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 .
Continued Examination
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 May 27, 2026 has been entered.
Status of the Claims
Claim 1 has been amended; claim 8 has been cancelled; and claims 9-22 have been withdrawn. Claims 1-7 and 23 are examined herein.
Status of the Rejection
New grounds of specification objection as outlined below.
New grounds of claim objection as outlined below.
The claim interpretations under 35 U.S.C. § 112(f) from the previous office action are essentially maintained and modified in response to the amendment.
All 35 U.S.C. § 103 rejections from the previous office action are essentially maintained and modified in response to the amendment.
Specification
Applicant amended the specification by adding “Appendix to the specification”, which was not present in the original specification, thus it is objected to the amendment. The document of “Appendix to the specification” should be a part of the Applicant Arguments/Remarks instead of appendix to the specification.
Claim Objection
Claims 1 and 7 are objected to because of the following informalities:
Claim 1: please amend “a single biological cell-present” – a single biological cell [[-]] present--; “the cell” to – the single biological cell--; “said cell” to – said single biological cell--; “said sampling means” to -- said sampling and injecting means--.
Claim 7: please amend “the sampling means” to -- the sampling and injecting means--.
Appropriate correction is required.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
Claim 1, “a measuring means for measuring an electrical property of a single biological cell present in a solution”, is being interpreted under 35 U.S.C. 112(f) . Prong 1: a measuring means for (“means for”), prong 2: measuring an electrical property of a single biological cell present in a solution … (functional language), prong 3: sufficient structure for performing the function not recited. Therefore, claim 1 invokes 112(f). The corresponding structure for performing the functions is described in the specification (paragraph [0154] in PGPub) such as “The measuring means can be a handheld portable multimeter, and electrical resistance meter, an electrical capacitance meter, an electrical voltage meter, an electrophysiology amplifier, etc.”
Claim 1, “a sampling and injecting means configured for penetration of a cell membrane for sampling said solution, a membrane of the single biological cell, and/or an intracellular fluid of the cell and for injecting a material into said cell”, is being interpreted under 35 U.S.C. 112(f) . Prong 1: a sampling and injecting means (“means”), prong 2: configured for penetration of a cell membrane for sampling said solution, a membrane of the single biological cell, and/or an intracellular fluid of the cell and for injecting a material into said cell (functional language), prong 3: sufficient structure for performing the function not recited. Therefore, claim 1 invokes 112(f). The corresponding structure for performing the functions is described in the specification (paragraph [0142] in PGPub) such as sampling means (32) comprises a micropipette (43) having a sharp tip (45) (made from glass, plastic, carbon fiber, silicon, etc.) filled with an electrolyte.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-3, 7 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Mor et al. (WO2020077244A1), and in view of Vasylyev et al. (US20050255446A1).
Regarding claim 1, Mor teaches a detection apparatus (an apparatus comprising a bore pipette as shown in Fig.1 [Ln 7-24 on page 13]) for testing biological cells (the large bore pipettes for measuring cell resistance, real-time measurement of membrane resistance and/or capacitance [Ln 11-12, 23-24 on page 13]; thus the disclosed apparatus is configured to perform the intended use of testing biological cells), the apparatus comprising:
a measuring means (an electrical resistance meter connected to the injection pipette tip [claim 1]; Fig.1 shows an electrophysiological amplifier 6 connected to the electrode wire of the injection micropipette 2 [Ln 30-34 on page 16]; measurement device comprising the electrical resistance meter and the electrophysiological amplifier 6 that is connected to the electrode wire of the pipette is deemed as the measuring means) for measuring an electrical property of a single biological cell present in a solution (for measuring membrane resistance [Ln 11-12, 23-24 on page 13] of a single biological cell 1 present in a petri dish with extracellular solution 7 as shown in Fig.1);
a sampling and injection means (a pipette tip as shown in Fig.1; an injection pipette having a tip [claims 1 and 3]; a commercial egg/cell glass injection pipette with a tip curved at 30 degrees was attached to the right manipulator [Ln 27-28 on page 16]; the pipette tip is deemed as the sampling and injection means) configured for penetration of a cell membrane for sampling a membrane of the single biological cell and for injecting a material into said cell (the tip is configured to penetrate a membrane of the cell, and wherein the electrical resistance meter is connected directly or indirectly to the injection pipette tip [claim 1]; Fig.1 shows the pipette tip for sampling a membrane of the single biological cell 1 for measuring membrane resistance and/or capacitance [Ln 18-24 on page 13; Ln 3-6 on page 12]; injecting material into the cell through the injection pipette tip [Ln 5-6 on page 5]; Material can be injected into the cell via an injection micropipette 2 that is coupled to an electrophysiological amplifier 6 [Ln 10-12 on page 17]. Thus, the pipette tip of the injection micropipette is configured to perform the claimed functions), and
an adaptor (Figs.15A-15B show an adaptor for holding a pipette having a wire connected to the electrode wire on one end and connected to an alligator clip of a cable that can connect to one or more measuring devices [Ln 25-28 on page 6]) distinct from and located between said sampling and injecting means (pipette tip) and said measuring means (measurement device such as electrical resistance meter and/or amplifier disposed outside of the pipette) surrounding an electrically conductive material (the pipette having an electrical wire in the pipette lumen [Ln 18-22 on page 13]; electrolyte in the pipette [Ln 17 on page 12]; both the electrical wire and the electrolyte in the pipette are deemed as the electrically conductive material).
Mor is silent to wherein the adaptor is an electrically insulating component having resistance to an alkaline solution of pH of 8 to 11 containing chlorine ions.
Vasylyev teaches a perfusion system and apparatus for high throughput patch clamp measurements. Each patch clamp configuration comprises a cell sealed to a pipette (title and abstract). Fig.4C shows the single pipette 40 is held in place by a polyurethane (or other polymer or similar material) tube 54 [para. 0079], and the polyurethane tube 54 surrounds an electrically conductive material (electrode 4 and solution inside the pipette 40). Thus, Vasylyev teaches an adaptor (polyurethane tube 54 in Fig.4C) for holding a pipette 40. The adaptor made of polyurethane is deemed as the electrically insulating component having resistance to an alkaline solution of pH 8 to 11 containing chlorine solutions. Note that the disclosed polyurethane material of the electrically insulating component is the same as that used in the instant application, as evidenced by the last column in Table 3 of the instant specification.
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 adaptor in Mor to an adaptor made of polyurethane, which is distinct from and located between the sampling and injecting means and the measuring means surrounding the electrically conductive material, as taught by combined Mor and Vasylyev, since Vasylyev teaches the adaptor made of polyurethane would be suitable for holding the pipette in place for measuring electrical properties of the cell sealed to the pipette [para. 0079 and abstract in Vasylyev]. Furthermore, the selection of a known material, which is based upon its suitability for the intended use, is within the ambit of one of ordinary skill in the art [MPEP § 2144.07].
Since the disclosed electrically insulating component is made of polyurethane, which is the same as the material of the electrically insulating component used in this instant application (see the last column in Table 3 in instant specification), it is contended that the electrically insulating component of the prior art also has resistance to an alkaline solution of pH 8 to 11 containing chlorine ions. Accordingly, products of identical chemical composition cannot have mutually exclusive properties, and thus, the claimed property (i.e. the electrically insulating component has resistance to an alkaline solution of pH 8 to 11 containing chlorine ions), is necessarily present in the prior art material. The courts have held that “[p]roducts of identical chemical composition cannot have mutually exclusive properties.” A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01 (II).
Regarding claim 2, modified Mor teaches the detection apparatus of claim 1, and Mor teaches wherein said electrical property is selected from the group consisting of membrane resistance (membrane resistance [Ln 5 on page 10; Ln 23-24 on page 13]), wherein said measuring means comprises an electrical resistance meter (an electrical resistance meter is connected directly or indirectly to the injection pipette tip [claim 1; Ln 12-14 on page 26]).
Regarding claim 3, modified Mor teaches the detection apparatus of claim 1, and Mor teaches wherein the electrically conductive material comprises a metal (electrical wire [Ln 20-22 on page 13]; electrical conductors include metal [e.g., copper, gold, silver] [Ln 23-26 on page 8]; metal wire selected from a silver wire and a copper wire [claim 9]) and/or a conductive fluid (electrical conductors include fluid [e.g., a liquid or a gel] containing charged particles [e.g., electrolytes] [Ln 25-27 on page 8]; the electrical conductor is an electrolyte solution [claim 10]).
Regarding claim 7, modified Mor teaches the detection apparatus of claim 1, and Mor teaches wherein the sampling and injecting means comprises a micropipette tip (These pipettes can have bore diameters that are about 4 micrometers to about 10 micrometers, or about 4 micrometers to about 7 micrometers, or about 4 micrometers to about 6 micrometers, or about 4 micrometers, or about 5 micrometers, or about 6 micrometers [Ln 14-17 on page 13]; an injection pipette having a tip [claim 1]; glass injection pipette with a tip curved at 30 degrees was attached to the right micromanipulator [Ln 28-29 on page 16]).
Regarding claim 23, modified Mor teaches the detection apparatus of claim 1, and the limitations “wherein said resistance to said alkaline solution comprises at least one property selected from the group consisting of resistance to formation of microcracks for at least 1 minute upon exposure to said alkaline solution; resistance to electrical insulation failure for at least 12 minutes upon exposure to said alkaline solution; and resistance to visible structural integrity failure for at least 20 minutes upon exposure to said alkaline solution” are inherent characteristic of the adaptor made of polyurethane. Since the disclosed electrically insulating component is made of polyurethane, which is the same as the material of the electrically insulating component used in this instant application (see the last column in Table 3 in instant specification), it is contended that the electrically insulating component of the prior art also has the same resistance as that in the instant application. Accordingly, products of identical chemical composition cannot have mutually exclusive properties, and thus, the claimed property (i.e. said resistance to said alkaline solution comprises at least one property selected from the group consisting of resistance to formation of microcracks for at least 1 minute upon exposure to said alkaline solution; resistance to electrical insulation failure for at least 12 minutes upon exposure to said alkaline solution; and resistance to visible structural integrity failure for at least 20 minutes upon exposure to said alkaline solution), is necessarily present in the prior art material. The courts have held that “[p]roducts of identical chemical composition cannot have mutually exclusive properties.” A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01 (II).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Mor and Vasylyev, as applied to claim 3 above, and in view of Cliffel et al. (US20050014129A1).
Regarding claim 4, modified Mor teaches the detection apparatus of claim 3, and Mor further teaches wherein the electrically conductive material comprises silver (a silver wire [claim 9]).
Mor is silent to wherein the silver wire is coated with chloride.
Cliffel teaches an apparatus for detecting at least one analyte of interest either produced or consumed by a plurality of cell (abstract) and further teaches wherein the electrode is coated with silver chloride (A 2 mm wide pad 3101 of platinum on the glass substrate is coupled to interdigitated microstrip electrodes 3102 and 3103 that are five microns wide and separated by five microns and thus forming a plurality of fingers. Each of the individual fingers can be coated with silver/silver chloride [para. 0251]).
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 silver wire in modified Mor to silver wire coated with chloride, as taught by Cliffel, since Cliffel teaches silver coated with chloride as a suitable alternative electrode material for testing biological cells [para. 0251 and abstract]. Furthermore, the selection of a known material, which is based upon its suitability for the intended use, is within the ambit of one of ordinary skill in the art [MPEP § 2144.07].
Allowable Subject Matter
Claims 5-6 objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter.
Regarding claim 5, modified Mor teaches the detection apparatus of claim 3.
Note that claim 1 recites “an electrically insulating component distinct from and located between said sampling and injecting means and said measuring means surround an electrically conductive material”, and claim 5 further recites “wherein the electrically conductive material comprises a mineral oil”. Thus, claim 5 requires the electrically insulating component (which is the adaptor made of polyurethane as outlined in the rejection of claim 1 above) surrounding the electrically conductive material, which comprises a mineral oil. Mor teaches a droplet of commercial MII medium was placed on a petri dish. Mineral oil was added until it fully covered the droplet to prevent droplet evaporation. A commercial egg/cell glass holding pipette with a tip curved at 30 degrees was attached to the left micromanipulator. A commercial egg/cell glass injection pipette with a tip curved at 30 degrees was attached to the right manipulator. Of note, the injection pipette was prefilled with MII medium and was attached to an electrophysiological headstage (available, e.g., from Axon instruments). A silver wire originating from the headstage was in contact with the MII medium in the injection pipette [Ln 22-32 on page 16]. Thus, the injection pipette was prefilled with MII medium, and the mineral oil covers the MII medium of the petri dish. Mor and other prior art of the record does not teach and/or suggest the adaptor of the injection pipette is filled with a mixture of electrolyte and mineral oil, thus does not teach and/or suggest the adaptor surrounding the electrically conductive material comprising a mineral oil required in claim 5. Claim 6 is allowable because claim 6 depends from claim 5.
As allowable subject matter has been indicated, applicant's reply must either comply with all formal requirements or specifically traverse each requirement not complied with. See 37 CFR 1.111(b) and MPEP § 707.07(a).
Response to Arguments
Applicant's arguments, see Remarks Pgs. 5-7, filed 5/27/2026, with respect to the 35 U.S.C. § 103 rejections have been fully considered, but are not persuasive.
Applicant’s Argument #1:
Regarding claim 1, Applicant argues at pages 5-6 that Mor does not teach or suggest the feature " ... wherein the adaptor is an electrically insulating component having resistance to an alkaline solution of pH of 8 to I I containing chlorine
ions ... ". Vasylyev does use an adaptor in the form of a polyurethane tube for holding a pipette, there is no teaching or suggestion in the prior art to Vasylyev that the material of the tube was selected due to its resistance to an alkaline solution of pH of 8 to 11 containing chlorine ions, or indeed that the tube was intended for exposure to such an alkaline solution. Rather, the material of the tube was selected due to other advantages in terms of other physical and/or chemical properties of polyurethane. Moreover, para. [0079] to Vasylyev discloses that the tube which holds the pipette in place may be made of polyurethane or other polymer of similar material, with no teaching as to the required properties of the 'other polymer' which would define it as a 'similar material'. Accordingly, one of ordinary skill in the art, upon reading the disclosure of Vasylyev would not understand that there is any requirement to specifically use a material having a required alkaline resistance in accordance with the definition of claim 1, but rather would understand that any of an undefined number of polymers may be used, which may incidentally have the required alkaline resistance, but not as an essential feature.
Examiner’s Response #1:
Applicant’s arguments have been fully considered, but are not persuasive. Firstly, Applicant admitted that Vasylyev discloses that the tube which holds the pipette in place may be made of polyurethane or other polymer of similar material. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use an adaptor made of polyurethane to hold the micropipette of Mor. Although Vasylyev teaches the adaptor may be made of polyurethane or other polymer of similar material, choosing from a finite number of identified, predictable solutions (polyurethane or other polymer of similar material), with a reasonable expectation for success, is likely to be obvious to a person if ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143 (I)(E).
Secondly, “having resistance to an alkaline solution of pH of 8 to 11 containing chlorine ions ..” is an inherent property of the adaptor made of polyurethane. Since the disclosed electrically insulating component is made of polyurethane, which is the same as the material of the electrically insulating component used in this instant application (see the last column in Table 3 in instant specification), it is contended that the electrically insulating component of the prior art also has resistance to an alkaline solution of pH 8 to 11 containing chlorine ions. Accordingly, products of identical chemical composition cannot have mutually exclusive properties, and thus, the claimed property (i.e. the electrically insulating component has resistance to an alkaline solution of pH 8 to 11 containing chlorine ions), is necessarily present in the prior art material. The courts have held that “[p]roducts of identical chemical composition cannot have mutually exclusive properties.” A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01 (II).
Applicant’s Argument #2:
Applicant argues at pages 6-7 that Mor does not teach or suggest the requirement to identify a material which is not resistant to an alkaline solution of pH 8 to 11 containing chloride ions at all. Mor teaches use of polycarbonate, which is not resistant to an alkaline solution as defined in claim 1, while Vasylyev teaches use of polyurethane, which, although resistant to an alkaline solution
of pH 8 to 11 containing chloride ions, is sensitive to an alkaline solution containing chloride ions, such as bleach (sodium hypochlorite), at the standard concentration of a commercial bleach solution, having a pH of greater than 11. Therefore, one of ordinary skill in the art, upon seeking a material having resistance to bleach, would be expected to refer to data relating to a standard commercial bleach solution, and as such, would not be motivated to select polyurethane as such a material. Furthermore, claim 1 as currently amended is directed to a sampling and injecting means which is configured to pierce a cell membrane, and enter the cell, as well as to inject a material into the cell. In clear contrast, Vasylyev discloses a patch-clamp system, comprising a blunt-tipped
micropipette, which is not configured to penetrate a cell membrane and thus cannot enter the cell, directly measure the inside of a cell, or inject sperm ( or any other substance) into the cell. Therefore, the system of Vasylyev is entirely different from that of Mor such that one of ordinary skill in the art would not be motivated to combine the two in order to arrive at the claimed invention.
Examiner’s Response #2:
Applicant’s arguments have been fully considered but are not persuasive. Firstly, Applicant admits that Vasylyev teaches use of an adaptor made of polyurethane to hold the pipette (see Applicant’s Argument #1 above) and the adaptor made of polyurethane is resistant to an alkaline solution of pH 8 to 11 containing chloride ions (see Applicant’s Argument #2 above), thus the disclosed adaptor made of polyurethane reads on the claimed limitation: “wherein said electrically insulating component (which is the adaptor made of polyurethane) has resistance to an alkaline solution of pH 8 to 11 containing chloride ions”.
Secondly, the rejection of claim 1 is under 103 instead of 102, and Mor already teaches the sampling and injecting means and the modification by Vasylyev is to modify the adaptor of Mor to adaptor made of polyurethane, thus the modified apparatus is directed to a sampling and injecting means which is configured to pierce a cell membrane, and enter the cell, as well as to inject a material into the cell.
Examiner suggests applicant to amend claim 1 by incorporating the limitations of claim 5.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHIZHI QIAN whose telephone number is (571)272-3487. The examiner can normally be reached Monday-Thursday 8:00 am-5:00 pm.
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/SHIZHI QIAN/Primary Examiner, Art Unit 1795
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