Discussion, p. 94). Masihipour also explains that polyvalent scorpion antivenom is produced against a few species but according to cross-reaction ability to neutralize multiple scorpion venoms, and that the antisera had the ability to neutralize the range of scorpion species found in Iran (Discussion, p. 92).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the antibody-functionalized GQD/SPCE venom immunosensor of Mars by employing the graphene-gold nanoparticle immobilization platform of Wang to increase accessible electrode surface area, antibody loading, electron-transfer kinetics, and electrochemical response; by applying the cysteamine/PDITC linker architecture, DMF-containing activation procedure, water and DMF washing, room-temperature antigen incubation, and SWV peak-current monitoring of Elshafey to provide stable linker-mediated antibody attachment and a sensitive known electrochemical readout; and by adapting the known DMF, water, and ethanol electrode-processing sequence of Raja so that DMF and water are used as a mixed wash followed by ethanol, which would have been a routine and predictable variation of the same known solvent set in the absence of any claimed critical mixing ratio or unexpected result. It further would have been obvious to implement Mars’s express recommendation to expand its sensing principle to venom fractions from different animal species by employing Faria’s established electrochemical use of an antibody preparation generated from a multispecies venom pool, thereby confirming that multispecies-derived venom-recognition antibodies were compatible with electrochemical venom sensing, and by configuring the resulting platform according to Vaiyapuri’s common multispecies assay arrangement so that venom-recognition reactions associated with different species are carried out within the same assay or detection operation. Vaiyapuri expressly teaches that the assay capture or detector antibody may be a polyvalent antivenom, while Masihipour independently teaches a polyvalent antibody capable of functionally recognizing venoms from multiple scorpion species. Thus, selecting a known polyvalent venom-recognition antibody for the modified Mars platform would not have required creating a new antibody function; it would merely have substituted a known multispecies-reactive recognition reagent for Mars’s single-species recognition reagent, with the polyvalent antibody continuing to perform its established function of binding venom antigens shared among or associated with different species. Likewise, arranging the known species-directed recognition reactions for operation together would have been the predictable application of Vaiyapuri’s known multispecies assay organization to Mars’s electrochemical detection platform, while retaining Mars’s established electrochemical transduction mechanism.
The prior art therefore supplies an express teaching, suggestion, and motivation to make the combination: Mars expressly directs expansion to different animal species, Faria demonstrates electrochemical compatibility of multispecies-derived venom antibodies, Vaiyapuri teaches simultaneous multispecies venom-assay organization within a common venom-detection assay and polyvalent antivenom capture or detector antibodies, and Masihipour confirms functional multispecies recognition by a polyvalent scorpion antibody. The modifications additionally represent the combination of known elements according to their established functions and the use of known assay and electrode-improvement techniques in the same manner to obtain predictable results. A person of ordinary skill would have had a reasonable expectation of success because Mars already demonstrates covalent venom-antibody immobilization, room-temperature venom binding, and reduction-current transduction on a graphene-modified SPCE; Wang demonstrates successful antibody immobilization and enhanced electron transfer on a graphene-gold nanoparticle platform; Elshafey demonstrates successful cysteamine/PDITC-mediated attachment and SWV detection of antigen-induced peak-current variation; Raja demonstrates compatibility of DMF, water, and ethanol with electrode processing; Faria demonstrates that a multispecies-derived venom-antibody preparation retains recognition activity on an electrochemical transducer; Vaiyapuri demonstrates the operative use of polyvalent antivenom antibodies and multiple species-directed recognition reactions within a common venom-detection assay; and Masihipour demonstrates that a polyvalent scorpion antibody recognizes venoms associated with multiple species. Each component would therefore perform the same established function it performs in the prior art, and no cited reference identifies any technical incompatibility between the electrode architecture, linker chemistry, polyvalent antibody reagent, multispecies assay organization, and electrochemical readout.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Mars et al., Wang et al., Elshafey et al., Raja et al., Faria et al., Vaiyapuri et al., and Masihipour et al., as applied to claim 1 above, and further in view of Ozkan et al. (Evaluation of the Neutralizing Capacity of Androctonus Crassicauda (Olivier, 1807) Antivenom against Leiurus Quinquestriatus (Ehrenberg, 1928) Venom (Scorpiones: Buthidae). The Journal of Venomous Animals and Toxins Including Tropical Diseases. Vol. 14, No. 3, August 2008).
With respect to the teachings Mars et al., Wang et al., Elshafey et al., Raja et al., Faria et al., Vaiyapuri et al., and Masihipour et al., see the discussion above, which applies equally here. These references differ from the instant claim in failing to teach or specify the scorpion species recited in claim 3, namely: Leiurus quinquestriatus and Androctonus crassicauda.
Ozkan discloses the evaluation of the neutralizing capacity of Androctonus crassicauda antivenom against Leiurus quinquestriatus. Sera produced by Refik Saydam Hygiene Center (RSHC) showed strong reactivity against the venoms of A. crassicauda and L. quinquestriatus in western blotting and dot-blot analysis and that RSHC anti-Ac presents immunoactivity and neutralizing potential against Leiurus quinquestriatus venom (Abstract, p. 481). Ozkan reports that the antivenom reacted strongly with A. crassicauda venom and that western blotting also showed the presence of L. quinquestriatus venom components recognized by RSHC anti-Ac (Results, p. 486). Ozkan further states that Figure 2 shows the strong reaction of L. quinquestriatus venom protein with RSHC anti-Ac (Results, p. 486). Consistent with these disclosures, Figure 1 shows venom components from both L. quinquestriatus and A. crassicauda detected using RSHC anti-Ac (Fig. 1, p. 487), and Figure 2 shows strong immunoreactivity between the antivenom and venom proteins from both species (Fig. 2, p. 488).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the multispecies venom-detecting electrochemical immunosensor of claim 1 to detect venoms from Leiurus quinquestriatus and Androctonus crassicauda, as taught by Ozkan. Ozkan expressly identifies those species as highly poisonous and medically significant and demonstrates that an antibody preparation directed against A. crassicauda recognizes venom components from both A. crassicauda and L. quinquestriatus. A person of ordinary skill implementing Mars’s express recommendation therefore would have been motivated to select the medically significant L. quinquestriatus and A. crassicauda venom targets identified by Ozkan and to use a multispecies-reactive scorpion antibody in the modified electrochemical immunosensor, thereby permitting detection of venoms associated with the two recited species in the same assay or detection operation. The modification follows an express teaching, suggestion, and motivation in the prior art and constitutes the predictable application of known antigen-antibody recognition to known scorpion-venom targets, while retaining the electrochemical transduction mechanism already established by the claim 1 combination.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Mars et al., Wang et al., Elshafey et al., Raja et al., Faria et al., Vaiyapuri et al., and Masihipour et al., as applied to claim 1 above, and further in view of Haidar et al. (Snake Bites in the Arabian Peninsula, a Review Article. Journal of Arid Environments. Vol. 112, January 2015).
With respect to the teachings Mars et al., Wang et al., Elshafey et al., Raja et al., Faria et al., Vaiyapuri et al., and Masihipour et al., see the discussion above, which applies equally here. These references differ from the instant claim in failing to teach or specify the snake species recited in claim 4, namely: Naja arabica, Walterinnesia aegyptia, Bitis arietans, Cerastes cerastes, Echis coloratus, and Echis carinatus.
Haidar teaches medically significant venomous snake species of the Arabian Peninsula, including each species recited in claim 4. Haidar further identifies the most common venomous snakes for this region as including Echis carinatus and E. coloratus (Results and discussion, p. 160). Table 1 expressly identifies Cerastes cerastes, Echis carinatus sochureki, Echis coloratus, Bitis arietans, Walterinnesia aegyptia, and Naja arabica as venomous snakes present in the Arabian Peninsula (Table 1, p. 161). Haidar additionally teaches the known use of a polyvalent antivenom directed against toxins from multiple medically important snake species. Haidar states that antivenom is a polyvalent compound and that the antivenom was prepared against the toxin from Bitis arietans, Cerastes cerastes, E. coloratus, E. carinatus, Naja haje, and Walterinnesia aegyptia but can cover other species because of the phylogenetic aspects of toxin production (Results and discussion, p. 162). Also, Haidar explains that difficulties in identifying the snake type by the emergency physician indicate the need for an identification kit (ELISA) and indicates these kits are usually unavailable and their use still requires testing to rule out false positive and false negative for the local snakes in order to use monovalent antivenom. This makes the use of a monovalent less suitable in all hospitals as compared to the polyvalent, providing the polyvalent is manufactured based on the local snake species (Results and discussion, p. 162).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the multispecies venom-detecting electrochemical immunosensor of claim 1 to detect venoms associated with Naja arabica, Walterinnesia aegyptia, Bitis arietans, Cerastes cerastes, Echis coloratus, and Echis carinatus, as taught by Haidar. Haidar expressly identifies each of those species as a medically significant venomous snake of the Arabian Peninsula and teaches a polyvalent antivenom prepared against toxins from Walterinnesia aegyptia, Bitis arietans, Cerastes cerastes, Echis coloratus, and Echis carinatus, with coverage extendable to other related species because of phylogenetic relationships among venom toxins. A skilled artisan implementing Mars’s express recommendation therefore would have been motivated to select the six snake-venom targets identified by Haidar and to configure the modified Mars platform with appropriate species-reactive or polyvalent snake-venom antibodies so that venoms associated with those species could be detected within the same assay or detection operation. This modification follows an express teaching, suggestion, and motivation in the prior art and represents the predictable application of known multispecies venom-recognition reagents and assay organization to known medically significant snake-venom analytes.
Claims 6, 7, 8, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Mars et al. in view of Wang et al., Elshafey et al., Raja et al., Faria et al., Vaiyapuri et al., and Haidar et al.
Regarding claims 6, 7, and 9, with respect to the teachings Mars et al., Wang et al., Elshafey et al., Raja et al., Faria et al., Vaiyapuri et al., and Haidar et al., see the discussion above, which applies equally here.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the antibody-functionalized GQD/SPCE venom immunosensor of Mars by employing the graphene-gold nanoparticle immobilization platform of Wang to increase accessible electrode surface area, antibody loading, electron-transfer kinetics, and electrochemical response; by applying the cysteamine/PDITC linker architecture, DMF-containing activation procedure, water and DMF washing, room-temperature antigen incubation, and SWV peak-current monitoring of Elshafey to provide stable linker-mediated antibody attachment and a sensitive established electrochemical readout; and by adapting the known DMF, water, and ethanol electrode-processing sequence of Raja so that DMF and water are used as a mixed wash followed by ethanol, which would have been a routine and predictable variation of the same known solvent set in the absence of any claimed critical mixing ratio or unexpected result. It further would have been obvious to implement Mars’s express recommendation to expand its sensing principle to venom fractions from different animal species by applying Faria’s electrochemical implementation of antibodies generated from a multispecies snake-venom pool, thereby establishing that multispecies-derived snake-venom antibodies were compatible with electrochemical transduction, and by configuring the resulting Mars platform according to Vaiyapuri’s common multispecies snake-venom assay arrangement so that recognition reactions associated with different snake species are performed within the same assay or detection operation. Vaiyapuri expressly teaches that the assay capture or detector antibody may be a polyvalent antivenom, while Haidar independently teaches a polyvalent snake-antivenom preparation directed against toxins from multiple snake species and expressly identifies the clinical advantage of polyvalent recognition when the offending snake cannot readily be identified. Thus, selecting a known polyvalent snake-venom antibody for the modified Mars platform would have been a predictable substitution of a known multispecies-reactive recognition reagent for Mars’s more narrowly directed venom-recognition reagent, with the polyvalent antibody continuing to perform its established function of binding venom antigens associated with multiple snake species. Likewise, organizing the species-directed recognition reactions for operation together would have been the predictable application of Vaiyapuri’s known simultaneous multispecies assay arrangement to Mars’s electrochemical platform while retaining Mars’s established electrochemical transduction mechanism.
Regarding claim 8, refer to the teachings of Haidar above, which applies equally here. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to configure the multispecies snake-venom immunosensor of claim 6 to detect venoms associated with Naja arabica, Walterinnesia aegyptia, Bitis arietans, Cerastes cerastes, Echis coloratus, and Echis carinatus because Haidar expressly identifies each of these species as a medically important venomous snake and teaches a polyvalent antivenom prepared against toxins from the same with recognition extending to other related species based on phylogenetic relationships among venom toxins. A skilled artisan implementing Mars’s express recommendation therefore would have been motivated to select the six clinically significant snake-venom targets identified by Haidar and to employ appropriate species-reactive or polyvalent snake-venom antibodies in the modified electrochemical platform so that venoms associated with those species could be detected within the same assay or detection operation. This modification follows an express teaching, suggestion, and motivation in the prior art and represents the predictable application of known multispecies venom-recognition reagents and assay organization to known medically significant snake-venom analytes.
Claims 10, 11, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Mars et al. in view of Wang et al., Elshafey et al., Raja et al., and Masihipour et al.
Regarding claims 10, 11, and 13, with respect to the teachings Mars et al., Wang et al., Elshafey et al., Raja et al., and Masihipour et al., see the discussion above, which applies equally here.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the antibody-functionalized GQD/SPCE scorpion-venom immunosensor of Mars by employing the graphene-gold nanoparticle immobilization platform of Wang to increase accessible electrode surface area, antibody loading, electron-transfer kinetics, and electrochemical response; by applying the cysteamine/PDITC linker architecture, DMF-containing activation procedure, water and DMF washing, room-temperature antigen incubation, and SWV peak-current monitoring of Elshafey to provide stable linker-mediated antibody attachment and a sensitive established electrochemical readout; by adapting the known DMF, water, and ethanol electrode-processing sequence of Raja so that DMF and water are used as a mixed wash followed by ethanol, which would have been a routine and predictable variation of the same known solvent set in the absence of any claimed critical mixing ratio or unexpected result; and by selecting Masihipour’s known polyvalent scorpion antibody as the venom-recognition reagent conjugated to the modified electrode. Mars itself supplies the express teaching, suggestion, and motivation to make that latter modification because Mars directs the skilled artisan to expand the same sensing principle to other venom fractions from different animal species, while Masihipour supplies the specific known reagent capable of recognizing venoms associated with multiple scorpion species. Replacing Mars’s narrowly directed anti-AahG50 recognition reagent with a known polyvalent scorpion-antibody preparation would therefore have been a predictable substitution of one known scorpion-venom recognition reagent for another, with the polyvalent antibody performing the same established antigen-binding function while broadening the scorpion-venom targets that could be recognized. The prior art thus provides both an express reason to broaden Mars’s platform and a known scorpion-specific polyvalent reagent for accomplishing that objective.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Mars et al., Wang et al., Elshafey et al., Raja et al., and Masihipour et al., as applied to claim 10 above, and further in view of Ozkan et al.
With respect to the teachings Mars et al., Wang et al., Elshafey et al., Raja et al., and Masihipour et al., see the discussion above, which applies equally here. These references differ from the instant claim in failing to teach or specify the scorpion species recited in claim 12, namely: Leiurus quinquestriatus and Androctonus crassicauda.
As discussed above, Ozkan expressly teaches both recited scorpion species and their immunological relationship. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the electrochemical scorpion-venom immunosensor of claim 10 by selecting Leiurus quinquestriatus or Androctonus crassicauda as the scorpion-venom target, as taught by Ozkan, because Ozkan expressly identifies those species as medically important and highly venomous scorpions and demonstrates successful antibody recognition of venom proteins from each species. A person of ordinary skill in the art would have been motivated to implement Mars’s express expansion teaching by configuring the modified electrochemical platform to detect venom from either of the specifically identified scorpion species using the known polyvalent scorpion-antibody recognition strategy. This modification represents the application of known antigen-antibody recognition to known medically important scorpion venoms using the established electrochemical sensing platform of Mars. A person of ordinary skill in the art would have had a reasonable expectation of success because Mars already demonstrates a functional antibody-immobilized electrochemical immunosensor for scorpion venom, Masihipour demonstrates that polyvalent scorpion antibodies successfully recognize multiple scorpion venoms, and Ozkan experimentally confirms strong antibody reactivity toward venom proteins from both Leiurus quinquestriatus and Androctonus crassicauda.
Response to Arguments
Applicant's arguments filed 05/13/2026 have been fully considered but they are not persuasive. The objections and rejections are addressed below.
Claim Objections
Applicant argues that claims 1, 3, 4, 6, 8, 10, and 12 were amended to comply with all formal objections and that the claims are now in condition for allowance. This argument is not persuasive because several informalities remain in the amended claims. To the extent the prior objections concerned antecedent-basis defects that Applicant corrected by introducing or clarifying the modified electrode, species-specific venom, or related terms, those particular objections are withdrawn. However, the objections discussed above in this action are maintained or updated because the amended language continues to contain grammatical or formal defects.
Rejections Under 35 U.S.C. § 112(b)
Applicant argues that the amendments cured the previously identified indefiniteness and that amended claims 1–13 are now in condition for allowance. Although Applicant’s amendments resolve certain issues identified in the prior Office Action, the amended claims continue to contain indefiniteness under revised and updated grounds set forth above and below. Accordingly, the rejection under 35 U.S.C. 112(b) is maintained in modified form.
Amended claim 1 requires, in its preamble, detecting venom associated with different species simultaneously. The body of the claim, however, recites: conjugating a polyvalent antibody, specific to a species; forming a species specific immunosensor; adding the species specific venom; and monitoring current variation after binding of that singular species-specific venom. The amended language does not make reasonably clear whether claim 1 requires: one polyvalent antibody immobilized on one immunosensor and capable of producing a common response to venoms from multiple species; multiple antibodies, including at least one polyvalent antibody, immobilized on one or more sensing regions; multiple species-specific immunosensors operated together; separate electrodes or sensing regions producing independently resolved signals; or merely an assay having broad recognition capability without differentiating which species produced the signal. The ambiguity is material because Applicant’s remarks characterize the invention as a single multiplex platform having dual electrodes, immobilized polyvalent antibodies, differential identification of several venom sources, and simultaneous detection of six snake venoms and two scorpion venoms. Those requirements are not stated with corresponding clarity in claim 1. Instead, claim 1 simultaneously uses plural concepts—different species and antibodies—and singular concepts—a polyvalent antibody, a species, a species-specific immunosensor, and a species-specific venom.
The addition of polyvalent does not resolve the ambiguity. A polyvalent antibody preparation may recognize multiple antigens, epitopes, toxins, or related venoms, but the term alone does not establish whether the claim requires multiple species-resolved reactions, a common cross-reactive signal, separate sensing regions, or simultaneous identification of the source of each venom. The metes and bounds of the claimed simultaneous-detection arrangement therefore remain uncertain. Claim 6 contains the same ambiguity in the snake-specific context. It requires simultaneous detection of venom from different snake species but recites a singular polyvalent antibody, a singular species-specific immunosensor, and a singular snake-specific venom. Claims 2–5 depend from claim 1, and claims 7–9 depend from claim 6. Those dependent claims incorporate the unresolved ambiguity of their respective independent claims. Accordingly, the rejection of claims 1–9 under 35 U.S.C. § 112(b) is maintained and updated in view of Applicant’s amendments.
The prior rejection of claim 10 was based substantially on the inconsistency between the scorpion-venom context of the claim and the former references to a snake-species antibody and snake-specific venom. Applicant amended claim 10 to recite a polyvalent antibody specific to scorpion species and detection of a scorpion-specific venom. Accordingly, Applicant’s amendment overcomes the specific inconsistency identified in the prior Office Action. However, the amendment does not place claim 10 in condition for allowance because the claim remains indefinite under the updated grounds of rejection set forth in this Office Action. As explained in the rejection, claim 10 recites modifying an electrode with chemical linkers “in order to facilitate the immobilization of an antibody through covalent binding,” but no antecedent or explicit immobilization step establishes with reasonable certainty what “the immobilization” refers to. The subsequently recited step of conjugating a polyvalent antibody to the modified electrode does not clearly establish whether that conjugation constitutes the previously recited immobilization, whether a separate immobilization step is required, or whether a different antibody is involved. Consequently, the scope of the claimed method remains uncertain. Accordingly, the rejection of claim 10 under 35 U.S.C. 112(b) is maintained on the revised grounds set forth in this Office Action. Claims 11 and 13 depend from claim 10 and therefore incorporate the limitations of claim 10. Accordingly, the rejection of claims 11 -13 under 35 U.S.C. 112(b) is likewise maintained.
The rejection of claim 12 under 35 U.S.C. § 112(b) is further maintained on the revised grounds set forth in this Office Action. Claim 10 recites detection of venom from a scorpion species. Claim 12 then recites the different scorpion species, although claim 10 does not previously introduce different scorpion species. Moreover, claim 12 lists Leiurus quinquestriatus and Androctonus crassicauda in the conjunctive context of different scorpion species, while claim 10 is directed to a singular scorpion species and does not require simultaneous multispecies detection. It is therefore unclear whether claim 12 requires: selection of either L. quinquestriatus or A. crassicauda as the singular species of claim 10; detection of both species; simultaneous detection of both species; a polyvalent antibody reactive with both species; or separate species-specific immunosensors for the two species. Accordingly, claim 12 remains indefinite.
Rejections Under 35 U.S.C. § 103
Applicant argues that the claimed invention requires a single multiplex electrochemical platform having dual screen-printed carbon electrodes, separate species-specific sensing architecture, differential identification of the source of envenomation, simultaneous detection of six snake venoms and two scorpion venoms, and clinical selection of the appropriate antivenom. In response to applicant’s argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., a single integrated multiplex platform having dual electrodes, independently addressable sensing regions, separate species-resolved electrochemical signals, differential identification of each venom source, simultaneous identification of six snake venoms and two scorpion venoms, a label-free assay, a single-antibody recognition format, and clinical selection of an appropriate antivenom) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Claims 1 and 6 recite simultaneous detection but do not recite multiplex, dual electrodes, independently addressable sensing regions, separate signals, species-resolved signals, differential identification, or identification of the origin of envenomation. Claim 1 does not require simultaneous identification of every snake and scorpion species listed in the application. Claim 6 does not require simultaneous identification of all six snake species listed in dependent claim 8.
Applicant’s reliance on an alleged dual electrode architecture is also unsupported by the claim language. The claims repeatedly recite a GPH-GNP-SPCE electrode and the modified electrode. They do not recite two electrodes, dual electrodes, an electrode array, or separate electrode channels. Applicant’s asserted label-free and single-antibody distinctions are likewise not claim limitations. The claims do not exclude sandwich assays, detector antibodies, redox mediators, labels, or additional antibody-recognition reagents. Indeed, claim 1 initially recites immobilization of antibodies in the plural and subsequently recites a polyvalent antibody. Accordingly, those unclaimed distinctions do not establish patentability.
Applicant analyzes Mars, Wang, Elshafey, Raja, Faria, Ozkan, and Haidar individually and argues that each reference lacks one or more aspects of Applicant’s asserted complete multiplex platform. In response to applicant’s arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The rejection does not assert that Mars, Wang, Elshafey, Raja, Faria, Vaiyapuri, Masihipour, Ozkan, or Haidar individually anticipates the claims. The rejection under §103 expressly identifies the limitations supplied by each reference and explains why a person of ordinary skill would have combined or adapted those teachings. Applicant’s repeated observation that a given secondary reference does not itself disclose an electrochemical venom sensor, the complete claimed electrode, the complete wash process, the complete antibody configuration, and simultaneous multispecies detection does not address the actual combination. The relevant inquiry is what the combined teachings would have suggested to a person of ordinary skill, not whether each secondary reference independently discloses the complete invention.
Applicant argues, for example, that Wang employs a glassy carbon electrode and ferrocene labels, that Elshafey employs a gold electrode and detects EGFR, and that Faria employs a steel substrate. Applicant therefore contends that the systems are fundamentally different and cannot establish obviousness. In response to applicant’s argument that the secondary references disclose different complete devices, substrates, analytes, assay formats, labels, or end uses and therefore cannot be incorporated bodily into Mars, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). The rejection does not propose substituting the entire Wang assay, entire Elshafey assay, entire Raja water-splitting system, or entire Faria substrate into Mars. Instead, each reference is relied upon for a specific known feature: Wang for the graphene-gold nanoparticle immobilization platform and its known surface-area and electron-transfer benefits; Elshafey for cysteamine/PDITC surface functionalization, antibody attachment, room-temperature incubation, and SWV monitoring; Raja for the known use of DMF, water, and ethanol as electrode-processing solvents; Faria for the compatibility of multispecies-derived venom antibodies with an electrochemical venom immunosensor; Vaiyapuri for simultaneous multispecies venom-assay organization and use of polyvalent antivenom as a capture or detection antibody; Masihipour for a polyvalent scorpion antibody functionally reactive with multiple scorpion venoms; Ozkan for the specifically recited scorpion species and demonstrated immunological recognition of their venoms; and Haidar for the specifically recited snake species, known polyvalent snake-antivenom preparation, and identified need for multispecies snake identification. Those teachings are applied to the Mars electrochemical venom-sensing platform while retaining Mars’s fundamental antigen-antibody binding and electrochemical transduction operation.
Applicant argues that Mars is limited to a single AahG50 scorpion-venom fraction and does not disclose multiple venom types, polyvalent antibodies, or simultaneous detection. The Office agrees that Mars does not alone disclose every claim limitation. That is why the rejection is under §103 in combination with additional references. Mars nevertheless provides the operative electrochemical venom-sensing foundation: a graphene-modified SPCE, covalent immobilization of a venom-recognition antibody, room-temperature exposure to scorpion venom, formation of an immunosandwich on the SPCE, and a concentration-dependent reduction-current response. More importantly, Mars expressly states that its sensing principle can be expanded to other venom fractions from different animal species. That express statement contradicts Applicant’s characterization of Mars as technologically exclusive to one analyte and supplies a direct reason to consult additional art addressing other venom species, antibody reagents, and assay organizations. The updated rejection expressly identifies that disclosure as the bridge motivation for the combination. Mars is therefore not being relied upon as teaching the complete claimed combination. It supplies the electrochemical venom-sensing base platform and an express instruction to broaden that platform.
Applicant argues that Wang uses a glassy carbon electrode, direct adsorption, a sandwich format, ferrocene labels, and human IgG rather than venom. Those distinctions do not negate Wang’s relevant teaching. Wang is relied upon for its graphene/gold nanoparticle composite immobilization platform, antibody attachment to the GNP/graphene surface, improved electron transfer, and enhanced electrochemical response. The rejection does not require retaining Wang’s human-IgG analyte, complete sandwich architecture, or ferrocene-labelled detector configuration. The claimed method does not exclude a sandwich format or labels, and it does not require a label-free system. Further, Wang expressly presents graphene/gold nanoparticles as an antibody-immobilization platform, which is the same technical function for which the teaching is applied in the rejection.
Applicant argues that Elshafey uses a single gold electrode, detects EGFR, and lacks multiplex venom detection. Elshafey is not relied upon for the claimed venom analyte or simultaneous multispecies function. It is relied upon for the expressly disclosed AuNP/cysteamine/PDITC linker architecture, antibody immobilization, DMF-containing functionalization, water and DMF washing, room-temperature antigen incubation, SWV, and antigen-induced peak-current variation. Those surface-functionalization and electrochemical-monitoring techniques do not depend upon EGFR being the analyte. The rejection applies the known chemistry and readout technique to the analogous antibody-functionalized electrochemical venom sensor of Mars. Applicant has not identified evidence that cysteamine/PDITC attachment or SWV would cease to perform its known function when the immobilized antibody recognizes venom rather than EGFR.
Applicant argues that Raja concerns a metal-organic-framework water-splitting electrocatalyst and is in a different field from venom biosensing. In response to applicant’s argument that Raja et al., Ozkan et al., and Haidar et al. is nonanalogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, Raja is reasonably pertinent to the claimed electrode-processing problem because it expressly discloses processing an electrochemically active electrode-supported material with DMF, water, and ethanol; Ozkan is reasonably pertinent to selecting and immunologically recognizing the expressly claimed scorpion-venom analytes; and Haidar is reasonably pertinent to selecting the expressly claimed snake-venom sources and employing a polyvalent venom-recognition preparation directed to those sources.
Raja is used narrowly for its electrode-processing solvent teaching. The claimed wash limitation itself concerns treatment of a modified electrode with DMF, water, and ethanol. A reference teaching the compatibility and sequential use of those same solvents in preparing an electrochemically active electrode-supported material is reasonably pertinent to that processing question, even though Raja’s ultimate electrocatalytic application differs. The rejection instead explains why, absent any claimed ratio, concentration, time, temperature, demonstrated criticality, or unexpected result attributable to premixing, employing the two known wash media together before the known ethanol wash would have been a predictable process variation.
Applicant argues that Faria uses a steel substrate, lacks the claimed electrode architecture, and detects only Bothrops venom rather than simultaneously detecting the asserted six snake and two scorpion venoms. Faria is not relied upon for the complete electrode architecture or the simultaneous assay arrangement. Mars, Wang, and Elshafey address the electrochemical platform and surface chemistry. Vaiyapuri addresses the multispecies assay arrangement. Faria performs a distinct bridging function. It demonstrates that antibodies obtained from horses hyperimmunized with a pool of venoms from multiple snake species remain functional when incorporated into an electrochemical venom immunosensor. It also evaluates responses to venoms from multiple snake genera. Faria therefore supplies direct evidence that multispecies-derived venom antibodies are compatible with electrochemical transduction, addressing the technical connection between the antibody art and Mars’s electrochemical venom platform.
Applicant argues that Ozkan is limited to therapeutic neutralization, western blotting, and dot-blot testing and does not disclose an electrochemical sensor. Ozkan is not relied upon for the electrode or electrochemical transduction. It is relied upon for: Leiurus quinquestriatus; Androctonus crassicauda; the medical significance of those species; and experimental evidence that an antibody preparation directed against one recognizes venom proteins from both species. Those teachings are directly pertinent to claims 3 and 12. Ozkan supplies the narrowed analyte selection and immunological relationship required by the dependent claims.
Applicant argues that Haidar is a review article lacking a biosensor, electrochemical detection method, or analytical device. Haidar is not relied upon for an electrochemical device. It is relied upon for the expressly listed medically important snake species, a polyvalent antivenom directed against toxins from several of those species, recognition coverage extending to related species, and the stated need for an identification kit where the offending snake cannot readily be identified. Those teachings are directly pertinent to the species and polyvalent-antibody limitations of claims 4, 6, and 8.
Applicant argues that the cited references do not disclose simultaneous identification of multiple snake and scorpion venoms within a single multiplex platform. As an initial matter, that argument depends upon limitations not recited in the claims. Claims 1 and 6 do not require identification of all listed venoms, species-resolved output, separate signals, or a single integrated dual-electrode multiplex chip. Nevertheless, the updated combination also addresses the recited simultaneous-detection requirement directly. Mars expressly invites extension of its electrochemical sensing principle to venom fractions from different animal species. Faria demonstrates electrochemical compatibility of antibodies generated from venoms of multiple species. Vaiyapuri expressly teaches simultaneous detection of samples from different snake venoms and organizes multiple species-directed recognition reactions within a common assay or detection operation. Under the interpretation placed on the record, the combined system permits venoms associated with more than one species to be detected in the same assay or detection operation. The electrochemical mode of transduction does not require the antigen-recognition arrangement itself to have originated in an electrochemical reference, because Mars already supplies the electrochemical transduction mechanism and the rejection provides a reason to apply the known multispecies assay arrangement to that platform. For claims 3 and 4, the relevant dependent-claim species are separately addressed by Ozkan and Haidar. No independent claim requires the species lists of claims 3 and 4 to be combined and simultaneously differentiated. Claim 10, by contrast, does not recite simultaneously and is directed to detection of venom from a scorpion species. Applicant’s simultaneous-multiplex arguments therefore do not distinguish claim 10 or claims 11–13 depending therefrom.
Applicant argues that the references do not disclose a species-specific GPH-GNP/cysteamine/PDITC/SPCE electrode having immobilized polyvalent antibodies for simultaneous multispecies venom detection. The argument improperly requires a single reference to disclose the entire combination. The updated rejections assign the relevant teachings as follows: Mars supplies the antibody-functionalized electrochemical venom-sensor platform and expressly recommends extension to other species; Wang and Elshafey supply the claimed electrode and immobilization architecture; Vaiyapuri expressly teaches use of polyvalent antivenom as a capture or detection antibody in a multispecies venom assay; Masihipour supplies a known polyvalent scorpion antibody with multispecies recognition; Haidar supplies a known polyvalent snake-antivenom directed to multiple species; and Faria confirms that multispecies-derived venom antibodies function on an electrochemical transducer.
Applicant argues that the proposed combination is not supported by a teaching, suggestion, or motivation and represents an impermissible reconstruction of the invention. 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 this case, the combination is driven by express teachings in the art rather than by Applicant’s disclosure.
Applicant cites KSR and argues that the rejection is distorted by hindsight and ex post reasoning. In response to applicant’s argument that the examiner’s conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant’s disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Here, the rationale begins with Mars’s own express recommendation to expand its venom-sensing principle to other venom fractions from different animal species. The subsequent modifications are derived from the express teachings of the cited references, not from an unsupported roadmap reconstructed from the specification.
Applicant’s remarks emphasize differences in complete device architecture but do not identify evidence that the specific proposed modifications would have been inoperative. The rejection provides a reference-supported expectation of success. The cited references collectively demonstrate that the proposed modifications involve known electrochemical architectures, known antibody-immobilization chemistries, known multispecies venom-recognition reagents, and known assay organizations. Applicant has not identified a teaching away, technical incompatibility, or objective evidence demonstrating that the proposed combinations would have produced unexpected results.
Applicant states that the invention provides rapid differentiation of envenomation origin, supports selection of appropriate antivenom, avoids unnecessary treatments, and addresses an emergency clinical need. Those assertions do not establish patentability because the rejected claims do not recite the asserted differential diagnostic output, treatment decision, avoidance of multiple treatments, or clinical workflow. Further, to the extent those benefits naturally follow from broad or multispecies venom recognition, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Applicant does not present separate, limitation-specific arguments establishing patentability of claims 2–5, 7–9, or 11–13 apart from the arguments directed to their respective independent claims and the general reference-by-reference distinctions. Claims 2, 7, and 11 specify cysteamine HCl and PDITC, expressly addressed by Elshafey. Claims 5, 9, and 13 specify the GPH-GNP/cysteamine/PDITC/SPCE configuration, addressed by Mars, Wang, and Elshafey. Claim 3 specifies L. quinquestriatus and A. crassicauda, addressed by Ozkan together with the claim 1 combination. Claims 4 and 8 specify the listed snake species, addressed by Haidar together with the applicable base combination. Claim 12, under the compact-prosecution interpretation set forth in the action, selects L. quinquestriatus or A. crassicauda as the singular scorpion species of claim 10, and those species are expressly addressed by Ozkan. Accordingly, Applicant’s general arguments do not separately overcome the dependent-claim rejections.
Applicant’s arguments have been fully considered but are not persuasive. Applicant’s primary position depends upon importing into the claims requirements for a dual-electrode, label-free, species-resolving, single multiplex platform that simultaneously identifies all six listed snake venoms and both listed scorpion venoms. Those limitations are not recited in any pending claim. The updated rejections address the actual amended limitations. The rejection therefore does not depend upon any one reference disclosing the entire invention, bodily incorporation of complete devices, or hindsight reconstruction. It rests on express teachings, articulated reasons to combine, and demonstrated compatibility of the known elements.
Accordingly, the rejections of claims 1–13 under 35 U.S.C. §103 are maintained as revised in this action. The rejection of claims 1–13 under 35 U.S.C. §112(b) is maintained and updated as discussed above. The claim objections are withdrawn only to the extent the identified antecedent-basis issues were cured; the remaining grammatical objections are maintained or updated.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/E.O./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 August 3, 2026
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