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 .
Claims 1-20 are pending.
Specification
The title will have to be changed to more closely reflect the claimed subject matter.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Written Description
Claims 1-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
A) The specification lacks written description for any isolated glioblastoma model comprising a blood-brain barrier, a “neural compartment”, a “brain parenchyma” and a “tumor organoid” as required in claim 1 other than the products known in the art.
Claim 1 is drawn to an in vitro bioengineered three-dimensional glioblastoma model, the model comprising: a blood brain barrier, a neural compartment, a brain parenchyma, and a tumor organoid.
The blood brain barrier may be from any species, e.g. fish, reptiles, amphibian, bird, or mammal.
The “neural compartment” may be from any species, e.g. fish, reptiles, amphibian, bird, or mammal.
The “brain parenchyma” may be from any species, e.g. fish, reptiles, amphibian, bird, or mammal.
The “tumor organoid” may be from any species, e.g. fish, reptiles, amphibian, bird, or mammal.
The metes and bounds of “blood brain barrier” in an isolated bioengineered model cannot be determine. The claims encompass an isolated head that contains an intact blood-brain barrier. Neal (Stem Cell Reports, 2019, Vol. 12, pg 1380-1388), Lippmann (Scientific Reports, 2014, Vol. 4, pg 1-10), Erickson (Fluids and Barriers of the CNS, 2020, Vol. 17, No. 26, pg 1-16), Faley (Stem Cell Reports, 2019, Vol. 12, pg 474-487), Bhalerao (Fluids Barriers CNS, 2020, Vol. 17, No. 22, pg 1-20) taught differentiating iPS cells into “blood-brain barrier endothelial cells”, but the claims are not so limited. Beyond that, it is unclear what structures/functions are required to obtain a “blood brain barrier” in vitro.
The metes and bounds of a “neural compartment” in an isolated engineered model cannot be determined. The concept encompasses isolated neural cells, but it is unclear what is required beyond that to be considered a “neural compartment”. The neural cells could be the same as the “blood brain barrier” or “brain parenchyma” or different.
The metes and bounds of a “brain parenchyma” in an isolated engineered model cannot be determined. The concept encompasses isolated brain cells, e.g. grey matter or white matter, but it is unclear what is required beyond that to be considered a “brain parenchyma”. The neural cells of the “brain parenchyma” could be the same as the “blood brain barrier” or “neural compartment” or different.
The body of the claim encompasses using any “tumor organoid” but the preamble is limited to making a “glioblastoma model”. The specification does not teach using any tumor organoid to obtain a “glioblastoma model” other than glioblastoma cells.
Skardal (Biofabrication, 2020, pg 1-36) taught an “organs-on-chips” platform but did not teach the composition contained a blood-brain barrier, neural components, brain parenchyma or glioblastoma
Skardal (Biotechnol Bioeng, 2016, Vol. 113, No. 9, pg 2020-2032) taught “Metastasis-on-a-chip” for tumor modeling but did not teach the composition contained a blood-brain barrier, neural components, brain parenchyma or glioblastoma.
Skardal (Sci. Reports, 2017, Vol. 7, No. 8837, pg 1-16) taught “three-tissue organ-on-a-chip platform” but did not teach the composition contained a blood-brain barrier, neural components, brain parenchyma or glioblastoma.
Maloney (Micromachines, 2020, Vol. 11, No. 208, pg 1-7) taught 3D bioprinted glioblastoma organoids for screening chemotherapy.
Wang (Microfluidic blood-brain barrier model provides in vivo-like barrier properties for drug permeability screening. Biotechnol Bioeng, 2017, Vol. 114, pg 184-194) taught a blood brain barrier model but did not teach the composition contained neural components, brain parenchyma or glioblastoma.
Zhang (PNAS, 2017, E2293-E2302) taught an “organs-on-chips” platform, Mazzocchi (Appl Phys Rev 2019, Vol. 6, No. 1, pg 1-22) taught 3D bioprinting for screening drugs, Tang (Advanced Materials, 2020, pg 1-25) taught 3D bioprinting strategies for modeling glioblastoma and the blood-brain barrier, Nzou (Sci. Reports, 2018, Vol. 8, No. 7413, pg 1-10) taught a human cortex spheroid with a blood brain barrier, and Sivakumar (Frontiers in Bioengineering and Biotech., 2020, Vol. 8, pg 1-9) taught multi-cell type glioblastoma spheroids for screening drugs, but it is unclear how these teachings correlate to the structures of in vitro glioblastoma model in claim 1. It is particularly unclear when a “blood brain barrier”, “neural compartment” or “brain parenchyma” has been achieved in vitro because the references do not teach the structures/functions that must be achieved in order to qualify as each in vitro.
The specification lacks written description for any “tumor organoid comprising one or more of the cells are encapsulated in an extracellular matrix-based hydrogel, the hydrogel comprising: hyaluronic acid, collagen, or gelatin, wherein the hyaluronic acid, collagen, or gelatin are chemically modified to enable covalent crosslinking to one another to form a hydrogel, and wherein additional extracellular matrix proteins or polysaccharides are covalently bound to the hyaluronic acid, collagen, or gelatin” as required in claim 6. The metes and bounds of the concept cannot be determined from the specification or the art at the time of filing. The specification does not teach encapsulating any glioblastoma cells in any hyaluronic acid, collagen, or gelatin as claimed.
The specification lacks written description for any “blood brain barrier is evaluated by the presence of a tight junction biomarker or evidence of transport selectivity based on molecular weight of a substance” as required in claim 8. The metes and bounds of the concept cannot be determined from the specification or the art at the time of filing. The specification does not teach evaluating any blood brain barrier as claimed.
The specification lacks written description for any glioblastoma model comprising any “blood brain barrier”, “neural compartment”, “brain parenchyma”, and glioblastoma in a “microfluidic device” as required in claim 10. The metes and bounds of the concept cannot be determined from the specification or the art at the time of filing. The specification does not teach encapsulating any “blood brain barrier”, “neural compartment”, “brain parenchyma”, and glioblastoma in a “microfluidic device” as claimed.
The specification lacks written description for fluid flowing through the model in a microfluidic device “in parallel to the cells and blood brain barrier of the model” as required in claim 11. The metes and bounds of the concept cannot be determined from the specification or the art at the time of filing. The specification does not teach encapsulating any “blood brain barrier”, “neural compartment”, “brain parenchyma”, and glioblastoma in a “microfluidic device” and driving fluid through the model and “in parallel to the cells and blood brain barrier of the model” as claimed.
The specification lacks written description for fluid containing a drug, therapeutic, cell or compound that flows through the model in a microfluidic device as required in claim 12. The metes and bounds of the concept cannot be determined from the specification or the art at the time of filing. The specification does not teach encapsulating any “blood brain barrier”, “neural compartment”, “brain parenchyma”, and glioblastoma in a “microfluidic device” and driving fluid containing a drug, therapeutic, cell or compound through the model as claimed.
The specification lacks written description for any “microfluidic device” fabricated by soft lithography or layer of laser cut components or 3D printed as required in claim 13. The metes and bounds of the concept cannot be determined from the specification or the art at the time of filing. The structures/functions associated with “microfluidic device” fabricated by soft lithography or layer of laser cut components or 3D printed in claim 13 capable of containing a glioblastoma having the components of claim 1 cannot be determined.
Claim 14 lacks written description for reasons set forth above other than the methods described in the art. The specification does not teach how to measure any parameter in the model after administering a treatment or how to make any assessment about the effect of the treatment by any means other than those well-known in the art described above.
The specification lacks written description for any patient-specific model wherein the “tumor organoid [is] patient derived” and the “effectiveness of treatment for glioblastoma is specific for the patient” as required in claim 15. The tumor may be from a patient, but the specification does not teach how to make the evaluation specific for any patient.
Claims 16-20 lack written description for reasons set forth above other than the methods described in the art for reasons cited above.
Enablement
Claims 1-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for products known in the art does not enable making/using any in vitro 3D bioengineered model of glioblastoma as broadly encompassed by claim 1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make/use the invention commensurate in scope with these claims.
The specification does not enable making/using any model of claim 1 other than those known in the art.
Claim 1 is recited above.
The metes and bounds of “blood brain barrier” in an isolated bioengineered model cannot be determine. The claims encompass an isolated head that contains an intact blood-brain barrier. Neal (Stem Cell Reports, 2019, Vol. 12, pg 1380-1388), Lippmann (Scientific Reports, 2014, Vol. 4, pg 1-10), Erickson (Fluids and Barriers of the CNS, 2020, Vol. 17, No. 26, pg 1-16), Faley (Stem Cell Reports, 2019, Vol. 12, pg 474-487), Bhalerao (Fluids Barriers CNS, 2020, Vol. 17, No. 22, pg 1-20) taught differentiating iPS cells into “blood-brain barrier endothelial cells”, but the claims are not so limited. Beyond that, it is unclear what structures/functions are required to obtain a “blood brain barrier” in vitro.
The metes and bounds of a “neural compartment” in an isolated engineered model cannot be determined. The concept encompasses isolated neural cells, but it is unclear what is required beyond that to be considered a “neural compartment”. The neural cells could be the same as the “blood brain barrier” or “brain parenchyma” or different.
The metes and bounds of a “brain parenchyma” in an isolated engineered model cannot be determined. The concept encompasses isolated brain cells, e.g. grey matter or white matter, but it is unclear what is required beyond that to be considered a “brain parenchyma”. The neural cells of the “brain parenchyma” could be the same as the “blood brain barrier” or “neural compartment” or different.
The body of the claim encompasses using any “tumor organoid” but the preamble is limited to making a “glioblastoma model”. The specification does not teach using any tumor organoid to obtain a “glioblastoma model” other than glioblastoma cells.
Skardal (Biofabrication, 2020, pg 1-36) taught an “organs-on-chips” platform but did not teach the composition contained a blood-brain barrier, neural components, brain parenchyma or glioblastoma
Skardal (Biotechnol Bioeng, 2016, Vol. 113, No. 9, pg 2020-2032) taught “Metastasis-on-a-chip” for tumor modeling but did not teach the composition contained a blood-brain barrier, neural components, brain parenchyma or glioblastoma.
Skardal (Sci. Reports, 2017, Vol. 7, No. 8837, pg 1-16) taught “three-tissue organ-on-a-chip platform” but did not teach the composition contained a blood-brain barrier, neural components, brain parenchyma or glioblastoma.
Maloney (Micromachines, 2020, Vol. 11, No. 208, pg 1-7) taught 3D bioprinted glioblastoma organoids for screening chemotherapy.
Wang (Microfluidic blood-brain barrier model provides in vivo-like barrier properties for drug permeability screening. Biotechnol Bioeng, 2017, Vol. 114, pg 184-194) did not teach the composition contained neural components, brain parenchyma or glioblastoma.
Mazzocchi (Appl Phys Rev 2019, Vol. 6, No. 1, pg 1-22) taught 3D bioprinting for screening drugs, Tang (Advanced Materials, 2020, pg 1-25) taught 3D bioprinting strategies for modeling glioblastoma and the blood-brain barrier, Nzou (Sci. Reports, 2018, Vol. 8, No. 7413, pg 1-10) taught a human cortex spheroid with a blood brain barrier, and Sivakumar (Frontiers in Bioengineering and Biotech., 2020, Vol. 8, pg 1-9) taught multi-cell type glioblastoma spheroids for screening drugs, but it is unclear how these teachings correlate to the structures of in vitro glioblastoma model in claim 1. It is particularly unclear when a “blood brain barrier”, “neural compartment” or “brain parenchyma” has been achieved in vitro because the references do not teach the structures/functions that must be achieved in order to qualify as each in vitro.
The specification does not enable making any “tumor organoid comprising one or more of the cells are encapsulated in an extracellular matrix-based hydrogel, the hydrogel comprising: hyaluronic acid, collagen, or gelatin, wherein the hyaluronic acid, collagen, or gelatin are chemically modified to enable covalent crosslinking to one another to form a hydrogel, and wherein additional extracellular matrix proteins or polysaccharides are covalently bound to the hyaluronic acid, collagen, or gelatin” as required in claim 6. The metes and bounds of the concept cannot be determined from the specification or the art at the time of filing. The specification does not teach encapsulating any glioblastoma cells in any hyaluronic acid, collagen, or gelatin as claimed.
The specification does not enable making any “blood brain barrier is evaluated by the presence of a tight junction biomarker or evidence of transport selectivity based on molecular weight of a substance” as required in claim 8. The metes and bounds of the concept cannot be determined from the specification or the art at the time of filing. The specification does not teach evaluating any blood brain barrier as claimed.
The specification does not enable making any glioblastoma model comprising any “blood brain barrier”, “neural compartment”, “brain parenchyma”, and glioblastoma in a “microfluidic device” as required in claim 10. The metes and bounds of the concept cannot be determined from the specification or the art at the time of filing. The specification does not teach encapsulating any “blood brain barrier”, “neural compartment”, “brain parenchyma”, and glioblastoma in a “microfluidic device” as claimed.
The specification does not enable fluid flowing through the model in a microfluidic device “in parallel to the cells and blood brain barrier of the model” as required in claim 11. The metes and bounds of the concept cannot be determined from the specification or the art at the time of filing. The specification does not teach encapsulating any “blood brain barrier”, “neural compartment”, “brain parenchyma”, and glioblastoma in a “microfluidic device” and driving fluid through the model and “in parallel to the cells and blood brain barrier of the model” as claimed.
The specification does not enable fluid containing a drug, therapeutic, cell or compound that flows through the model in a microfluidic device as required in claim 12. The metes and bounds of the concept cannot be determined from the specification or the art at the time of filing. The specification does not teach encapsulating any “blood brain barrier”, “neural compartment”, “brain parenchyma”, and glioblastoma in a “microfluidic device” and driving fluid containing a drug, therapeutic, cell or compound through the model as claimed.
The specification does not enable making any “microfluidic device” fabricated by soft lithography or layer of laser cut components or 3D printed as required in claim 13. The metes and bounds of the concept cannot be determined from the specification or the art at the time of filing. The structures/functions associated with “microfluidic device” fabricated by soft lithography or layer of laser cut components or 3D printed in claim 13 capable of containing a glioblastoma having the components of claim 1 cannot be determined.
Claim 14 is not enabled for reasons set forth above other than the methods described in the art. The specification does not teach how to measure any parameter in the model after administering a treatment or how to make any assessment about the effect of the treatment by any means other than those well-known in the art described above.
The specification does not enable making for any patient-specific model wherein the “tumor organoid [is] patient derived” and the “effectiveness of treatment for glioblastoma is specific for the patient” as required in claim 15. The tumor may be from a patient, but the specification does not teach how to make the evaluation specific for any patient.
Claims 16-20 are not enabled for reasons set forth above other than the methods described in the art for reasons cited above.
Indefiniteness
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.
The metes and bounds of “blood brain barrier” in an isolated bioengineered model in claim 1 cannot be determine. The claims encompass an isolated head that contains an intact blood-brain barrier. Neal (Stem Cell Reports, 2019, Vol. 12, pg 1380-1388), Lippmann (Scientific Reports, 2014, Vol. 4, pg 1-10), Erickson (Fluids and Barriers of the CNS, 2020, Vol. 17, No. 26, pg 1-16), Faley (Stem Cell Reports, 2019, Vol. 12, pg 474-487), Bhalerao (Fluids Barriers CNS, 2020, Vol. 17, No. 22, pg 1-20) taught differentiating iPS cells into “blood-brain barrier endothelial cells”, but the claims are not so limited. Beyond that, it is unclear what structures/functions are required to obtain a “blood brain barrier” in vitro.
The metes and bounds of a “neural compartment” in an isolated engineered model in claim 1 cannot be determined. The concept encompasses isolated neural cells, but it is unclear what is required beyond that to be considered a “neural compartment”. The neural cells could be the same as the “blood brain barrier” or “brain parenchyma” or different.
The metes and bounds of a “brain parenchyma” in an isolated engineered model in claim 1 cannot be determined. The concept encompasses isolated brain cells, e.g. grey matter or white matter, but it is unclear what is required beyond that to be considered a “brain parenchyma”. The neural cells of the “brain parenchyma” could be the same as the “blood brain barrier” or “neural compartment” or different.
The body of claim 1 encompasses using any “tumor organoid” but the preamble is limited to making a “glioblastoma model”. The specification does not teach using any tumor organoid to obtain a “glioblastoma model” other than glioblastoma cells.
Skardal (Biofabrication, 2020, pg 1-36), Zhang (PNAS, 2017, E2293-E2302) taught an “organs-on-chips” platform, Mazzocchi (Appl Phys Rev 2019, Vol. 6, No. 1, pg 1-22) taught 3D bioprinting for screening drugs, Tang (Advanced Materials, 2020, pg 1-25) taught 3D bioprinting strategies for modeling glioblastoma and the blood-brain barrier, Nzou (Sci. Reports, 2018, Vol. 8, No. 7413, pg 1-10) taught a human cortex spheroid with a blood brain barrier, Skardal (Biotechnol Bioeng, 2016, Vol. 113, No. 9, pg 2020-2032) taught “Metastasis-on-a-chip” for tumor modeling, Skardal (Sci. Reports, 2017, Vol. 7, No. 8837, pg 1-16) taught “three-tissue organ-on-a-chip platform”, and Sivakumar (Frontiers in Bioengineering and Biotech., 2020, Vol. 8, pg 1-9) taught multi-cell type glioblastoma spheroids for screening drugs, but it is unclear how these teachings correlate to the structures of in vitro glioblastoma model in claim 1. It is particularly unclear when a “blood brain barrier”, “neural compartment” or “brain parenchyma” has been achieved in vitro because the references do not teach the structures/functions that must be achieved in order to qualify as each in vitro.
The metes and bounds of a “tumor organoid comprising one or more of the cells are encapsulated in an extracellular matrix-based hydrogel, the hydrogel comprising: hyaluronic acid, collagen, or gelatin, wherein the hyaluronic acid, collagen, or gelatin are chemically modified to enable covalent crosslinking to one another to form a hydrogel, and wherein additional extracellular matrix proteins or polysaccharides are covalently bound to the hyaluronic acid, collagen, or gelatin” in claim 6 cannot be determined. The metes and bounds of the concept cannot be determined from the specification or the art at the time of filing. The specification does not teach encapsulating any glioblastoma cells in any hyaluronic acid, collagen, or gelatin as claimed. Accordingly, those of skill would not be able to determine the structures/functions associated with the phrase in claim 6.
The metes and bounds of a model in which the “blood brain barrier is evaluated by the presence of a tight junction biomarker or evidence of transport selectivity based on molecular weight of a substance” in claim 8 cannot be determined. The metes and bounds of the concept cannot be determined from the specification or the art at the time of filing. The specification does not teach evaluating any blood brain barrier as claimed. Accordingly, those of skill would not be able to determine the structures/functions of the “model” that are associated with the evaluation in claim 8.
The metes and bounds of a glioblastoma model comprising any “blood brain barrier”, “neural compartment”, “brain parenchyma”, and glioblastoma in a “microfluidic device” in claim 10 cannot be determined. The metes and bounds of the concept cannot be determined from the specification or the art at the time of filing. The specification does not teach encapsulating any “blood brain barrier”, “neural compartment”, “brain parenchyma”, and glioblastoma in a “microfluidic device” as claimed. Accordingly, those of skill would not be able to determine when the “model” was in a “microfluidic” device.
The metes and bounds of a “microfluidic” device with fluid flowing through the model in a microfluidic device “in parallel to the cells and blood brain barrier of the model” in claim 11 cannot be determined. The metes and bounds of the concept cannot be determined from the specification or the art at the time of filing. The specification does not teach encapsulating any “blood brain barrier”, “neural compartment”, “brain parenchyma”, and glioblastoma in a “microfluidic device” and driving fluid through the model and “in parallel to the cells and blood brain barrier of the model” as claimed.
The phrase “the microfluidic device in claim 11 lacks antecedent basis in claim 11.
The metes and bounds of a model with fluid containing a drug, therapeutic, cell or compound that flows through the model in a microfluidic device in claim 12 cannot be determined. The metes and bounds of the concept cannot be determined from the specification or the art at the time of filing. The specification does not teach encapsulating any “blood brain barrier”, “neural compartment”, “brain parenchyma”, and glioblastoma in a “microfluidic device” and driving fluid containing a drug, therapeutic, cell or compound through the model as claimed. Accordingly, those of skill would not be able to determine when the “model” met the limitations claimed.
The metes and bounds of a “microfluidic device” fabricated by soft lithography or layer of laser cut components or 3D printed in claim 13 cannot be determined. The metes and bounds of the concept cannot be determined from the specification or the art at the time of filing. The structures/functions associated with “microfluidic device” fabricated by soft lithography or layer of laser cut components or 3D printed in claim 13 capable of containing a glioblastoma having the components of claim 1 cannot be determined. Accordingly, those of skill would not be able to determine when the “model” met the limitations claimed.
Claim 14 is indefinite for reasons set forth above.
The metes and bounds of a patient-specific model wherein the “tumor organoid [is] patient derived” and the “effectiveness of treatment for glioblastoma is specific for the patient” in claim 15 cannot be determined. The tumor may be from a patient, but the specification does not teach how to make the evaluation specific for any patient. Accordingly, those of skill would not be able to determine when the “model” met the limitations claimed.
Claims 16-20 are indefinite for reasons set forth above.
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.
Claims 1-6, 8-18, 20 are rejected under 35 U.S.C. 102a1 as being anticipated by Griffin (Neuro-Oncology Advances, 2022, Vol. 4, No. 1, pg 1-13, available Nov. 18, 2021).
Griffin taught postmortem brain donations with glioblastoma for research (pg 2). They inherently MUST contain tissue of the blood brain barrier, neural compartments, brain parenchymal tissue, and glioblastoma because they are entire brains that have been isolated. They are “bioengineered” because they have been manipulated by the hand of man and used for research. They are 3D. This is all that is required to meet the limitations of claim 1.
Any of the tissues can be considered a “extracellular matrix of hydrogel” as required in claim 2 because they are matrix of polymer chains that absorb fluid.
The container is an “implantable device” as required in claim 3 because it can be used to release treatments or adjuvant to the glioblastoma.
The glioblastoma is “derived” from a “tumor biospecimen” as required in claim 4.
The glioblastoma contains glioblastoma cells as required in claim 5.
The brain tissue comprises collagen that is “covalently crosslinked” and bound to other proteins or polysaccharides as required in claim 6.
Claim 8 has been included because the evaluation in claim 8 bears no patentable weight in distinguishing the structures/functions of the brain tissue of Griffin from the glioblastoma model claimed.
Claim 9 has been included because the “cells are not subject to cellular passage”.
Claim 10 has been included because the metes and bounds of a “microfluidic device” cannot be determined.
Claims 11-13 have been included because they do not further limit the structure/function of the model.
Claim 14 has been included because Griffin taught administering compounds to the brain tissue.
Claim 15 has been included because Griffin taught the brain tissue was “specific” to a specific person.
Claims 16-18, 20 have been included for reasons set forth above.
Claims 1-6, 8-18, 20 are rejected under 35 U.S.C. 103 as being unpatentable over Skardal (20190345439).
Skardal taught 3D bioengineered glioblastoma and astrocytes in a hydrogel (Fig. 18; para 43; pg 6, para 66; pg 9, para 98; pg 11, para 113, 114; para 154, 169, 190, 191, 192). The astrocytes are the blood brain barrier, brain parenchyma, and neural compartment in claims 1 and 16 because the metes and bounds of each are unclear. The glioblastoma are the tumor organoid in claim 1.
Skardal used hydrogel as required in claim 2 (throughout).
Skardal taught using a device to deliver a compound which is equivalent to claim 3 (para 117, et al).
The glioblastoma is from a patient as required in claim 4 (para 43, 63, 64, et al).
Skardal used astrocytes as required in claim 5.
Skardal used hyaluronic acid, collagen, or gelatin as required in claim 6 (para 4, 26, 27, 28, 53, et al.).
Claim 8 has been included because the evaluation in claim 8 bears no patentable weight in distinguishing the structures/functions of the brain tissue of Skardal from the glioblastoma model claimed.
Claim 9 has been included because the “cells are not subject to cellular passage”.
Claim 10 has been included because Skardal taught a “microfluidic device” (para 37, 39, 43, et al).
Claims 11-13 have been included because they do not further limit the structure/function of the model.
Claim 14 has been included because Skardal taught administering compounds to the model.
Claim 15 has been included because Skardal taught the brain tissue was “specific” to a specific person.
Claims 16-18, 20 have been included for reasons set forth above.
Claims 1-6, 8-18, 20 are rejected under 35 U.S.C. 103 as being unpatentable over Tang (Advanced Materials, Feb 2, 2021, Vol. 33, No. 5, pg 1-25).
Tang taught a 3D bioengineered model of glioblastoma and blood brain barrier tissue (Title, Materials and Methods). The blood brain barrier tissue of Tang is the blood brain barrier, brain parenchyma, and neural compartment in claims 1 and 16 because the metes and bounds of each are unclear. The glioblastoma of Tang are the tumor organoid in claim 1.
Tang used hydrogel as required in claim 2 (pg 2, col. 2, 1st para).
Tang taught using a device to deliver drugs which is equivalent to claim 3 (pg 2, line 1; pg 2, col. 1, 1st full para, et al.).
The glioblastoma is from a patient as required in claim 4 (pg 11, 4.1.4).
Tang used neurons as required in claim 5 (throughout).
Tang used collagen as required in claim 6 (pg 16, col. 2, line 6).
Claim 8 has been included because the evaluation in claim 8 bears no patentable weight in distinguishing the structures/functions of the brain tissue of Tang from the glioblastoma model claimed.
Claim 9 has been included because the “cells are not subject to cellular passage”.
Claim 10 has been included because Tang taught a “microfluidic device” (pg 16, col. 2, last full para).
Claims 11-13 have been included because they do not further limit the structure/function of the model.
Claim 14 has been included because Tang taught administering compounds to the model.
Claim 15 has been included because Tang taught the brain tissue was “specific” to a specific person.
Claims 16-18, 20 have been included for reasons set forth above.
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.
Claims 7, 19 are rejected under 35 U.S.C. 103 as being unpatentable over Griffin (Neuro-Oncology Advances, 2022, Vol. 4, No. 1, pg 1-13, available Nov. 18, 2021), Skardal (20190345439), or Tang (Advanced Materials, Feb 2, 2021, Vol. 33, No. 5, pg 1-25) in view of Burdick (Biomaterials, 2002, Vol. 23, pg 4315-4323).
Griffin, Skardal, or Tang taught a model of glioblastoma for reasons cited above. Griffin, Skardal, or Tang did not teach the model comprised RGD (SEQ ID NO: 1) as required in claims 7 and 19.
However, adding RGD to compounds for tissue engineering was well-known as described by Burdick (abstract; methods).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make a model of glioblastoma as described by Griffin, Skardal, or Tang using RGD described by Burdick. Those of ordinary skill in the art at the time of filing would have been motivated to improve cell adhesion.
Thus, Applicants' claimed invention as a whole is prima facie obvious in the absence of evidence to the contrary.
Claims 1-6, 8-18, 20 are rejected under 35 U.S.C. 103 as being unpatentable over Skardal (20190345439) in view of Tang (Advanced Materials, Feb 2, 2021, Vol. 33, No. 5, pg 1-25).
Skardal taught 3D bioengineered glioblastoma and astrocytes in a hydrogel (Fig. 18; para 43; pg 6, para 66; pg 9, para 98; pg 11, para 113, 114; para 154, 169, 190, 191, 192). The astrocytes are the blood brain barrier, brain parenchyma, and neural compartment in claims 1 and 16 because the metes and bounds of each are unclear. The glioblastoma are the tumor organoid in claim 1.
Tang taught a 3D bioengineered model of glioblastoma and blood brain barrier tissue (Title, Materials and Methods). The blood brain barrier tissue of Tang is the blood brain barrier, brain parenchyma, and neural compartment in claims 1 and 16 because the metes and bounds of each are unclear. The glioblastoma of Tang are the tumor organoid in claim 1.
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make the glioblastoma/astrocyte model of Skardal and add the blood brain barrier and brain parenchyma of Tang. Those of ordinary skill in the art at the time of filing would have been motivated to do so to more accurately mimic glioblastoma.
Claims 2-6, 8-18, 20 have been included for reasons set forth above.
Claims 7 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Skardal (20190345439) in view of Tang (Advanced Materials, Feb 2, 2021, Vol. 33, No. 5, pg 1-25) as applied to claims 1-6, 8-18, 20 in view of Burdick (Biomaterials, 2002, Vol. 23, pg 4315-4323).
The combined teachings of Skardal and Tang taught a model of glioblastoma for reasons cited above. The combined teachings of Skardal and Tang did not teach the model comprised RGD (SEQ ID NO: 1) as required in claims 7 and 19.
However, adding RGD to compounds for tissue engineering was well-known as described by Burdick (abstract; methods).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make a model of glioblastoma as described by Skardal and Tang using RGD described by Burdick. Those of ordinary skill in the art at the time of filing would have been motivated to improve cell adhesion.
Thus, Applicants' claimed invention as a whole is prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638
Prosecution Insights