DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1/13/2026 has been entered.
Claims status
Claims 3 and 45 is/are cancelled and claim 47 is newly added. 1, 4, 8-12, 16, 20, 23, 24, 28, 29, 37, 40-43, 46 and 47 is/are currently pending with claims 23, 24, 28, 29, 37, 40-43 is/are withdrawn. Claims 1, 4, 8-12, 16, 20, 46, 47 is/are under examination.
Each amendment document that includes a change to an existing claim, must include markings to indicate the changes that have been made relative to the immediate prior version. See MPEP § 714(II)(c) and (f). Amendments which fail to comply with the requirements of 37 CFR 1.121 are considered noncompliant. In the present application claims 11 is amended but lacks markings to indicate the changes that have been made relative to the immediate prior version (See prior claim 11 at top vs instant claim 11 below it).
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In comparing the two claims, “and/or” in line 3 of prior Claim 11 appears to be removed from the instant claim 11. However, this appears to be an inadvertent deletion and thus, in the interest of compact prosecution, the present claim 11 is examined with “and/or” in line 3.
Claim Objections
Claim 1 and 12 are objected to because of the following informalities: The claims recite “one or more phenotypes for cardiovascular diseases”. Genotypes have phenotypes while diseases have symptoms. However, the list following this phrase are various types of cardiovascular diseases and not a “phenotype” or symptoms of any cardiovascular disease. Following language is recommended: ““one or more . Appropriate correction is required.
Claim 11 is objected to because of the following informalities: The claim lacks a proper conjunction to separate the listed limitations. As noted above, it appears that an “and/or” conjunction was inadvertently deleted from this claim and thus it is recommended that this conjunction be used in this claim. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Rejection of Claims 12, 16 and 45 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 is withdrawn in light of claim amendment or cancellation.
Claims 1, 4, 8-11, 16, 20, 46, 47 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 recites a device wherein hiPSC-vECs could be in first or second channel (lines 7-9) and hiPSC-CMs could also be wither in first or second channel (lines 10-12). Claim also recites “wherein the hiPSC-vECs and the hiPSC-CMs in different channels are capable of recapitulating” certain recited phenotypes. It is unclear if the claim requires the hiPSC-vECs and the hiPSC-CMs to be in separate channels to recapitulate the recited phenotypes or if this is a contingent limitation such if the hiPSC-vECs and the hiPSC-CMs are in separate channels then they recapitulate the recited phenotypes. Alternatively, if one or both channels could comprise one or both of these cell types, then it is unclear if hiPSC-vECs in one channel with the hiPSC-CMs in the other channel recapitulate the recited phenotypes. The specification discloses embodiments wherein hiPSC-vECs and the hiPSC-CMs are in separate channels (Figure 7, 9, 20). For the purpose of compact prosecution, the claim(s) 1 is/are interpreted as “wherein the hiPSC-vECs and the hiPSC-CMs are in different channels and are capable of recapitulating”.
Claims 4, 8-11, 16, 20, 46, 47 is/are rejected due their dependence on claim 1 because they do not clarify the 112b issue noted with claim 1.
Claim Rejections - 35 USC § 112(a) – New Matter
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.
Claims 9, 10 and 47 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. 37 CFR 1.118 (a) states that “No amendment shall introduce new matter into the disclosure of an application after the filing date of the application”.
Claim 9 has been amended to recite “wherein the first channel and the second channel are integrated such that fluid introduced to the device flows from the second channel to the first channel.” Claim 10 depends from claim 9 and incorporates this new limitation. New claim 47 recites “wherein the at least one inlet port, the first channel, the second channel, and the at least one outlet port are configured to cause the fluid to flow from the hiPSC-vECs to the hiPSC-CMs.”.
The originally filed specification does not disclose an embodiment wherein the flow of the fluid is required to be directed from one specific channel or cell type to another. Although Applicant indicates that no new matter is added (reply 1/13/2026; page 7, para 1) but they do not identify wherein the specification support for these new limitation could be found, either explicitly or implicitly.
MPEP 2163.06 notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).” MPEP 2163.02 teaches that “Whenever the issue arises, the fundamental factual inquiry is whether a claim defines an invention that is clearly conveyed to those skilled in the art at the time the application was filed...If a claim is amended to include subject matter, limitations, or terminology not present in the application as filed, involving a departure from, addition to, or deletion from the disclosure of the application as filed, the examiner should conclude that the claimed subject matter is not described in that application. MPEP 2163.06 further notes “When an amendment is filed in reply to an objection or rejection based on 35 U.S.C. 112, first paragraph, a study of the entire application is often necessary to determine whether or not “new matter” is involved. Applicant should therefore specifically point out the support for any amendments made to the disclosure [or point to case law supporting incorporation of such a limitation as in the instant case]” (emphasis added).
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.
Rejection of Claim(s) 3 under 35 U.S.C. 102(a)(1) as being anticipated by Ingber et al (US 2014/0342445 A1, Nov 20, 2014; IDS 10/26/2022) is moot due to claim cancellation.
Previous rejection of Claim(s) 1, 4, 8-12, 16, 20 under 35 U.S.C. 102(a)(1) as being anticipated by Ingber et al (US 2014/0342445 A1, Nov 20, 2014; IDS 10/26/2022) is withdrawn due to amendment to claim 1 which is addressed in the New Grounds of rejection below.
Claim(s) 1, 3, 4, 8-12, 16, 20, 47 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ingber et al (US 2014/0342445 A1, Nov 20, 2014; IDS 10/26/2022).
Regarding claim 1, Ingber discloses a device comprising a membrane, which owing to its planar nature inherently comprises two sides or in other words, a top/bottom surface (= claimed membrane with top and bottom surface; [0055], [0059]). Ingber discloses embodiments wherein the membrane separates two sub-channels (=claimed first and second channels parallel to the membrane and in communication with top and bottom surfaces of the membrane respectively). Ingber discloses each side of the membrane is seeded with different cell types i.e. each of the two sub-channels are seeded with different cell types [0059]. In an embodiment, Ingber discloses the two sub-channels as Microvascular channel (seeded with vascular endothelial cells, vECs) and an Interstitial channel (Seeded with organ-specific parenchymal cells such as cardiac muscle cells i.e. cardiomyocytes, CMs) ([0059], [0069], [0077], [0086], [0109], Figures 2, 8, 9). Since the membrane forms a wall of each of the sub-channel, the sub-channels and the membrane are fluidically connected. Regarding the cell sources for the vascular endothelial cells and organ-specific parenchymal cells such as cardiac muscle cells, Ingber discloses embodiment wherein the cells are derived from iPS and, further disclose human cardiomyocytes and human endothelial cells (=hiPSC-vECs and hiPSC-CMs; [0059], [0069], [0077], [0086], [0109], [0114], [306]). Taken together, Ingber discloses hiPSC-vECs and hiPSC-CMs in separate channels.
Additionally, Ingber discloses embodiment wherein the cells are derived from a subject for personalized therapeutic treatment ([0012], [0087], [0114], [0127], [233], [301], [306]). Ingber also discloses embodiment wherein their device is used for disease modelling by integrating diseased cells [128, 180] and to test toxic effects of chemotherapy agents, such as trastuzumab, and arrythmia-inducing agents, such as terfenadine [0040, 125, 128, 129, 130]. Thus, hiPSC-vECs and the hiPSC-CMs in Ingber’s device are capable of recapitulating, at the cellular level, one or more cardiovascular diseases, such as at least chemotherapy-induced cardiomyopathy, Brugada syndrome, long-QT syndrome. Furthermore, since Ingber teaches deriving cells are derived from a subject with diseases, Ingber’s device is inherently capable of recapitulating, at the cellular level, other claimed cardiovascular diseases.
Regarding claim 4, Ingber discloses a device comprising at least an inlet and an outlet port, wherein the inlet introduces culture medium into the channels i.e. in fluidic communication with a channel and its membrane surface and, wherein outlet port is for a fluid to exit [0064].
Regarding claim 8, Ingber discloses fabricating the device with polydimethylsiloxane (PDMS) i.e. channels comprise PDMS ( [0054].
Regarding claim 9, Ingber discloses a device comprising at least an inlet and at least two channels separated by a porous membrane that allows for transfer of fluids [0049, 0056, 0069, 0090, 109]. Since the membrane separating the two channels is porous, fluid that is introduced in one channel, such as a second channel, flows to the other channel, such as a first channel.
Regarding claim 10, Ingber discloses hiPSC-CMs that inherently the represent myocardium and hiPSC-vECs that inherently represent systemic vasculature [0059], [0069], [0077] 0086], [0109], [0114], [306]). Ingber also discloses each side of the membrane is seeded with different cell types i.e. each of the two sub-channels are seeded with different cell types such that hiPSC-CMs and hiPSC-vECs would be in separate channels such as hiPSC-CMs in a first channel while hiPSC-vECs in a second channel [0059].
Regarding claim 11, Ingber discloses embodiments wherein device is microfluidic i.e., comprises microfluidic channels [0034, 0107], membrane comprises PDMS [0058], cells express fluorescent reporters [0089].
Regarding claim 16, Ingber discloses seeding cells on Matrigel, an extracellular matrix gel [0057, 0060].
Regarding claim 20, Ingber discloses embodiment wherein the cells are derived from iPS and, further disclose human cardiomyocytes and human endothelial cells ([0086], [0109], [0114]). The markers listed in the claims for hiPSC-EC, such as CD31,CD34,VEGF, VEGFA, are inherent to the cell type of hiPSC-EC which is disclosed by Ingber. Thus, Ingber discloses hiPSC-EC which inherently express CD31, CD34, VEGF, VEGFA.
Regarding claim 12, Ingber discloses heart organ (i.e. cardiovascular) chip device comprising a membrane separating two sub-channels i.e. Microvascular channel (seeded with vascular endothelial cells representing system vasculature) and an Interstitial channel (Seeded with organ-specific parenchymal cells such as cardiac muscle cells i.e. cardiomyocytes representing myocardium) wherein the vascular ECs and cardiomyocytes could be iPSC-derived ([0059], [0069], [0077], [0105], [0109]). Additionally, Ingber discloses embodiment wherein the cells are derived from a subject for personalized therapeutic treatment ([0012], [0087], [0114], [0127], [301], [306]) (=patient specific). Additionally, Ingber discloses embodiment wherein the cells are derived from a subject for personalized therapeutic treatment ([0012], [0087], [0114], [0127], [233], [301], [306]). Ingber also discloses embodiment wherein their device is used for disease modelling by integrating diseased cells [128, 180] and to test toxic effects of chemotherapy agents, such as trastuzumab, and arrythmia-inducing agents, such as terfenadine [0040, 125, 128, 129, 130]. Thus, hiPSC-vECs and the hiPSC-CMs in Ingber’s device are capable of recapitulating, at the cellular level, one or more cardiovascular diseases, such as at least chemotherapy-induced cardiomyopathy, Brugada syndrome, long-QT syndrome. Furthermore, since Ingber teaches deriving cells are derived from a subject with diseases, Ingber’s device is inherently capable of recapitulating, at the cellular level, other claimed cardiovascular diseases.
Regarding claim 47, Ingber discloses a device comprising at least an inlet, at least two channels separated by a porous membrane that allows for transfer of fluids and at least one outlet [0049, 0056, 0064, 0069, 0090, 109]. Ingber also discloses each side of the membrane is seeded with different cell types i.e. each of the two sub-channels are seeded with different cell types such that hiPSC-CMs and hiPSC-vECs would be in separate channels such as hiPSC-CMs in a first channel while hiPSC-vECs in a second channel [0059]. Since the membrane separating the two channels is porous, fluid that is introduced in one channel, such as a second channel comprising hiPSC-ECs, flows to the other channel, such as a first channel comprising hiPSC-CMs.
Therefore, Ingber anticipates the claimed invention.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Rejection of Claim(s) 45 under 35 U.S.C. 103 as being unpatentable over Ingber as applied to claim 1 above, and further in view of Roberts et al (Stem Cell Reports. Vol. 12, 1145–1158, May 14, 2019) is moot due to claim cancellation.
Rejection of Claim(s) 46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ingber as applied to claim 1 above, and further in view of Roberts et al (Stem Cell Reports. Vol. 12, 1145–1158, May 14, 2019) is withdrawn in light of withdrawal of the rejection that the instant rejection relied upon..
Claim(s) 46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ingber as applied to claim 1 above, and further in view of Roberts et al (Stem Cell Reports. Vol. 12, 1145–1158, May 14, 2019; ref of record).
The teachings from Ingber as applied to claim 1 above are relied upon for the instant rejection.
Regarding claim 46, Ingber teaches “the cells used in the organ chips can be genetically engineered for various purposes, e.g. to express a fluorescent protein” [0089].
Ingber does not teach hiPSCs or any of the cell types derived from hiPSCs (iPSC-EC, iPSC-CC, iPSC-vEC, iPSC-CMs) to comprise an alpha-actinin-GFP reporter.
Roberts teaches hiPSC with alpha-actinin-GFP that allow for visualization of sarcomere in cardiomyocytes derived from these iPSCs (page 1147, col. 1, para 1; Figure S3)
Therefore, it would be obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use Roberts’ hiPSC with alpha-actinin-GFP to derive CMs to use in Ingber’s device. An ordinary artisan would be motivated to use Roberts’ iPSC because it would allow for visualization of the CMs using the GFP reporter. An ordinary artisan would reasonably expect to derive CMs from Robert’s iPSC because Roberts’ derives CMs from their iPSC (Figure S3) and furthermore, an ordinary artisan would simply substitute Ingber’s non-fluorescent iPSC-CM in their device with Robert’s fluorescent iPSC-CM.
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.
Response to Arguments
Applicant's arguments filed 1/13/2026 with regards to U.S.C. 102 rejection of the claims 1, 3, 4, 8-12, 16, and 20 have been fully considered but they are not moot due to new grounds necessitated by claim amendments.
Pertinent to instant rejection U.S.C. 102 rejection of the claims 1, 3, 4, 8-12, 16, 20, 47 Applicant argue that Ingber fails to disclose the newly added feature recited in amended claim 1 i.e. “wherein the hiPSC-vECs and the hiPSC-CMs in different channels are capable of recapitulating, at the cellular level, one or more phenotypes for cardiovascular diseases." (page 8, para 3). In response, as detailed in the instant U.S.C. 102 rejection above, Ingber teaches this limitation.
Applicant's arguments filed 1/13/2026 with regards to U.S.C. 103 rejection of the claims 45 and 46 have been fully considered but they are not moot due to new grounds necessitated by claim amendments.
Pertinent to instant rejection U.S.C. 103 rejection of the claims 46 Applicant argue that Roberts fails to cure Ingber deficiency of not teaching the newly added claim limitation (page 8, last para). In response, as detailed in the instant U.S.C. 102 rejection above, Ingber teaches the new limitation thus does not suffer from the alleged deficiency.
It is noted that the Applicant requests that the restriction requirement be withdrawn since the nonelected process claims contain all the limitations of an allowable product/apparatus claim and would not be a serious search or examining burden. (page 9). However, claims are not found to be allowable.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATASHA DHAR whose telephone number is (571)272-1680. The examiner can normally be reached M-F 8am-4pm (EST).
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/MATASHA DHAR/Examiner, Art Unit 1632
Prosecution Insights