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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/20/2026 has been entered.
Status of Claims
Claims 1-2, 8-9 and 14 have been amended. Claims 1-9 and 12-16 are examined.
Claim Interpretation
As noted in the Advisory Action 03/27/2026, arguments are drawn to "a Xenopus laevis chip configured for evaluating external fertilization of Xenopus laevis, development of an embryo, and development toxicity" - however, claim 1 as submitted appears to have deleted a line of text after the preamble reciting this chip and configuration. Claims will be interpreted as “a toxicity evaluation system comprising: a Xenopus laevis chip configured for evaluating external fertilization of Xenopus laevis, development of an embryo, and development toxicity".
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-9 and 12-16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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 is unclear because it states that a sample flows and then states circulating a solution and it is unclear if there are both a sample and a solution flowing through the chip or if the solution and sample are the same entity.
Claim 1 is unclear because it recites “containing sperms with spawns” and it is unclear if the spawns are related to the Xenopus laevis egg/embryo previously recited or a different type of spawn.
Claim 1 is indefinite because line 2 recites chip configurations for “evaluating external fertilization of a vertebrate, development of an embryo, and development toxicity” but the claim fails to provide any structural features or correlation to structural components of the chip that allows these configurations and functions to be possible. For example, what is structurally included in the chip that allows it to be configured for evaluating external fertilization of a Xenopus laevis – as currently recited, the solution containing sperms with spawns are not active components of the chip. Further, it is unclear what is structurally included in the chip that allows it be configured for evaluating toxicity or additionally for embryogenesis.
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.
Claim(s) 1-7 and 12-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Novak et al. (US 20190009274, Pub Date: 01/10/2019).
Regarding claim 1, Novak teaches throughout the publication a toxicity evaluation system (see Figure 1; paragraph 0035) comprising:
a Xenopus laevis chip (paragraph 0020) configured for evaluating development of an embryo (paragraph 0020), and development toxicity (paragraph 0035), the Xenopus laevis chip including:
a passage sized to receive a single Xenopus laevis egg or embryo, in which a sample flows (Figure 1, central portion 112; paragraph 0062); and
a plurality of recesses provided on the passage and sized to receive a single Xenopus laevis egg or embryo, and configured to trap objects included in the sample (Figure 1, chamber/embryo trap 114, paragraph 0062; Figure 3) and
a pump configured to inject the sample into the chip (paragraph 0025),
wherein the chip is configured to receive a single Xenopus embryo that will develop in response to exposure to an agent introduced by flow of the culture medium after trapping an embryo of a single entity level in a 3D chip (paragraph 0020), and evaluate a toxicity of a medicine (paragraph 0035).
While Novak does not explicitly teach that the chip is for evaluating external fertilization of a Xenopus laevis or configured to induce fertilization and embryogenesis, such limitations are drawn to functional limitations of the chip and thus the prior art only needs to be capable of performing the functional limitations. Novak teaches that each of the chambers can be sized to receive a single Xenopus embryo that will develop in response to exposure to an agent introduced by flow of the culture medium such that the grown Xenopus remains within the chamber after a fixed period and also teaches the same structure as recited in the claims. Therefore, the reference is considered capable of performing the recited functional language.
Regarding claim 2, Novak teaches the system wherein each of the plurality of recesses has a size to receive a single Xenopus embryo (paragraph 0020). Although Novak does not explicitly teach that the recesses trap an egg in the sample, limitations drawn to the sample are drawn to functional language/intended use of the structural components of the system and thus the reference only needs to be capable of performing the recited functions since the sample has not been actively claimed within the system. Novak teaches that the chambers are sized relative to the desired stage of the Xenopus sample (paragraph 0020) and thus would be capable of trapping an egg in the sample.
Regarding claim 3, Novak teaches the system wherein an inlet port (Figure 1, inlet 108) and an outlet port (Figure 1, outlet, 110) are formed at one end and an opposite end of the passage (see Figure 1 and paragraph 0062).
Regarding claim 4, Novak teaches the system wherein the passage is a combination of a first passage having a first width and a second passage having a second width, wherein the first width has a size, by which the objects included in the sample flow, and wherein the second width has a size, by which the objects included in the sample is prevented from flowing (see Figure 1 and paragraphs 0140-0141).
Regarding claim 5, Novak teaches the system wherein the recesses are provided in a direction that faces the outlet port from the inlet port (see Figure 1).
Regarding claim 6, Novak teaches the system wherein the pump causes the sample to flow in any one of a first direction or a second direction (paragraph 0025 and more specifically, paragraph 0152).
Regarding claim 7, Novak teaches the system wherein the sample is a pharmaceutical sample, by which a toxicity is evaluated (paragraph 0035 and 0160).
Regarding claim 12, Novak teaches the system wherein the chip functions as an incubator (paragraph 0123). While Novak does not explicitly teach that the incubator function increases probability of fertilization during external fertilization, such limitation is drawn to intended use of the system and thus the prior art only needs to be capable of performing the recited intended use. Novak teaches the same structural limitations and that the specimens in the chambers can be maintained and/or grown under cell culture conditions (paragraph 0123) and thus would be capable of performing the recited intended use.
Regarding claim 13, Novak teaches the system wherein the pump is configured to supply therapeutic substances or biomolecules (paragraph 0035) at a uniform velocity through a fluid circulation system (paragraphs 0025 and 0150-0152).
Regarding claim 14, while Novak does not explicitly teach that the system is configured to enable extraction of a tadpole out of the chip in a reverse direction relative to a direction from an inlet port toward an outlet port, such limitation is a functional limitation of the claimed system. Novak teaches the same structural components of the claims and further teaches that the plurality of chambers are sized based on the desired growth stage of the Xenopus (paragraph 0020) and that the pump has configurations for various flow directions based on the fluids/samples being introduced/removed (paragraph 0152-0153). Therefore, Novak is seen as capable of performing the functions of the claim.
Regarding claim 15, while Novak does not specifically teach that the pump is configured to circulate the sample for several hours or several days at a constant velocity, such limitation is drawn to intended use of the system. So long as the system of Novak is capable, it reads on the claims. Novak teaches the same structural components as claimed and a pump system for flowing samples/fluids at various velocities depending on the fluid and specimens trapped (paragraphs 0124 and 0152-0153). Therefore it is considered capable of performing the same intended use.
Regarding claim 16, Novak teaches the system wherein the chip is configured to control physical movements of eggs and embryos at a single entity level (paragraphs 0019-0020 and 0148).
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.
Claim(s) 8-9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Novak et al. (US 20190009274, Pub Date: 01/10/2019), as applied to claims 1-2 above, and further in view of Han et al. (Lab Chip 2010, 10, pages 2848-2854, IDS).
Regarding claims 8-9, Novak teaches a method of performing a toxicological evaluation by using the toxicity evaluation system of claim 2 (see rejection above), the method comprising: trapping the specimens in the plurality of recesses by injecting a solution containing the specimens into the chip (paragraph 0020) as well as controlling sample and fluid flow with the use of a pump system (paragraphs 0150-0152). However, Novak does not specifically teach inducing in vitro fertilization by injecting a solution containing sperms that fertilize spawns into the chip; and injecting a sample for evaluating toxicity of a Xenopus laevis organism, on which the in vitro fertilization has been completed and further comprising: injecting a toxicity evaluation sample for evaluating a toxicity of the Xenopus laevis organism, on which the in vitro fertilization has been completed, into the passage; trapping the Xenopus laevis organism, on which the in vitro fertilization has been completed, by the recesses, by adjusting the pump such that the sample flows in a first direction and causing the Xenopus laevis organism, on which the in vitro fertilization has been completed, to escape, by adjusting the pump such that the sample flows in a second direction.
Han teaches a method for performing in vitro fertilization and development evaluation (page 2852, right column, fertilization and development status of each oocyte can be tracked as well as abnormal development can be studied), the method comprising: trapping the spawns in the plurality of recesses by injecting the solution containing the spawns into the chip; and inducing in vitro fertilization by injecting the solution containing the sperms that fertilize the spawns into the chip (pages 2851-2852, sections 3.3 and 3.4), further comprising: injecting a sample for evaluating a toxicity of an organism, on which the in vitro fertilization has been completed, into the passage (page 2850, sections 2.4-2.6) and trapping the organism, on which the in vitro fertilization has been completed, by the recesses, by adjusting the pump such that the sample flows in a first direction (page 2850, section 2.6 second and third paragraph) and causing the organism, on which the in vitro fertilization has been completed, to escape, by adjusting the pump such that the sample flows in a second direction (page 2850, section 2.6, last paragraph).
It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was filed to incorporate within the chip and toxicity evaluation methods of Novak, in-vitro fertilization analysis as taught by Han because it would have been desirable to bring several advantages of microfluidic technology to IVF practices by simplifying oocyte handling and manipulation, allowing rapid and convenient medium changing and enabling automated tracking of single embryo development (Han, abstract).
Response to Arguments
Applicant’s amendments and remarks filed 04/20/2026 have been considered.
Firstly, Applicant argues that Novak does not disclose or teach circulating a solution containing sperms with spawns located in the passage to induce fertilization. This argument is not persuasive because the argued solution is not an actively claimed component of the chip and thus is drawn to intended use of the chip. Novak teaches the same structural components and configuration as described in the claims and thus would be capable of flowing a solution in the passage. Additionally, applicant argues that since Novak is designed for exposing pre-existing embryos that it does not read on the claimed chip. This argument is also not persuasive because the claim clearly states that the passage or recesses can hold an egg or embryo, which is also structurally taught by Novak.
Applicant also argues that claim 1, as amended, requires the chip to be configured to induce fertilization by circulating a solution containing sperms with spawns located in the passage, which is a structural configuration that enables on-chip fertilization through sperm circulation. Examiner disagrees with this assertion as the argued configuration provides no structural components of the chip but rather that the chip is used for flow a solution containing sperms with spawns – which Novak is structurally capable of doing given the presence of the passages and recesses, as described in the rejection above.
Regarding claims 8-9, Applicant argues that Novak in view of Han fail to teach the claimed invention because Han’s method uses gravity driven flow and pipette manipulation which is fundamentally different from the claimed method. This argument is not persuasive because one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Han is cited for the teachings of in-vitro fertilization and when the fertilization methods of Han are incorporated on the chip of Novak that has the structure capable for fertilization, the combination reads on the claimed methods, as described above.
Examiner recommends finding structural components of the chip, supported by the specification, that provides the chip with capabilities for conducting the claimed functions. For example, chip dimensions, specific solutions, structural pump configurations that allow various solutions to be moved relative to other structural components of the chip.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA M GIERE whose telephone number is (571)272-5084. The examiner can normally be reached M-F 8:30-4:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy L Nguyen can be reached at 571-272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/REBECCA M GIERE/Primary Examiner, Art Unit 1677
