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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-11, 16, and 18, in the reply filed on 06/29/2026 is acknowledged.
Claims 48, 53-55, 57, and 61-62 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/29/2026.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/17/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 1 is objected to because of the following informalities:
In claim 1, please change the recitations of “tissue specific” to “tissue-specific” for consistency with the prior lines of the claim.
In claim 1, it is believed line 7 should end with a comma.
Appropriate correction is required.
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)(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 1-3, 10, and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by O’Neill et al. (WO 2017136786 A1) (already of record).
Regarding claim 1, O’Neill et al. discloses a cell culture platform (Abstract, para. 117) comprising:
one or more cell culture vessels comprising a plurality of compartments (para. 117) (Fig. 11A, sheet 12 of 28), each compartment housing a substrate adapted for culturing cells thereon (para. 117) (Fig. 11A, sheet 12 of 28), wherein each substrate comprises a decellularized tissue-specific extracellular matrix (ECM) derived from tissue of a different anatomical region (para. 6, 117),
wherein each tissue-specific ECM comprises a homogenous mixture of macromolecule fragments including collagen, elastin, and glycosaminoglycan (para. 105, 121) (Figs. 13A-13C, sheet 14 of 28),
wherein each tissue-specific ECM is obtained by a process comprising:
decellularizing a tissue to yield a decellularized ECM (para. 72-73),
freezing, pulverizing, and lyophilizing the decellularized ECM to obtain an ECM powder (para. 73), and
digesting the ECM powder with pepsin and hydrochloric acid to obtain the tissue-specific ECM (para. 73).
As to the limitation that the claimed platform is for modeling metastatic cancer, it is noted that statements in the preamble reciting the purpose or intended use of the claimed invention are evaluated to determine whether the recited purpose or intended use results in a structural difference, or in the case of process claims, manipulative difference, between the claimed invention and the prior art; moreover, if a prior art structure is capable of performing the intended use as recited in the preamble then it meets the claim (MPEP §2111.02). In this case, the preamble limitation does not introduce a structural difference and the prior art platform is fully capable of modeling metastatic cancer (e.g., a user could introduce tumor cells into each compartment as each compartment is fully capable of receiving such cells, see para. 117). Therefore, the limitation does not introduce a patentable distinction over the prior art.
Regarding claim 2, O’Neill et al. discloses wherein the tissue-specific ECM is kidney-specific ECM (para. 6, 117).
Regarding claim 3, O’Neill et al. discloses wherein the plurality of compartments of the one or more cell culture vessels comprise a first compartment housing a first substrate (cortex ECM), a second compartment housing a second substrate (medulla ECM), and a third compartment housing a third substrate (papilla ECM) (para. 117) (Figs. 11A-11B, sheet 12 of 28).
Regarding claim 10, O’Neill et al. discloses wherein each tissue-specific ECM is derived from healthy (non-metastatic) tissue (para. 57).
Regarding claim 18, O’Neill et al. discloses wherein each substrate is a media supplement (para. 175).
Claim Rejections - 35 USC § 102/103
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.
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, 10, 16, and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Skardal et al. (Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform), or alternatively, under 35 U.S.C. 103 as being unpatentable over Skardal et al. (Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform) in view of Skardal et al. (Tissue specific synthetic ECM hydrogels for 3-D in vitro maintenance of hepatocyte function) (hereinafter referred to by the reference title).
Regarding claim 1, Skardal et al. discloses a cell culture platform (Title, p. 2 last paragraph, p. 11 last 4 paragraphs) for modeling metastatic cancer (p. 2 3rd paragraph; the platform is structurally capable of modeling metastatic cancer as it is capable of hosting metastasizing cells therein, see entire document) comprising:
one or more cell culture vessels comprising a plurality of compartments (p. 2 last paragraph) (Fig. 1, p. 3), each compartment housing a substrate adapted for culturing cells thereon (p. 2 last paragraph) (Fig. 1, p. 3), wherein each substrate comprises a decellularized tissue-specific extracellular matrix (ECM) derived from tissue of a different anatomical region (liver-specific ECM and lung-specific ECM) (p. 2 last paragraph, p. 11 last paragraph-p. 12 2nd paragraph) (Fig. 1, p. 3),
wherein each tissue-specific ECM comprises a homogenous mixture of macromolecule fragments including collagen, elastin, and glycosaminoglycan (Skardal et al. explicitly discloses that the liver-specific ECM comprises this feature, see p. 12 2nd paragraph, and it is understood that the lung-specific ECM also comprises this feature as will be discussed in greater detail below),
wherein each tissue specific ECM is obtained by a process comprising:
decellularizing a tissue to yield a decellularized ECM (p. 11 last paragraph-p. 12 2nd paragraph).
As to the limitation of wherein each tissue-specific ECM comprises a homogenous mixture of macromolecule fragments including collagen, elastin, and glycosaminoglycan, Skardal et al. explicitly discloses this for the liver-specific ECM but does not explicitly disclose this for the lung-specific ECM. Nonetheless, the skilled artisan would understand from the disclosure of Skardal et al. as a whole that the disclosed lung-specific ECM necessarily comprises this feature, even if it is not explicitly disclosed. The skilled artisan would understand that native lung ECM inherently comprises collagen, elastin, and glycosaminoglycan, and obtaining decellularized lung ECM from native lung tissue as Skardal et al. describes (p. 11 last paragraph) would yield decellularized lung ECM that also comprises collagen, elastin, and glycosaminoglycan, especially as Skardal et al. is devoid of mention of removing such components. Specifically, Skardal et al. discloses that the lung tissue is decellularized “as has been described previously” (p. 11 last paragraph) in reference number 36 of their citations, which is the document titled “Tissue specific synthetic ECM hydrogels for 3-D in vitro maintenance of hepatocyte function” (see item 36 of the References, p. 15). “Tissue specific synthetic ECM hydrogels for 3-D in vitro maintenance of hepatocyte function” discloses obtaining tissue-specific ECM through a process comprising decellularizing a tissue to yield a decellularized ECM (p. 4566 1st column last paragraph-2nd column first paragraph), freezing, pulverizing, and lyophilizing the decellularized ECM to obtain an ECM powder (p. 4566 2nd column 2nd paragraph), and digesting the ECM powder with pepsin and hydrochloric acid to obtain the tissue-specific ECM (p. 4566 2nd column 2nd paragraph). This process preserves collagen, elastin, and glycosaminoglycan present in the native tissue such that they are still present in the tissue-specific ECM (Abstract, p. 4567) (Fig. 1, p. 4568). Therefore, the lung-specific ECM disclosed by Skardal et al. is obtained through a process that preserves collagen, elastin, and glycosaminoglycan.
Should it be found that the disclosure of Skardal et al. is not sufficient to anticipate the feature of wherein each tissue-specific ECM comprises a homogenous mixture of collagen, elastin, and glycosaminoglycan, then this subject matter nonetheless would have been obvious in view of the “Tissue specific synthetic ECM hydrogels for 3-D in vitro maintenance of hepatocyte function” reference. “Tissue specific synthetic ECM hydrogels for 3-D in vitro maintenance of hepatocyte function” discloses that the structural components of ECM including collagen, elastin, and glycosaminoglycan improve bioactivity of materials (p. 4566 1st column 2nd paragraph) and discloses a method of obtaining ECM that preserves these components, as discussed above. Therefore, it would have been obvious to one of ordinary skill in the art to modify the platform disclosed by Skardal et al. such that each tissue-specific ECM comprises a homogenous mixture of collagen, elastin, and glycosaminoglycan in order to arrive at tissue-specific ECM components that closely model in vivo conditions comprise sufficient bioactivity, thereby improving the experimental utility of the platform.
As to the limitation of wherein each tissue-specific ECM is obtained by a process comprising freezing, pulverizing, and lyophilizing the decellularized ECM to obtain an ECM powder, and digesting the ECM powder with pepsin and hydrochloric acid to obtain the tissue-specific ECM, Skardal et al. discloses that each tissue-specific ECM is obtained by a process as “described previously” (p. 11 last paragraph-p. 12 2nd paragraph) in reference number 36 of their citations, which is the document titled “Tissue specific synthetic ECM hydrogels for 3-D in vitro maintenance of hepatocyte function” (see item 36 of the References, p. 15). As discussed above, the process of this reference comprises freezing, pulverizing, and lyophilizing the decellularized ECM to obtain an ECM powder, and digesting the ECM powder with pepsin and hydrochloric acid to obtain the tissue-specific ECM. Therefore, it is understood that each tissue-specific ECM of the platform disclosed by Skardal et al. is in fact obtained by a process comprising freezing, pulverizing, and lyophilizing the decellularized ECM to obtain an ECM powder, and digesting the ECM powder with pepsin and hydrochloric acid to obtain the tissue-specific ECM.
Should it be found that the disclosure of Skardal et al. is not sufficient to anticipate the feature of freezing, pulverizing, and lyophilizing the decellularized ECM to obtain an ECM powder, and digesting the ECM powder with pepsin and hydrochloric acid to obtain the tissue-specific ECM, then this subject matter nonetheless would have been obvious in view of the “Tissue specific synthetic ECM hydrogels for 3-D in vitro maintenance of hepatocyte function” reference. The reference discloses obtaining a tissue-specific ECM according to such a process, wherein the tissue-specific ECM retains ECM components necessary for bioactivity, as discussed above. Therefore, it would have been obvious to one of ordinary skill in the art to modify the platform disclosed by Skardal et al. such that each tissue-specific ECM is obtained through a process recognized in the art to retain ECM components necessary for bioactivity, in order to arrive at tissue-specific ECM components that closely model in vivo conditions comprise sufficient bioactivity, thereby improving the experimental utility of the platform.
Regarding claim 2, Skardal et al. discloses wherein the tissue-specific ECM is liver-specific ECM and lung-specific ECM, as set forth above.
Regarding claim 3, Skardal et al. discloses wherein the plurality of compartments of the one or more cell culture vessels comprise a first compartment housing a first substrate, a compartment housing a second substrate, and a third compartment housing a third substrate (p. 2 last paragraph) (Fig. 1, p. 3).
Regarding claim 10, it is understood that Skardal et al. discloses wherein each tissue-specific ECM is derived from non-metastatic tissue as Skardal et al. is devoid of mention of the native tissue being metastatic (see p. 11 last paragraph-p. 12 second paragraph).
In any case, it would have been obvious to one of ordinary skill in the art at the time before the filing date of the claimed invention to derive each tissue-specific ECM from non-metastatic tissue, as Skardal et al. envisions using the platform to investigate tumor cell metastasis into tissue (p. 2 third paragraph), and the skilled artisan would have recognized the advantage of using healthy (non-metastatic) tissue-specific ECM to accurately model tumor metastasis into healthy tissue.
Regarding claim 16, Skardal et al. discloses wherein:
the one or more cell culture vessels comprise at least one microfluidic chip (p. 2 last paragraph) (Fig. 1, p. 2),
the plurality of compartments comprise a plurality of microfluidic chambers on the at least one microfluidic chip (p. 2 last paragraph) (Fig. 1, p. 2), and
the at least one microfluidic chip comprises one or more microfluidic channels fluidly communicating with the plurality of microfluidic chambers (p. 2 last paragraph) (Fig. 1, p. 2).
Regarding claim 18, Skardal et al. discloses wherein each substrate is a surface coating (p. 11 last paragraph) or a printable bioink (p. 12 second paragraph).
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 4 is rejected under 35 U.S.C. 103 as being unpatentable over Skardal et al. (Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform), or alternatively, under 35 U.S.C. 103 as being unpatentable over Skardal et al. (Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform) in view of Skardal et al. (Tissue specific synthetic ECM hydrogels for 3-D in vitro maintenance of hepatocyte function), as applied to claim 3, and in further view of Narkhede et al. (Biomimetic strategies to recapitulate organ specific microenvironments for studying breast cancer metastasis).
Regarding claim 4, Skardal et al. discloses the first, second, and third substrates, as set forth above, wherein the second substrate comprises lung-specific ECM derived from lung tissue (p. 2 last paragraph, p. 11 last paragraph) (Fig. 1, p. 3), and the third substrate comprises liver-specific ECM derived from liver tissue (p. 2 last paragraph, p. 12 2nd paragraph) (Fig. 1, p. 3).
Skardal et al. is silent as to wherein the first substrate comprises bone-specific ECM derived from bone tissue.
However, Skardal et al. envisions using the platform to investigate cancer metastasis (p. 2 3rd paragraph).
Narkhede et al. discloses that breast cancer related mortality is primarily related to metastasis to other organs, and that breast cancer commonly metastasizes to lung, liver, and bone (Abstract, p. 1091 column 1), and furthermore “Bone is one of the most preferred sites for breast cancer metastasis” (p. 1092 column 2 3rd paragraph). Narkhede et al. discloses that it was known in the art to recapitulate the bone ECM environment to study breast cancer metastasis experimentally (p. 1092 column 2 3rd paragraph).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the platform disclosed by Skardal et al. such that the first substrate comprises bone-specific ECM derived from bone tissue, as Skardal et al. discloses using tissue-specific ECM derived from tissue and Narkhede et al. further discloses using bone ECM as a highly experimentally relevant material for metastasis studies, and the skilled artisan would have been motivated to use a substrate recognized in the art to be highly relevant for metastasis of breast cancer to enhance the experimental utility of the platform as a model for breast cancer.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Skardal et al. (Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform), or alternatively, under 35 U.S.C. 103 as being unpatentable over Skardal et al. (Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform) in view of Skardal et al. (Tissue specific synthetic ECM hydrogels for 3-D in vitro maintenance of hepatocyte function), and in further view of Narkhede et al. (Biomimetic strategies to recapitulate organ specific microenvironments for studying breast cancer metastasis), as applied to claim 4, above, and in further view of Kolb et al. (The Bone Extracellular Matrix as an Ideal Milieu for Cancer Cell Metastases) and Daamen et al. (Preparation and evaluation of molecularly-defined collagen–elastin glycosaminoglycan scaffolds for tissue engineering).
Regarding claim 5, Skardal et al. in view of Narkhede et al. teaches wherein the first substrate comprises bone-specific ECM derived from bone tissue, as set forth above.
The prior art combination is silent as to wherein the first substrate comprises collagen in a concentration of about 580 to about 620 µg/mL, elastin in a concentration of about 40 µg /mL to about 50 µg /mL, and glycosaminoglycan in a concentration of about 10 µg /mL to about 20 µg /mL.
Kolb et al. discloses wherein native bone ECM comprises about 90% collagen (p. 6 last paragraph) and further comprises non-collagenous proteins including glycosaminoglycans (p. 8). Kolb et al. further discloses that bone ECM has a degree of elasticity (p. 2 last paragraph, p. 15 last paragraph).
Daamen et al. discloses an ECM for use in cell culture, comprising collagen, elastin, and glycosaminoglycan (Abstract), wherein the ECM can comprise various ratios of collagen to elastin (Abstract). Increasing elastin increases elasticity (Abstract), but an extremely high elastin content makes the ECM difficult to handle (p. 4008 entire page).
It has been held that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation, when the particular parameter is recognized as a result-effective variable (MPEP §2144.05). The prior art discloses general conditions for a concentration of collagen, elastin, and glycosaminoglycan in the context of bone ECM, and one of ordinary skill in the art would recognize the amounts thereof to be a result-effective variable based on the teachings of the prior art, as discussed above. Therefore, it would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to discover through routine experimentation an optimum or workable range for the concentration of each of collagen, elastin, and glycosaminoglycan of the first substrate, in order to arrive at a bone-specific substrate having desired properties.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Skardal et al. (Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform), or alternatively, under 35 U.S.C. 103 as being unpatentable over Skardal et al. (Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform) in view of Skardal et al. (Tissue specific synthetic ECM hydrogels for 3-D in vitro maintenance of hepatocyte function), and in further view of Narkhede et al. (Biomimetic strategies to recapitulate organ specific microenvironments for studying breast cancer metastasis), as applied to claim 4, above, and in further view of Petersen et al. (Matrix Composition and Mechanics of Decellularized Lung Scaffolds).
Regarding claim 6, Skardal et al. discloses wherein the second substrate comprises lung-specific ECM derived from lung tissue, as set forth above.
Skardal et al. is silent as to wherein the second substrate comprises collagen in a concentration of about 400 to about 530 µg/mL, elastin in a concentration of about 40 µg /mL to about 50 µg /mL, and glycosaminoglycan in a concentration of about 3 µg /mL to about 5 µg /mL.
Petersen et al. discloses a method of preparing lung-specific ECM derived from decellularized lung tissue (Abstract), wherein the method is directed towards preserving collagen, elastin, and glycosaminoglycan amounts as these components are important for lung function (Abstract, p. 229 last paragraph-p. 230 first paragraph). Petersen et al. discloses amounts of collagen, elastin, and glycosaminoglycan in the lung-specific ECM (Table 1, p. 225).
It has been held that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation, when the particular parameter is recognized as a result-effective variable (MPEP §2144.05). The prior art discloses general conditions for a concentration of collagen, elastin, and glycosaminoglycan in the context of lung ECM, and one of ordinary skill in the art would recognize the amounts thereof to be a result-effective variable based on the teachings of the prior art, as discussed above. Therefore, it would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to discover through routine experimentation an optimum or workable range for the concentration of each of collagen, elastin, and glycosaminoglycan of the second substrate, in order to arrive at a lung-specific substrate having desired properties.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Skardal et al. (Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform), or alternatively, under 35 U.S.C. 103 as being unpatentable over Skardal et al. (Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform) in view of Skardal et al. (Tissue specific synthetic ECM hydrogels for 3-D in vitro maintenance of hepatocyte function), and in further view of Narkhede et al. (Biomimetic strategies to recapitulate organ specific microenvironments for studying breast cancer metastasis), as applied to claim 4, above, and in further view of Ren et al. (Evaluation of two decellularization methods in the development of a whole-organ decellularized rat liver scaffold).
Regarding claim 7, Skardal et al. discloses wherein the third substrate comprises liver-specific ECM derived from liver tissue, as set forth above.
Skardal et al. is silent as to wherein the second substrate comprises collagen in a concentration of about 1100 to about 1300 µg/mL, elastin in a concentration of about 120 µg /mL to about1 50 µg /mL, and glycosaminoglycan in a concentration of about 5 µg /mL to about 15 µg /mL.
Ren et al. discloses a method of preparing liver-specific ECM from decellularized liver tissue wherein the method is directed towards preserving amounts of collagen, elastin, and glycosaminoglycan in the liver-specific ECM (Abstract). Ren et al. discloses amounts of collagen, elastin, and glycosaminoglycan in the liver-specific ECM (Abstract, Fig. 3, p. 454).
It has been held that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation, when the particular parameter is recognized as a result-effective variable (MPEP §2144.05). The prior art discloses general conditions for a concentration of collagen, elastin, and glycosaminoglycan in the context of liver ECM, and one of ordinary skill in the art would recognize the amounts thereof to be a result-effective variable based on the teachings of the prior art, as discussed above. Therefore, it would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to discover through routine experimentation an optimum or workable range for the concentration of each of collagen, elastin, and glycosaminoglycan of the third substrate, in order to arrive at a liver-specific substrate having desired properties.
Claims 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Skardal et al. (Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform), or alternatively, under 35 U.S.C. 103 as being unpatentable over Skardal et al. (Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform) in view of Skardal et al. (Tissue specific synthetic ECM hydrogels for 3-D in vitro maintenance of hepatocyte function), and in further view of Narkhede et al. (Biomimetic strategies to recapitulate organ specific microenvironments for studying breast cancer metastasis), as applied to claim 4, above, and in further view of Akhmanova et al. (Physical, Spatial, and Molecular Aspects of Extracellular Matrix of In Vivo Niches and Artificial Scaffolds Relevant to Stem Cells Research).
Regarding claim 8, Skardal et al. discloses wherein the second substrate comprises lung-specific ECM derived from lung tissue and the third substrate comprises liver-specific ECM derived from liver tissue, and Skardal et al. in view of Narkhede et al. teaches wherein the first substrate comprises bone-specific ECM derived from bone tissue, as set forth above.
The prior art combination does not disclose or teach the specific elastic moduli numeric values recited in claim 8.
Akhmanova et al. discloses that native liver ECM has an elastic modulus of at most 2-6 kPa (p. 4 column 2 paragraphs 2-3, Table, p. 5), and that the most rigid native ECM is precalcified bone with an elastic modulus of 50 kPa (p. 4 column 2 paragraphs 2-3) (therefore the elastic modulus of native lung ECM must necessarily fall within the range of 0-50 kPa). Akhmanova et al. further discloses elastic moduli of engineered ECM intended to mimic native tissue ECM, all of which fall within the range of 0-3.1 MPa (Table, p. 10). Akhmanova et al. discloses that the elastic modulus of an ECM effects biological activity such as stem cell proliferation (p. 4 last paragraph).
It has been held that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation, when the particular parameter is recognized as a result-effective variable (MPEP §2144.05). The prior art discloses general conditions for the elastic modulus for each of bone-, lung-, and liver-specific ECM, and one of ordinary skill in the art would recognize the elastic moduli thereof to be a result-effective variable based on the teachings of the prior art, as discussed above. Therefore, it would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to discover through routine experimentation an optimum or workable range for the elastic moduli of each substrate, in order to arrive at tissue-specific substrates having desired properties.
Regarding claim 9, Skardal et al. discloses wherein the second substrate comprises lung-specific ECM derived from lung tissue and the third substrate comprises liver-specific ECM derived from liver tissue, and Skardal et al. in view of Narkhede et al. teaches wherein the first substrate comprises bone-specific ECM derived from bone tissue, as set forth above.
The prior art combination does not disclose or teach the specific elastic moduli numeric values recited in claim 9.
Akhmanova et al. discloses that native liver ECM has an elastic modulus of at most 2-6 kPa (p. 4 column 2 paragraphs 2-3, Table, p. 5), and that the most rigid native ECM is precalcified bone with an elastic modulus of 50 kPa (p. 4 column 2 paragraphs 2-3) (therefore the elastic modulus of native lung ECM must necessarily fall within the range of 0-50 kPa). Akhmanova et al. further discloses elastic moduli of engineered ECM intended to mimic native tissue ECM, all of which fall within the range of 0-3.1 MPa (Table, p. 10). Akhmanova et al. discloses that the elastic modulus of an ECM effects biological activity such as stem cell proliferation (p. 4 last paragraph).
It has been held that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation, when the particular parameter is recognized as a result-effective variable (MPEP §2144.05). The prior art discloses general conditions for the elastic modulus for each of bone-, lung-, and liver-specific ECM, and one of ordinary skill in the art would recognize the elastic moduli thereof to be a result-effective variable based on the teachings of the prior art, as discussed above. Therefore, it would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to discover through routine experimentation an optimum or workable range for the elastic moduli of each substrate, in order to arrive at tissue-specific substrates having desired properties.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Skardal et al. (Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform), or alternatively, under 35 U.S.C. 103 as being unpatentable over Skardal et al. (Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform) in view of Skardal et al. (Tissue specific synthetic ECM hydrogels for 3-D in vitro maintenance of hepatocyte function), as applied to claim 1, and in further view of Akhmanova et al. (Physical, Spatial, and Molecular Aspects of Extracellular Matrix of In Vivo Niches and Artificial Scaffolds Relevant to Stem Cells Research).
Regarding claim 11, Skardal et al. discloses the tissue-specific ECM, including liver-specific ECM, as set forth above. Skardal et al. envisions using the platform to model diseased tissue (p. 10 last paragraph-p. 11 second paragraph).
Skardal et al. is silent as to wherein each tissue-specific ECM is derived from fibrotic tissue.
Akhmanova et al. discloses that properties of ECM change with disease such as fibrosis, e.g., fibrotic liver tissue becomes stiffer (p. 4 column 2).
It would have been obvious to one of ordinary skill in the art at the time before the effective filing date of the claimed invention to modify the tissue-specific ECM disclosed by Skardal et al. to be derived from fibrotic tissue, as Akhmanova et al. discloses that ECM changes with fibrosis, and the skilled artisan would have been motivated to use fibrotic tissue to enhance the experimental utility of the platform for modeling diseases such as fibrosis.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Hattori et al. (Microenvironment array chip for cell culture environment screening) is directed to a microfluidic chip comprising a plurality of microfluidic chambers, each chamber comprising an ECM, the chip comprising one or more microfluidic channels communicating with the plurality of microfluidic chambers.
Conclusion
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/HOLLY KIPOUROS/Primary Examiner, Art Unit 1799
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