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 5-7 and 23 are cancelled.
Claims 1-4, 8-22, and 24 are pending.
Claims 1 and 20-21 are amended.
Applicant’s election without traverse of Group I, claim(s) 1-4, 8-9, 20-22, and 24, in the reply filed on 01/28/2026 is acknowledged. Applicant’s election of species, as follows:
DNA oxidative stress markers from the options recited in instant claim 12;
8-OHdG from claim 13; and
The step of detecting aneuploidy from claim 19,
in the reply filed on 01/28/2026 is acknowledged.
Claims 10-11 and 14-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Groups/Inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/28/2026. It is noted that the 01/28/2026 claim amendments of claims 2 and 12-13 so transform the claims from being classified in non-elected Group II into elected Group I.
Claims 1-4, 8-9, 12-13, 20-22, and 24 are under examination on the merits.
Priority
This application is a 371 of PCT/US2021/056046 10/21/2021, which claims benefit of US Provisional Application NO. 63/126,108, filed 12/16/2020 and claims benefit of US Provisional Application NO. 63/104,228, filed 10/22/2020.
Newly Necessitated-Notice
It is noted that Applicant appears to have indicated that claims 12-13 are withdrawn. The Examiner has not withdrawn claims 12-13 and maintains that the claims remain under Examination on the merits.
Withdrawn Objections/Rejections
The objection to claim 21 is withdrawn in light of the corrective claim amendments dated 07/06/2026. The objection to the specification is withdrawn in light of the corrective amendments dated 07/06/2026. The rejection of claim 21 under 35 USC §112 (b) is withdrawn in light of the corrective claim amendments dated 07/06/2026.
Maintained-Claim Interpretation
Note the expansive definition ‘measuring/assaying/assessing/determining/analyzing’ at paragraph 0044 of the specification, and note the further descriptive definitions at paragraphs 0062-0063 of the specification. Recitations of ‘measuring/determining/assaying/analyzing’ will be understood in accordance with the notably broad definition provided by the cited portions of the instant specification.
Claim Rejections - 35 USC § 112
Newly Necessitated-35 USC § 112(a)
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 1-4, 8-9, 12-13, 20-22, and 24 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. This is a new matter rejection.
The Examiner is unable to find support for the added limitation in claims 1 and 20 (incorporated via dependency in their respective, dependent claims) i.e., “a sensor reader…configured to determine…one or more of a developmental potential of the embryo, a developmental competence of the embryo, a viability of the embryo, a health of the embryo, an implantation potential of the embryo, and an oxidative stress of the embryo”. Applicant makes no statement in the remarks indicating where support for the claim amendments may be found and further dos not state that no new matter has been added. The only disclosure in the specification is that the sensor reader may be connected to a sensor and may display data regarding pH, electrolytes, oxygen and/or temperature (see exemplary pages 21-22 of the instant specification). Applicant is required to cancel the new matter in response to this office action.
Should applicant disagree with the Examiner’s factual determination above, applicant should provide evidence that either or both of the provisional applications provide support for the invention now claimed in the manner required by 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. This could be accomplished, for example, by pointing to the specific page and line numbers within the specification, which disclose each limitation of the claimed invention.
Newly Necessitated-Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are:
“a sensor reader that displays information from the pH sensor, wherein the sensor reader is connected to the pH sensor and is configured to determine, based on the pH of the embryo, one or more of a developmental potential of the embryo, a developmental competence of the embryo, a viability of the embryo, a health of the embryo, an implantation potential of the embryo, and an oxidative stress of the embryo” in each of claims 1 (incorporated by dependency into the claims depending from claim 1) and 20 (incorporated by dependency into the claims depending from claim 20).
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
The "sensor reader that displays information from the pH sensor, wherein the sensor reader is connected to the pH sensor and is configured to determine, based on the pH of the embryo, one or more of a developmental potential of the embryo, a developmental competence of the embryo, a viability of the embryo, a health of the embryo, an implantation potential of the embryo, and an oxidative stress of the embryo" in claims 1 and 20 is interpreted as a generic computer application, display screen, and/or means for reading a sensor to which the sensor reader is connected and displaying information from the sensor, the sensor reader displaying information about pH, oxygen and/or temperature, and/or electrolytes described in exemplary pages 21-22 of the specification and equivalents thereof (which are not imported as limitation, but are rather exemplary of the only embodiments described throughout the specification).
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Maintained-35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 21 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 21, depending from claim 20, which depends from claim 1, only adds the limitation of written materials comprising instructions (no further structures/reagents/components or active steps are added or required). The MPEP provides that “…where the printed matter and product do not depend upon each other, no functional relationship exists. For example, in a kit containing a set of chemicals and a printed set of instructions (written materials comprising instructions) for using the chemicals, the instructions are not related to that particular set of chemicals,” (see In re Ngai, 367 F.3d at 1339, 70 USPQ2d at 1864; see also MPEP §2111.05(I)(B)). Here, the kit of claim 20 and the instructions of claim 21 for using the kit do not depend upon one another, but are analogous to the chemical kit and instructions described as having no relationship by the MPEP. Therefore, there being no functional relationship of dependence, the instructions of claim 21 are not given patentable weight. Thus, claim 21 does not further limit the claim(s) from which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
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.
Claim(s) 1-2, 4, 8-9, 20-22, and 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Perozziello et al (Microelectronic Engineering, Volume 98, 2012, Pages 655-658; ISSN 0167-9317; https://doi.org/10.1016/j.mee.2012.07.027; citation 3 under Non-Patent Literature on the IDS dated 12/003/2024) in view of Klein et al (US 7374725 B2).
Regarding claim 1, Perozziello et al teach an in vitro fertilization system for measuring pH having a reservoir for holding cultured cells/embryos, a pH sensor at the bottom (a position) of the reservoir and a sensor reader that displays information from the pH sensor (where measurement of pH from culture media is measurement of the external pH of the embryo/pH of the embryo as described by the instant specification (see for example, paragraph 0018 at page 3, paragraph 0024 at page 4 (detailing figures 3A-3B), paragraph 0047 at page 10, paragraph 0052 at page 11, paragraph 0081 at page 20, page 22, and paragraph 0089 at page 26 of the instant specification), the sensor reader (computer) being connected (implied by teachings, cited herein, of continuous logging and monitoring and the graphical abstract) to the sensor and recording pH and temperature data separately for each device (see for example, the abstract at page 655 and page 656 at Figure 1; showing a system for pH measurement) of an embryo (see for example, Figures 1-2 and their captions at page 656, pages 656-657, and the abstract at page 655). Perozziello et al teach that temperature and pH are continuously logged and monitored and show a reader (computer monitor; noting that the instant specification mentions a reader 9 times with no explicit definition or description of connection to the reader or the reader that would exclude or distinguish the teachings of Perozziello et al over the claimed system regarding nonobviousness) displaying temperature and pH data (while a connection between the sensor is not explicitly shown, it is implied and would have been made obvious to the artisan) (see for example, the abstract and graphical abstract of Perozziello et al). Note that there is no disclosure of a sensor reader configured to determine, based on the pH of the embryo, one or more of a developmental potential of the embryo, a developmental competence of the embryo, a viability of the embryo, a health of the embryo, an implantation potential of the embryo, and an oxidative stress of the embryo (see the rejection under 35 USC §112(a) above) and that the sensor reader/display of Perozziello et al is deemed to meet the structural limitations of the sensor reader as generically recited and is therefore deemed to be configured to determine, based on the pH of the embryo, one or more of a developmental potential of the embryo, a developmental competence of the embryo, a viability of the embryo, a health of the embryo, an implantation potential of the embryo, and an oxidative stress of the embryo, at least as an equivalent means (see the rejection under 35 USC §112(f)).
While Perozziello et al show that the sensor is at the bottom of the sample port which is connected to the wells (functioning top sample media in a way that appears functionally equivalent to having the sensor integrated into the bottom of one or more wells), Perozziello et al do not teach that the sensor may be at the bottom of each of the one or more well(s) and does not explicitly teach that the sensor is at the bottom of the reservoir holding the embryo (making the well itself, the reservoir as instantly claimed).
However, Klein et al teach a well plate reactor having a plurality of wells (reservoirs) and at least one of a pH level sensor and a dissolved oxygen sensor disposed on the interior of the bottom surface of the well, where the pH measured by the sensor is determined by the processor (held to read on the recited reader in the noted absence of a preclusive definition) (see for example, the abstract, column 13, and Figs 3 and 16 at sheets 1 of 10 and 8 of 10).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the combined references before the effective filing date of the claimed invention. The artisan would have been motivated to make and use the invention of Perozziello et al to enable research and enjoy the considerable technical and economic potential in the assisted reproductive technology for human beings as taught by Perozziello et al (see for example, the conclusion section at page 658), where inclusion of a processor/computer/reader would have been obvious to enable ease of observing the measurement and and/or to control variables pertaining to the embryo-culture environment based upon measurements of stress variables such as pH (see for example, page 656 of Perozziello et al teaching that it is expected that the cells in the system are exposed to minimized physical stress and that metabolic waste products can be continuously removed due to the dynamic flow conditions; and paragraph 2 of the background at column 1 of Klein et al). The system of Klein is taught to be valuable for culturing mammalian cells (see for example, column 1 of Klein et al) such that the artisan would have expected to system of Klein et al to be compatible for adaptation according to the teachings of Perozziello et al. The resulting system reads upon and makes obvious the instantly claimed system for measuring pH of an embryo in in vitro culture. The artisan would have understood and found it obvious that the system of Klein, placing a sensor at the bottom of each well, allows for clear and relatively uncontaminated data collection for each, individual embryo while connection of the sensor to a computer/processor with a monitor allowing for continuous logging and monitoring of data, creates convenient ease of data access and allows for trends to be observed by the artisan. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Regarding claim 2, note that the one or more sensors for measuring one or more electrolytes, oxygen sensor, temperature sensor, and one or more sensors for measuring one or more markers of oxidative stress in a cell of the embryo are being interpreted as members of a Markush group such that art teaching any one of the recited sensors makes obvious the claim as instantly drafted.
As discussed above, Klein et al teach a well plate reactor having a plurality of wells (reservoirs) which may have a dissolved oxygen sensor (held to read on the recited oxygen sensor in the absence of a preclusive definition and because the oxygen, from the disclosure read in its entirety, is being measured from the media and is, therefore, understood by the artisan to be dissolved oxygen) disposed on the interior of the bottom surface of the well (see for example, the abstract, column 13, and Figs 3 and 16 at sheets 1 of 10 and 8 of 10). Therefore, instant claim 2 would have been obvious over the cited teachings with a reasonable expectation of success before the effective filing date of the invention.
Regarding claim 4, Perozziello et al teach that temperature and pH are continuously logged and monitored and show a reader (computer monitor; noting that the instant specification mentions a reader 9 times with no explicit definition or description of connection to the reader or the reader that would exclude or distinguish the teachings of Perozziello et al over the claimed system) displaying temperature and pH data (while a connection between the sensor is not explicitly shown, it is implied and would have been made obvious before the effective filing date of the invention to the artisan) (see for example, the abstract and graphical abstract of Perozziello et al).
Regarding claim 8, Perozziello et al further teach that the system comprises one or more incubators and culture/cell media (noting the absence of any requirement/description/definition of an incubator or culture media is provided in the instant disclosure that would preclude the cited teachings from making obvious instant claim 8 or distinguish the prior art over the instant claim) (see above and, for example, Perozziello et al at the abstract of page 655 and Figures 1-2 and their captions at page 656). Therefore, instant claim 8 would have been obvious over the cited teachings with a reasonable expectation of success before the effective filing date of the invention.
Regarding claim 9, Perozziello et al teach that the pH sensor comprises an electrode (see for example, the abstract at page 655 and pages 656-657). Additionally/alternatively, Klein et al teach that the sensors, such as the pH sensor, may be fluorescent tags that can be deposited as small dots on the bottom of the well (a functionalized surface)(see for example, column 5 at lines 30-55). Klein et al further teach an alternative embodiment where the pH sensor may be a pH sensor dye (understood to read on a pH-sensitive dye as instantly recited) embedded into a film deposited within the well (see for example, column 5 at lines 55-65). Th pH sensor may also comprise an indicator material and a reference material having different half-lives (see for example, column 11). Any of the pH sensors of Perozziello et al and Klein et al would have been understood by the artisan to be functional equivalents, obvious for use in the prior art system with a reasonable expectation of success. Therefore, instant claim 9 would have been obvious over the cited teachings with a reasonable expectation of success before the effective filing date of the invention.
Regarding claim 20, while Perozziello et al and Klein et al do not specifically use the language “kit” as recited at the claim preamble, in the instant case, it is noted the terminology “kit” is not found to further limit the scope of the claims beyond requiring limitations required by the system of instant claim 1, as it does not clearly invoke any additional ingredients/components/reagents or provide the antecedent basis for terms appearing in the body of the claim (such as specific packaging or container elements, for example). See MPEP 2111.02. Consequently, when the claims are given their broadest reasonable interpretation, because Perozziello et al and Klein et al teach/make obvious the same structural components that applicant refers to as a kit, the teachings of Perozziello et al and Klein et al addressed and made obvious, before the effective filing date of the invention, the claimed elements/limitation even though the references does not employ the word “kit” in describing their invention, as the reference teaches all necessary reagents of the claimed “kit”.
Regarding claim 21, the added limitation over claim 20 is the recitation of ‘written materials comprising instructions’. The MPEP provides that analysis of printed materials follows a two-prong analysis. The first step of the printed matter analysis is the determination that the limitation in question is in fact directed toward printed matter (see In re DiStefano, 808 F.3d 845, 848, 117 USPQ2d 1265, 1267 (Fed. Cir. 2015); see also MPEP §2111.05). Here, the limitation added by instant claim 21 is the addition of printed instructions, so the answer is yes. “[O]nce it is determined that the limitation is directed to printed matter, [the examiner] must then determine if the matter is functionally or structurally related to the associated physical substrate, and only if the answer is ‘no’ is the printed matter owed no patentable weight,” (Id. at 850, 117 USPQ2d at 1268; see also MPEP §2111.05). “…[W]here the printed matter and product do not depend upon each other, no functional relationship exists. For example, in a kit containing a set of chemicals and a printed set of instructions for using the chemicals, the instructions are not related to that particular set of chemicals,” (see In re Ngai, 367 F.3d at 1339, 70 USPQ2d at 1864; see also MPEP §2111.05(I)(B)). Here, the kit of claim 20/system of claim 1 and the instructions of claim 21 for using the kit do not depend upon one another, but are analogous to the chemical kit and instructions described as having no relationship by the MPEP. Therefore, there being no functional relationship of dependence, the instructions of claim 21 are not given patentable weight and the recitation of claim 21 would have been made obvious before the effective filing date of the invention by the combined teachings of Perozziello et al and Klein et al for the same reason that the kit of instant claim 20 and the system of instant claim 1 are made obvious by said combined references.
Regarding claim 24, both Perozziello et al and Klein et al teach the use/inclusion/importance of culture media for embryo/cell culture (see for example, the abstract at page 655 and figures 1-2 and their captions at page 656 of Perozziello et al; see also, for example, columns 1 and 14 of Klein et al). Therefore, the artisan would have found it obvious before the effective filing date of the invention to include culture media as taught by both Perozziello et al and Klein et al.
Claim(s) 2-4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Perozziello et al and Klein et al, as applied to claims 1-2, 4, 8-9, 20-22, and 24, in view of Hernandez-Ibanez (Biosensors and Bioelectronics 77 (2016) 1168–1174; http://dx.doi.org/10.1016/j.bios.2015.11.005).
Regarding claims 2-4, Perozziello et al and Klein et al teach as set forth above.
Perozziello et al and Klein et al do not teach sensors or measurement of electrolytes, such as pyruvate or lactate.
However, Hernandez-Ibanez et al teach that lactate is an essential metabolite present in embryonic cell culture. Changes of this important metabolite during the growth of human embryo reflect the quality and viability of the embryo. Hernandez-Ibanez et al teach a sensitive, stable, and easily manufactured electrochemical biosensor for the detection of lactate within embryonic cell culture media where screen-printed disposable electrodes are used as electrochemical sensing platforms for the miniaturization of the lactate biosensor (see for example, the abstract at page 1168).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the combined references before the effective filing date of the invention. The artisan would have been motivated to make and use the invention of Perozziello et al to enable research and enjoy the considerable technical and economic potential in the assisted reproductive technology for human beings as taught by Perozziello et al (see for example, the conclusion section at page 658) where inclusion of a processor reader would have been obvious to enable ease of observing the measurement and or control of the embryo-culture environment based upon measurements of stress variables such as pH (see for example, page 656 of Perozziello et al teaching that it is anticipated that the cells in the system are exposed to minimized physical stress and that metabolic waste products can be continuously removed due to the dynamic flow conditions; and paragraph 2 of the background at column 1 of Klein et al). The system of Klein is taught to be valuable for culturing mammalian cells (see for example, column 1 of Klein et al) such that the artisan would have expected to system of Klein et al to be compatible for adaptation according to the teachings of Perozziello et al. The resulting system reads upon and makes obvious the instantly claimed system for measuring pH of an embryo in in vitro culture. Where Hernandez-Ibanez et al teach the importance of measuring lactate in embryonic cell culture, the artisan would have found it obvious to modify the system of Perozziello et al and Klein et al to further comprise a sensor for measuring lactate (such as the sensor of Hernandez-Ibanez et al or an art-known equivalent). The artisan would have understood that the system of Klein, placing a sensor at the bottom of each well) allows for clear and relatively uncontaminated data collection for each, individual embryo while connection of the sensor to a computer/processor with a monitor allowing for continuous logging and monitoring of data, creates convenient ease of data access and allows for trends to be observed by the artisan. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Claim(s) 12-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Perozziello et al and Klein et al, as applied to claims 1-2, 4, 8-9, 20-22, and 24 above, in view of Seino et al (Fertility and Sterility, Volume 77, Issue 6, 2002, Pages 1184-1190, ISSN 0015-0282; https://doi.org/10.1016/S0015-0282(02)03103-5).
Regarding claims 12-13, Perozziello et al and Klein et al teach as set forth above.
Perozziello et al and Klein et al do not teach sensors or measurement of 8-OHdG as an oxidative stress marker.
However, Seino et al teach that eight-hydroxy-2′-deoxyguanosine (8-OHdG) is a sensitive indicator of DNA damage as the result of oxidative stress. To determine the effects of oxidative stress on the quality of oocytes and embryos, 8-hydroxy-2′-deoxyguanosine (8-OHdG) in granulosa cells was quantitatively studied during an in vitro fertilization and embryo transfer (IVF-ET) program. Seino et al found that oxidative stress in granulosa cells lowered fertilization rates and subsequently led to a decrease in the quality of embryos. 8-OHdG was measured by immunofluorescence (see for example, the abstract at page 1184, and pages 1185-11856). The use of immunofluorescence is deemed to read upon a sensor as instantly recited
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the combined references before the effective filing date of the invention. The artisan would have been motivated to make/arrange the system as claimed, including measurement/means for measuring 8-OHdG in embryo culture because Seino et l teach that 8-OHdG is a common measure of oxidative stress and that embryos with higher oxidative stress had lower implantation rates and were of lower quality, motivating the artisan to measure 8-OGdG and select for embryos with lower levels as associated with fewer issues with respect to implantation and quality. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Applicant’s Arguments and Reponses:
A. Applicant argues for withdrawal of the rejection of claim 21 under 35 USC §112(d) (see page 9 of the 07/06/2026 remarks)
Response: This is unpersuasive. The claims amendments dated 07/06/2026 do not recite a further limitation because the amendment that the instructions are written materials does not make the recitation a limitation which further limits and is not responsive to the rejection of record. Applicant points to In re Ngai, which affirms that, where the printed matter in no way depends on the kit, and the kit does not depend on the printed matter, printed material does not lend patentable weight. If such printed material were held to lend patentable weight, anyone could continue patenting a product indefinitely provided that they add a new instruction sheet to the product. (see In re Ngai 367 F.3d 1336 (Fed. Cir. 2004)). Therefore, the rejection as presented in this Office Action is maintained at this time.
B. Applicant argues for withdrawal of the rejections of the claims for obviousness over the cited references because the references allegedly only teach measurement of the pH of the embryo via measurement of the pH of the culture media (see pages 9-12 of the 07/06/2026 remarks).
Response: In response to Applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., precluding measurement of the pH of the embryo by measurement of the culture media) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). It is further noted that Applicant only describes, so as to convey possession at the time of filing, a sensor positioned at the bottom of the reservoir for culturing an embryo, said sensor measuring external pH of the embryo by measurement of the culture media (see for example, paragraph 0018 at page 3, paragraph 0024 at page 4 (detailing figures 3A-3B), paragraph 0047 at page 10, paragraph 0052 at page 11, paragraph 0081 at page 20, page 22, and paragraph 0089 at page 26 of the instant specification).
Additionally, as noted above, regarding the recited sensor reader configured to determine one or more variables about the embryo, the recitation covers any means for said configured sensor reader, including the means disclosed by the prior art (the reader/display of Perozziello et al). Therefore, the cited prior art reads upon an encompassed embodiment of the amended claim matter, being sufficient to make obvious the claims as amended (see the rejection of the claims under 35 USC §112(f) and its accompanying claim interpretation, set forth above).
Therefore, the rejections of the claim scope as described and presently drafted supports maintenance of the rejections for obviousness over the cited prior art as presented in the rejections under 35 USC §103 in this Office Action.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Gardner et al (Bioessays. 2015 Apr;37(4):364-71. doi: 10.1002/bies.201400155. Epub 2015 Jan 23) teach that the mammalian blastocyst exhibits a high capacity for aerobic glycolysis, a metabolic characteristic of tumours. Lactate creates a microenvironment of low pH around the embryo to assist the disaggregation of uterine tissues to facilitate trophoblast invasion. Further it is proposed that lactate acts as a signalling molecule (especially at the reduced oxygen tension present at implantation) to elicit bioactive VEGF recruitment from uterine cells, to promote angiogenesis. Finally it is suggested that the region of high lactate/low pH created by the blastocyst modulates the activity of the local immune response, helping to create immune tolerance. Consequently, the mammalian blastocyst offers a model to study the role of microenvironments, and how metabolites and pH are used in signalling.
The references cited on the 12/03/2024 IDS are deemed relevant.
Belli et al ((2019) “Oxygen Concentration Alters Mitochondrial Structure and Function in In Vitro Fertilized Preimplantation Mouse Embryos.” Human Reproduction, Vol. 34, No. 4, pp. 601-61; citation 3 under NPL on the 06/20/2023 IDS) and Maruyama ((2008) “On-chip pH Measurement Using Functionalized Gel-Microbeads Positioned by Optical Tweezers.” Lab on a Chip, Vol. 8, No. 2, pp. 346-351; citation 11 under NPL on the 06/20/2023 IDS) are deemed relevant.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/Ashley Gao/
Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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