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 1-10, 13-20, and 22-23 are currently pending.
Claims 10, 13, 16-17, and 23 are amended.
Claims 11-12, 21, and 24-25 are cancelled.
Claims 1-10, 13-20, and 22-23 have been considered on the merits.
Specification
The use of the term GelMA™ throughout the examples, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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 1-10, 13-20, and 22-23 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 contains the steps of providing cell masses, subjecting the cell masses to an imaging device, providing a biomaterial formulation, acquiring images of the cell masses to be encapsulated in the biomaterial, determining location and other information about the target cell masses, and finally mixing the formulation of the biomaterial with the target cell masses followed by inducing a formation of a network, gelation system, or scaffold for encapsulating and accommodating the target cell masses. The order of the recitation of steps is indefinite. It is not clear how the step of locating the target cell masses comes before the step of mixing the cell masses and the biomaterial together. The last step of mixing the target cell masses with the biomaterial would move the cell masses from the location that had been previously determined, therefore it is not clear how one would perform the step of mixing and actually achieve encapsulating the target cell masses that has been identified. The dependents of claim 1 are included in this rejection. Appropriate clarification is required.
Claim 1 recites the limitation "the corresponding compartment" in lines 11-12. There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites the phrase “followed by inducing a formation of a network, gelation system or scaffold for encapsulating and accommodating the target cell masses” in lines 12-13, which is indefinite. It is unclear by the recitation of “for encapsulating” whether or not the claim requires encapsulating the target cell masses or only requires inducing a formation of a network, gelation system or scaffold that may or may not encapsulate the target cell masses. Additionally, it is unclear what the term “accommodating” implies in relation to the target cell mass and the specification does not provide a definition for the term “accommodating”. Appropriate clarification is required.
Claim 10 recites the phrase “comprising a temperature control mechanism and a gas regulation mechanism for in-situ biomaterial encapsulation”, in lines 3-5, which is indefinite. It is unclear by the recitation of “for in-situ biomaterial encapsulation” whether or not the claim requires encapsulation of the target cell masses or only requires a temperature control mechanism and a gas regulation mechanism. Appropriate clarification is required.
Claim 4 recites the phrase “material or mixture that forms a network, gelation system or scaffold for encapsulating and accommodating the target cell masses” in lines 2-4, which is indefinite. It is unclear by the recitation of “for encapsulating” whether or not the claim requires encapsulating the target cell masses or only requires inducing a formation of a network, gelation system or scaffold that may or may not encapsulate the target cell masses. Additionally, it is unclear what the term “accommodating” implies in relation to the target cell mass and the specification does not provide a definition for the term “accommodating”. Appropriate clarification is required.
Claim 6 contains the trademark/trade name GelMA™. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe methacrylated gelatin and, accordingly, the identification/description is indefinite.
Claims 14 and 15 recite the limitation of a “image analysis algorithm”, which is indefinite. It is not clear what the metes and bounds of an image analysis algorithm would be. Additionally, the specification does not provide a definition of the image analysis algorithm. Appropriate clarification is required.
Claim 15 contains the phrase “wherein the image analysis algorithm is configured to differentiate the image signals from the target cell masses than those from the non-target cell masses or any noise from the background, and also calculate distance between the target cell masses and neighboring non-target cell masses”, which is indefinite. It is unclear how the phrase “and also calculate” limits the claims. It is not clear if the claim requires the image analysis algorithm to be “configured to” calculate or if the image analysis algorithm must calculate the distance between the target masses and non-target masses. Appropriate clarification is required.
Claim 15 is rendered indefinite for containing the phrase, “configured to” in line 2 which implies steps must occur to meet the limitation. However, no steps are recited making the claim indefinite in scope. Appropriate clarification is required.
Claim 16 contains the phrase “from about 30 to 2000 µm” in line 2, which is indefinite. It is unclear by the recitation of the phrase “from about” if the claimed range must be within 30 to 2000 µm or if the range must merely be “about” 30 to 2000 µm, which encompasses values on either side of the claimed range which do not fall within the claimed range. Appropriate clarification is required.
Claim 19 recites the phrase “to form the network, gelation system or scaffold for encapsulating and accommodating the target cell masses” in lines 2-4, which is indefinite. It is unclear by the recitation of “for encapsulating” whether or not the claim requires encapsulating the target cell masses or only requires inducing a formation of a network, gelation system or scaffold that may or may not encapsulate the target cell masses. Additionally, it is unclear what the term “accommodating” implies in relation to the target cell mass and the specification does not provide a definition for the term “accommodating”. Appropriate clarification is required.
Claim Rejections - 35 USC § 102
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 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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(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.
Claims 1-2, 4-8, and 23 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Zhao et al (US11994456B2).
Claim Interpretation: The “cell mass” of claim 1 is being interpreted to include single cells or cell cultures including cell clumps. Claim 9 contains the limitation “wherein the formulation of the biomaterial and the target cell masses are mixed in the compartment in a volume ratio of 1:1”, which has been rejected above under 112(b) for being indefinite. The limitation is being interpreted to be met by any ratio of mixing in the art.
With regards to claim 1, Zhao teaches a method for selecting cell masses from a source and fabricating a biomaterial-encapsulated cell mass model (BECM) based on the selected cell masses comprising: providing one or more cell masses in an intact or partially digested state (col. 9, para 2), subjecting the intact or partially digested cell masses to a cell imaging device (Claim 1 of Zhao), providing a formulation of a biomaterial to encapsulate the cell masses in-situ (Claim 1 of Zhao), acquiring images of the cell masses to target cell masses to be encapsulates into the biomaterial (Claim 1 of Zhao), determining location, dimension, cell number, cell phenotype and optical signal intensity of the target cell masses with respect to non-target cell masses in the images (Claim 1 of Zhao; Col. 10, para 3), and mixing the formulation of the biomaterial with the target cell masses in the corresponding compartment followed by inducing a formation of a network, gelation system or scaffold for encapsulating and accommodating the target cell masses (Claim 1 of Zhao). Zhao teaches that the cells of the invention can be primary cells or transformed cells as required by claim 2 (Col. 4, para 5). Zhao teaches that the biomaterial in which the cell masses are encapsulated in is biocompatible and that the gelation of the biomaterial is stimulated by light irradiation, which also constitutes a chemical composition change, as required by claim 4 (Col. 2, para 3). Zhao teaches wherein the precursor is a photo-crosslinkable hydrogel as required by claim 5 (Col. 4, para 6). Zhao teaches that the photo-crosslinkable hydrogel is Gel-MA™ as required by claim 6 (Col. 6, Para 12 (see line 40)). Zhao teaches that the composition also comprises a photo-initiator which is taught to be LAP as required by claims 7 and 8 (Col. 6, Para 12 (see line 40-41)). Zhao teaches that the cell masses are mixed with the biomaterial (Claims 1, 24, and 25 of Zhao). Zhao teaches the cell mass encapsulated material fabricated according to claim 1 as required by claim 23 (Col. 2, para 3).
Therefore, Zhao anticipates the claims.
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.
Claims 1, 3, 9, and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al (US11994456B2), in view of Moore et al (US20200386742A1).
Regarding claims 3, 9, and 16-17, the limitations of the independent claim 1 are taught by Zhao above.
Zhao does not teach that that the cell masses are spheroids and organoids as required by claim 3. Zhao does not teach that the formulation of the biomaterial and the target cell masses are mixed in the compartment in a volume ratio of 1:1 as required by claim 9. Zhao does not teach that the target cell masses have an average diameter from about 30 to 2000 µm as required by claim 16. Zhao does not teach that the target cell masses emit optical signals detectable by the cell imaging device representing expression of one or more biomarkers by one or more cell phenotypes of interest as required by claim 17.
However, Moore teaches a method of curing target cell masses which are spheroids and organoids ([0136] and claim 1 or Moore) in a hydrogel as required by claim 3. Moore discloses that the target cell masses have an average diameter between 30-2000 microns as required by claim 16 ([0008]/[0131]). Moore also discloses that the cell masses emit optical signals detectable by the cell imaging device representing expression of one or more biomarkers by one or more cell phenotypes of interest as required by claim 17 ([0187]). Additionally, Moore teaches “[u]sing a dual hydrogel construct and spheroids comprising neuronal cells, the present disclosure provides methods, devices, and systems for in vitro spatially-controlled, three-dimensional models that permit intra- and extra-cellular electro-physiological measurements and recordings” (abstract).
Moore teaches mixing hydrogel solutions in a 1:1 ratio and mixing cell/spheroids in a 1:1 cell ratio ([0280]/[0135]), which renders the claim limitation of “the biomaterial and the target cell masses are mixed in the compartment in a volume ratio of 1:1” unpatentable as required by claim 9. Mixing cells and solutions/biomaterials in a 1:1 ratio is a routine and obvious in the art of cell culture.
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method of separating cell particles prepared in a light-curable hydrogel taught by Zhao with the spheroid/organoid compositions in hydrogels taught by Moore to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Moore teaches “[u]sing a dual hydrogel construct and spheroids comprising neuronal cells, the present disclosure provides methods, devices, and systems for in vitro spatially-controlled, three-dimensional models that permit intra- and extra-cellular electro-physiological measurements and recordings” (abstract). One of ordinary skill in the art would have a reasonable expectation of success when combining Zhao with Moore because both are in the art of curing hydrogel compositions for controlling the movement or capture of specific cells and/or spheroid/organoids.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 1, 10, 13-15, 19-20, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al (US11994456B2), in view of Tafas et al (US20210252518A1).
With regards to claims 10, 13-15, 19-20, and 22, the limitations of the independent claim 1 are taught above by Zhao.
Zhao teaches that the cell imaging device comprises a microscope for acquiring visible light, fluorescent, and luminescent signals from the cell masses as required by claim 10 (See claims 1 and 14 of Zhao). Zhao teaches that the cell imaging device contains a camera for outputting images of the cell masses comprising bright-field, dark-field, fluorescent, and luminescent images as required by claim 10 (see claims 1 and 14 of Zhao). Zhao teaches that the method further comprises mapping the target cell madded determined on the images after mixing the cell masses with the biomaterial as required by claim 13 (see claim 1 of Zhao). Zhao teaches wherein the mapping of the target cell masses is performed by algorithm (Col. 12, second to last para) or manually as required by claim 14 (Col. 2, para 5). Zhao teaches that the image analysis algorithm is configured to differentiate between non target and target cell masses and is able to calculate the exact location of each cell mass relative to the others as required by claim 15 (Col. 13, para 1). Zhao teaches wherein a stimulation to induce the biomaterial which contains both a precursor and the photo-initiator, to form the network, gelation system, or scaffold is specifically applied to the compartments at where the target cell masses are mapped from the images as required by claims 19 and 20 (Col. 13, para 1, claim 1 of Zhao, and Fig. 1). Zhao teaches that the method further comprises sorting the BECM by a sorting mechanism using a light scattering device as required by claim 22 (Col. 2, para 3).
Zhao does not teach that the cell imaging device contains one or more compartments comprising a temperature control mechanism and a gas regulation mechanism as required by claim 10.
However, Tafas discloses a biological sample holder and handler system which is an automated microscope employed to image cells mixed in a hydrogel solution ([0012] and [0107]). Tafas discloses that the biological sample holder and handler system contains a microscope which has a specially designed chamber for gas regulation and control of temperature of the cell culture being observed as required by claim 10 ([0097]).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method of separating cell particles prepared in a light-curable hydrogel taught by Zhao with the microscope based system with gas and temperature regulation taught by Tafas to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Tafas teaches that the disclosed system allows for the observation and culture of cell under more realistic biological conditions ([0012]-[0013]). One of ordinary skill in the art would have a reasonable expectation of success when combining Zhao with Tafas because both concern cell microscopy and imaging.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 1 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al (US11994456B2), in view of Tafas et al (US20210252518A1), as applied to claims 1, 10, 13-15, 19-20, and 22 above, and in further view of Moore et al (US20200386742A1).
With regards to claim 18, the limitations of the independent claim 1 are taught above.
Zhao and Tefas do not teach that each of the target cell masses are non-target cell masses are separated by a distance larger than 0-2000 µm as required by claim 18.
However, Moore teaches a method of curing target cell masses which are spheroids and organoids ([0136] and claim 1 or Moore) in a hydrogel. Moore demonstrates that the desired cell masses are above 2000 µm apart as required by claim 18 ([0056] and Fig. 25).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method of separating cell particles prepared in a light-curable hydrogel taught by Zhao with the spheroid/organoid compositions in hydrogels taught by Moore to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Moore teaches “[u]sing a dual hydrogel construct and spheroids comprising neuronal cells, the present disclosure provides methods, devices, and systems for in vitro spatially-controlled, three-dimensional models that permit intra- and extra-cellular electro-physiological measurements and recordings” (abstract). One of ordinary skill in the art would have a reasonable expectation of success when combining Zhao with Moore because both are in the art of curing hydrogel compositions for controlling the movement or capture of specific cells and/or spheroid/organoids.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 1 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al (US11994456B2), in view of Wang et al (US20100178304A1).
With regards to claim 4, the limitations of the independent claim 1 are taught above by Zhao. Additionally, Zhao teaches the embodiments of claim 4 wherein the stimulation of the biomaterial is completed through light irradiation and chemical composition changes as described in the 102 rejection employing Zhao above.
Zhao does not teach the alternative embodiment of claim 4 wherein the biomaterial is stimulated by temperature change or pH change as required in the alternative by claim 4.
However, Wang teaches about conditions for gelation of various hydrogels, which can be used for the purpose of encapsulating biological materials and viable cells (abstract). Wang teaches that both changes in temperature and pH are physical stimulants which are commonly used for the gelation of various hydrogel compositions as required in the alternative by claim 4 ([0022]). Additionally, Wang teaches that “[t]he hydrogels resulting from the methods of the invention exhibit both good mechanical properties and proteolytic degradation profiles” ([0009]).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method of separating cell particles prepared in a light-curable hydrogel taught by Zhao with the gelation techniques taught by Wang to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Wang teaches that “[t]he hydrogels resulting from the methods of the invention exhibit both good mechanical properties and proteolytic degradation profiles” ([0009]). One of ordinary skill in the art would have a reasonable expectation of success when combining Zhao with Wang because both are in the art of curing hydrogel compositions for controlling the movement or capture of biological materials such as viable cells.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/DAVID A MONTANARI/Examiner, Art Unit 1632