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 .
Claim Objections
Claim 12 is objected to because of the following informalities: “transvers” in line 2 should be –transverse--. Appropriate correction is required.
Claim 14 is objected to because of the following informalities: “wail” in line 4 should be –wall--. Appropriate correction is required.
Claim 20 is objected to because of the following informalities: “transvers” in line 2 should be –transverse--. Appropriate correction is required.
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.
Claims 1-20 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.
Also, claim 1 recites “a reticular structure that is arranged in a microfluidic channel of a microfluidic device and extends in the directions transverse to the direction of fluid flow”. It is not clear as to what is meant by “a reticular structure that…extends in the directions transverse to the direction of fluid flow” since it is not clear what part of the reticular structure extends in the direction transverse to the direction of fluid flow. Also, the above-mentioned limitation refers to “directions” (i.e., multiple directions), and since there can only be 2 directions transverse to the direction of fluid flow (going in opposite directions), this does not make sense in the method.
Also, the limitation “a reticular structure that…extends in the directions transverse to the direction of fluid flow” is indefinite since it is a limitation that is defined by reference to an object (or subject), in this case, the direction of fluid flow, and the relationship between the limitation and the object is not sufficiently defined. In other words, the direction (or more specifically “directions”) of the reticular structure cannot be ascertained by the recited limitation (discussed further below).
Moreover, the direction of fluid flow is not clear, and thus the relationship between the limitation (i.e., the reticular structure’s directions) and the object (direction of fluid flow) is not sufficiently defined.
Furthermore, the limitation of “a reticular structure that…extends in the directions transverse….” (emphasis added) appears to indicate that the reticular structure extends in multiple directions that are transverse to one direction of fluid flow, which does not make sense in the claim.
Examiner notes that while the present claim 1 is directed to a method, the limitation of a “a reticular structure that…extends in the directions transverse to the direction of fluid flow” refers to a structure, and the structure as claimed is indefinite for the reasons set forth below.
For further explanation, see MPEP 2173.05(b), under the subheading “II. REFERENCE TO AN OBJECT THAT IS VARIABLE MAY RENDER A CLAIM INDEFINITE”, a portion of which is provided hereby below.
A claim may be rendered indefinite when a limitation of the claim is defined by reference to an object and the relationship between the limitation and the object is not sufficiently defined. That is, where the elements of a claim have two or more plausible constructions such that the examiner cannot readily ascertain positional relationship of the elements, the claim may be rendered indefinite. See, e.g., Ex parte Miyazaki, 89 USPQ2d 1207 (Bd. Pat. App. & Inter. 2008) (precedential) and Ex parte Brummer, 12 USPQ2d 1653 (Bd. Pat. App. & Inter. 1989). In Miyazaki, the Board held that claims to a large printer were not sufficiently definite because:
The language of claim 1 attempts to claim the height of the paper feeding unit in relation to a user of a specific height who is performing operations on the printer.... Claim 1 fails to specify, however, a positional relationship of the user and the printer to each other.
Miyazaki, 89 USPQ2d at 1212. In Brummer, the Board held that a limitation in a claim to a bicycle that recited “said front and rear wheels so spaced as to give a wheelbase that is between 58 percent and 75 percent of the height of the rider that the bicycle was designed for” was indefinite because the relationship of parts was not based on any known standard for sizing a bicycle to a rider, but on a rider of unspecified build. Brummer, 12 USPQ2d at 1655.
In the present case, the limitation “a reticular structure that…extends in the directions transverse to the direction of fluid flow” is indefinite since it is a limitation (i.e., the reticular structure’s directions) that is defined by reference to an object (i.e., the direction of fluid flow), and the relationship between the limitation and the object is not sufficiently defined since the direction of fluid flow changes during use.
Moreover, the direction of fluid flow is not provided in the claim, which thus does not provide a reference point for the reticular structure’s direction.
What part of the reticular structure is being referred to is also not provided or defined in the claim, which introduces vagueness in itself, and it also introduces vagueness since the reticular structure’s directions and the fluid flow direction do not provide clear reference points for each other. Additionally, the reference to the reticular structure’s multiple directions further add complexity to the vagueness mentioned above.
Claim 1, lines 1-2, recites a “method for the immobilization of one or more cells (20) under the fluid flow (F) conditions, in the context of a bioassay…” It is not clear as to what is meant by “in the context of a bioassay”. Does the claim require a bioassay? Or does the claim encompass merely immobilizing a cell, without requiring a bioassay? If the claim requires a bioassay, is the cell being used in the bioassay?
Claim 3 recites “a size of each window (18) along its respective maximum extension is not more than 90% of a diameter of the trapped cell, and wherein a size of each window along its respective minimum extension is at least 10% of the diameter of the trapped cell to be trapped.”
This limitation is indefinite since it is a limitation (i.e., the size of each window….”) that is defined by reference to an object (i.e., the diameter of a trapped cell), and the relationship between the limitation and the object is not sufficiently defined. The diameter of a trapped cell is not defined, and depends on the cell. Thus the size of the window as recited cannot be ascertained.
Examiner notes that while the present claim 3 is directed to a method, the limitation of a diameter of a window as recited refers to a structure, and the structure as claimed is indefinite for the reasons set forth above.
Claim 4 recites in the last 4 lines of the claim, “wherein a smallest extension of the concave cell receiving surface transverse to the fluid flow (F) is at least 1.1 times a diameter of the trapped cell, and wherein a smallest extension of the concave cell receiving surface transverse to the fluid flow is at most 10 times the diameter of the trapped cell.”
This limitation is indefinite since it is a limitation (i.e., the smallest extension of the concave cell….”) that is defined by reference to an object (i.e., the diameter of the trapped cell), and the relationship between the limitation and the object is not sufficiently defined. The diameter of a trapped cell is not defined, and depends on the cell. Thus the size of the window as recited cannot be ascertained.
Examiner notes that while the present claim 4 is directed to a method, the limitation of the smallest extension of the concave cell refers to a structure, and the structure as claimed is indefinite for the reasons set forth above.
Claim 6, in the last line, recites “the incoming fluid flow”. The claim lacks sufficient antecedent basis for this limitation.
Claim 7, in lines 5-7, recites “a cell trapping element having a reticular structure and being arranged in the microfluidic channel (30) such that the reticular structure extends in the directions transverse to the fluid flow direction (F)…”
This limitation is vague for the same reasons discussed above regarding the limitation in claim 1 that recites “a reticular structure that is arranged in a microfluidic channel (30) of a microfluidic device and extends in the directions transverse to the direction of the fluid flow (F)…”, which will not be repeated for purposes of brevity.
Claim 7 recites “fluid flow (F) conditions” in line 2. However, lines 3-4, recites ‘fluid flow direction (F)”. This introduces vagueness as to what the symbol “(F)” means. Does it mean fluid flow, or does it mean fluid flow direction? To avoid vagueness, Examiner recommends that the symbol “(F)” be removed.
Claim 16 recites in line 2 “the concave cell receiving surface”. The claim lacks sufficient antecedent basis for this limitation. [For examination purposes, claim 16 is interpreted as if it depends from claim 4, which would provide antecedent basis for this limitation.]
Claim 16 recites “wherein the smallest extension of the concave cell receiving surface transverse to the fluid flow (F) is at least 1.3 times the diameter of the trapped cell”.
This limitation is indefinite since it is a limitation (i.e., the smallest extension of the concave cell….”) that is defined by reference to an object (i.e., the diameter of the trapped cell), and the relationship between the limitation and the object is not sufficiently defined. The diameter of a trapped cell is not defined, and depends on the cell. Thus the size of the window as recited cannot be ascertained.
Claim 17 recites in line 2 “the concave cell receiving surface”. The claim lacks sufficient antecedent basis for this limitation. [For examination purposes, claim 17 is interpreted as if it depends from claim 4, which would provide antecedent basis for this limitation.]
Claim 17 recites “wherein the smallest extension of the concave cell receiving surface transverse to the fluid flow (F) is at least 1.5 times the diameter of the trapped cell.”
This limitation is indefinite since it is a limitation (i.e., the smallest extension of the concave cell….”) that is defined by reference to an object (i.e., the diameter of the trapped cell), and the relationship between the limitation and the object is not sufficiently defined. The diameter of a trapped cell is not defined, and depends on the cell. Thus the size of the window as recited cannot be ascertained.
The remaining claims are rejected since they depend from claim 1, which is rejected for the reasons set forth above.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-3, 7-9, 12, 14-15 and 17-20 is/are rejected under 35 U.S.C. 102(a(s) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over US 20190145980 (hereinafter “Kang”).
Applicant’s claim 1 recites:
a method for the individual immobilization of one or more cells under fluid flow conditions, in the context of a bioassay,
comprising for each cell the step of trapping said cell by means of a cell trapping element,
which comprises a reticular structure that is arranged in a microfluidic channel of a microfluidic device and extends in the directions transverse to the direction of fluid flow,
wherein the reticular structure is composed of a plurality of struts that define a plurality of windows allowing fluid to flow through said windows.
Kang discloses the following, which is relevant to Applicant’s claims.
“The invention relates to methods of detection, capture, isolation and targeting of cancer cells for example circulating tumor cells (CTCs) using carbohydrate recognition domain of a lectin.” Abstract (emphasis added).
“In some embodiments, the lectin molecule is attached to a surface for example, a solid surface. The surface can be made from a wide variety of materials and in a variety of formats. For example, in the form of beads (including polymer microbeads, magnetic microbeads, and the like), filters, fibers, screens, mesh, tubes, hollow fibers, porous scaffolds, plates, channels, other substrates commonly utilized in assay formats, and any combinations thereof. Examples of surfaces include, but are not limited to, nucleic acid scaffolds, protein scaffolds, lipid scaffolds, dendrimers, microparticles or microbeads, nanotubes, microtiter plates, medical apparatuses (e.g., needles or catheters) or implants, dipsticks or test strips, microchips, filtration devices or membranes, diagnostic strips, hollow-fiber reactors, microfluidic devices, living cells and biological tissues or organs, extracorporeal devices, mixing elements (e.g., spiral mixers). The surface can be made of any material, including, but not limited to, metal, metal alloy, polymer, plastic, paper, glass, fabric, packaging material, biological material such as cells, tissues, hydrogels, proteins, peptides, nucleic acids, and any combinations thereof.” Para. 0066 (emphasis added).
“The captured CTC can remain bound on the lectin molecule during detection and/or analysis, or be isolated from it prior to detection and/or analysis. In some embodiments, a composition comprising a peptide comprising the CRD region of a lectin is linked to a detectable label for example an “imaging agent” or a “contrast agent”. As used herein, the term “detectable label” refers to a agent capable of producing a detectable signal indicative of the presence of a target for example a cancer cells, CTCs, solid tumor, metastatic tumor. Detectable labels include any composition detectable by spectroscopic, photochemical, biochemical, immunochemical, electrical, optical or chemical means. Suitable labels include fluorescent molecules, radioisotopes, nucleotide chromophores, enzymes, substrates, chemiluminescent moieties, bioluminescent moieties, and the like. As such, a label is any composition detectable by spectroscopic, photochemical, biochemical, immunochemical, electrical, optical or chemical means needed for the methods and compositions described herein.” Para. 0092 (emphasis added).
Thus, Kang teaches a method for the individual immobilization of one or more cells under fluid flow conditions, in the context of a bioassay, [see Kang abstract] comprising
for each cell the step of trapping said cell by means of a cell trapping element which comprises a reticular structure that is arranged in a microfluidic channel of a microfluidic device
[see Kang in para. 0066 disclosing use of a screen or mesh, in combination with
a channel, as well as microfluidics and filtration devices (wherein the Kang screen or mesh is equivalent to Applicant’s claimed cell trapping element); and see para. 0066 disclosing lectin attached to the screen or mesh surface; and see para. 0092 disclosing capturing (CTC) cells via the attached lectin];
[see para. 0066 disclosing a mesh or screen, which is understood to have a reticular structure];
[Examiner notes that this interpretation of the claimed reticular structure is consistent with Applicant’s description of a reticular structure in the specification in the Pre-Grant Publication US 20250102505, which discloses the following:
“the reticular structure is composed of a plurality of struts that define a plurality of windows (openings), which allow fluid to flow through said windows” (para. 0012);
“the reticular structure defines a mesh with a mesh size adapted to retain a cell but to support fluid flow directly around the cell and through the windows (openings) in the mesh” (para. 0013)]
and extends in the directions transverse to the direction of fluid flow
[see paras. 0066 and 0092, wherein it is understood that a screen is used in directions transverse to the direction of fluid flow in order to wherein achieve the disclosed function of capturing cells or filtering to capture cells; alternatively, it would have been obvious to one skilled in the art that the screen be used in directions transverse to the direction of fluid flow as this would have resulted in the predictable outcome of achieving the disclosed function of capturing cells or filtering to capture cells],
wherein the reticular structure is composed of a plurality of struts that define a plurality of windows allowing fluid to flow through said windows [see para. 0066 disclosing a mesh or screen].
Applicant’s claim 2 recites: the method of claim 1, wherein a fluid velocity at a location of the trapped cell or at a location of the reticular structure is set to a value of at least about 1 mm/s.
This velocity falls within a workable or optimum range. Where the general conditions of a claim are disclosed, such as here, discovering a workable or optimum range of a parameter of the invention (in this case, the fluid velocity as claimed) requires routine skills in the art.
Applicant’s claim 3 recites: the method of claim 1, wherein a size of each window along its respective maximum extension is not more than about 90% of a diameter of the trapped cell, and wherein a size of each window along its respective minimum extension is at least 10% of the diameter of the trapped cell to be trapped.
The sizes of each window as recited fall within a workable or optimum range. Where the general conditions of a claim are disclosed, such as here, discovering a workable or optimum range of a parameter of the invention (in this case, the sizes of each window as recited) requires routine skills in the art.
As to claim 7, Kang teaches a microfluidic device for the individual immobilization of one or more cells under fluid flow conditions of a bioassay, comprising
a microfluidic channel supporting continuous fluid flow along a fluid flow direction;
and a cell trapping element having a reticular structure and being arranged in the microfluidic channel
[see Kang in para. 0066 disclosing use of a screen or mesh, in combination with
a channel, as well as microfluidics and filtration devices (wherein the Kang screen or mesh is equivalent to Applicant’s claimed cell trapping element); and see para. 0066 disclosing lectin attached to the screen or mesh surface; and see para. 0092 disclosing capturing (CTC) cells via the attached lectin]
such that the reticular structure extends in the directions transverse to the fluid flow direction
[see paras. 0066 and 0092, wherein it is understood that a screen is used in directions transverse to the direction of fluid flow in order to wherein achieve the disclosed function of capturing cells or filtering to capture cells; alternatively, it would have been obvious to one skilled in the art that the screen be used in direction transverse to the direction of fluid flow as it would have resulted in a predictable outcome of achieving the disclosed function of capturing cells or filtering to capture cells],
wherein the reticular structure is composed of a plurality of struts that define a plurality of windows allowing fluid to flow through said windows, such that cells can be held trapped by the cell trapping element under fluid flow conditions
[see para. 0066 disclosing a mesh or screen, which is understood to have a reticular structure composed of struts that define a plurality of windows]
[Examiner notes that this interpretation of the claimed reticular structure is consistent with Applicant’s description of a reticular structure in the specification in the Pre-Grant Publication 20250102505, which discloses:
in para. 0012 that “the reticular structure is composed of a plurality of struts that define a plurality of windows (openings), which allow fluid to flow through said windows”;
and in para. 0013 that “the reticular structure defines a mesh with a mesh size adapted to retain a cell but to support fluid flow directly around the cell and through the windows (openings) in the mesh”].
Claim 8 recites: the device of claims 7, wherein a diameter of each strut of the reticular structure is in the range of about 0.2 pm to about 10 pm.
The diameter of each strut as recited falls within a workable or optimum range. Where the general conditions of a claim are disclosed, such as here, discovering a workable or optimum range of a parameter of the invention (in this case, the diameter of each strut as recited) requires routine skills in the art.
Claim 9 recites: the device of claim 7, wherein a size of each window along its respective maximum extension is at most about 15 pm, and wherein a size of each window along its respective minimum extension is at least about 1 pm.
The sizes of each window as recited fall within a workable or optimum range. Where the general conditions of a claim are disclosed, such as here, discovering a workable or optimum range of a parameter of the invention (in this case, the sizes of each window as recited) requires routine skills in the art.
Claim 12 recites: the device of claim 7, wherein the microfluidic channel has a cross section transverse to the direction of the fluid flow in the range of about 0.2 104 pm2 to about 20 104 pm2.
The cross section of the microfluidic channel as recited falls within a workable or optimum range. Where the general conditions of a claim are disclosed, such as here, discovering a workable or optimum range of a parameter of the invention (in this case, the cross section of the microfluidic channel as recited) requires routine skills in the art.
Claim 14 recites: the device of claim 7, wherein the reticular structure is attached with one end thereof to an inner surface of a first microfluidic channel wall and with another end thereof to an inner surface of a second microfluidic channel wall substantially opposite to the first microfluidic channel wail.
As mentioned above, Kang in general discloses a filter in combination with a microfluidic channel. It would have been obvious to one skilled in the art that attachment of the filter to a microfluidic channel for its disclosed use can involve well known means such as attachment at one end to an inner surface of a microfluidic channel wall, and attachment at another end to a second microfluidic channel wall opposite the first microfluidic channel wall. This design choice would have resulted in a predictable outcome of attachment of the filter in the microchannel for its use as disclosed by Kang.
Claim 15 recites: the device of claim 14, wherein the reticular structure of the cell trapping element being compressed between inner surfaces of the first and second microfluidic channel wall.
It would have been obvious to one skilled in the art that the Kang filter can be attached between opposite microchannel walls, as discussed in claim 14, such that the filter is compressed between inner surfaces of the microchannel walls. This design choice would have resulted in a predictable outcome of a secured attachment of the filter in the microchannel for its use as disclosed.
Claim 19 recites: the device of claim 7, wherein the size of each window along its respective maximum extension is at most about not more than 8 pm, and wherein the size of each window along its respective minimum extension is at least about 7 pm.
The sizes of each window as recited fall within a workable or optimum range. Where the general conditions of a claim are disclosed, such as here, discovering a workable or optimum range of a parameter of the invention (in this case, the sizes of each window as recited) requires routine skills in the art.
Claim 20 recites: the device of claim 7, wherein the microfluidic channel has a cross section transvere to the direction of the fluid flow in the range of about 1-104 pm2 to about 5-104 pm2.
The cross section of the microfluidic channel as recited falls within a workable or optimum range. Where the general conditions of a claim are disclosed, such as here, discovering a workable or optimum range of a parameter of the invention (in this case, the cross section of the microfluidic channel as recited) requires routine skills in the art.
Claim(s) 5 is/are rejected under 35 U.S.C. 103 as obvious over US 20190145980 (hereinafter “Kang”) in view of US 20130273053 (hereinafter “Schwaeble”).
Kang, discussed above, is silent as to determining the kinetics of the binding of a ligand to the immobilized cells.
However, determining binding kinetics is known in the art, as shown by Schwaeble.
More specifically, Schwaeble discloses that saturation binding kinetics were determined by staining DTLacO cells expressing antibody binding MASP-1 or MASP-3 with various concentrations of fluorescent-labeled soluble antigen. Para. 0670.
It would have been obvious to one skilled in the art to utilize the Kang binding assay to determine binding kinetics as known in the art for study, as exemplified by Schwaeble.
Claim(s) 10 is/are rejected under 35 U.S.C. 103 as obvious over US 20190145980 (hereinafter “Kang”) in view of US 20190374947 (hereinafter “Shrivastava”).
Kang, discussed above, is silent as to the device of claim 7, further comprising a gold layer covering part of an inner surface of a microfluidic channel wall, wherein the reticular structure of cell trapping element is attached to the gold layer.
However, Shrivastava discloses a microfluidic device for the separation and immobilization of one or more cells (see abstract). Shrivastava discloses that a microchannel of the device may be comprised of any biocompatible material such as gold (para. 0056).
It would have been obvious to one of ordinary skills in the art to provide gold in the Kang microfluidic channel since it is a biocompatible material known for use in a microchannel, as taught by Shrivastava, as would be desirable in the Kang device for the immobilization of cells for analysis.
Allowable Subject Matter
Claims 4, 6, 11, 13, 16 and 17 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
Conclusion
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/Ann Montgomery/Primary Examiner, Art Unit 1678