DETAILED ACTION
Notice of 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 .
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 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.
Withdrawal of Objections and Rejections
Applicant's response, filed 07/08/2026, has been fully considered.
In view of the amendment and remarks, the objection to the specification and the rejection of the following claims are withdrawn:
claims 53 and 55 under 35 USC § 102.
The following rejections and/or objections are either maintained or newly applied for claims 53 and 55. They constitute the complete set applied to the instant application. Herein, "the previous Office action" refers to the Non-Final Rejection of 04/06/2026.
Status of the Claims
Claims 1-27, 29, 31-32, 36, 38, 41-42, 44-45 and 47-52 are canceled.
Claims 28, 30, 33-35, 37, 39-40, 43, 46 and 53-61 are pending.
Claims 28, 30, 33-35, 37, 39-40, 43, 46, 54 and 56-61 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention and species, as set forth in the Non-Final Office Action dated 04/06/2026. (See explanation in the Election/Restrictions section above).
Claims 53 and 55 are rejected.
Priority
This application US 18/026,058 (03/13/2023) is a 371 of PCT/US2021/050245 (09/14/2021) and claims priority from US Application 63/077,828 (09/14/2020), as reflected in the filing receipt mailed on 07/11/2023. However, the provisional application does not provide support for "method of screening for a therapeutic agent in breast tissue sample" as recited in claims 53 and 55. Therefore, the effective filing date of claims 53 and 55 is 09/14/2021.
Information Disclosure Statement
The information disclosure statement filed 08/14/2026 fails to comply with the provisions of 37 CFR 1.98(a)(4) because it lacks the appropriate size fee assertion. It has been placed in the application file, but the information referred to therein has not been considered as to the merits.
Specification Objections
The amendments to the specification submitted 07/08/2026 are accepted.
Claim objections
Claim 53 is objected to because of the following informality: the recited “determining using RNA sequencing an increased gene expression level” should read “determining, using RNA sequencing, an increased gene expression level” for proper grammar. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 53 and 55 are rejected under 35 USC § 101 because the claimed inventions are directed to one or more Judicial Exceptions (JEs) without significantly more. Regarding JEs, "Claims directed to nothing more than abstract ideas..., natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 §I). Abstract ideas include mathematical concepts and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)). Any newly recited portions are necessitated by claim amendment.
101 background
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below. MPEP 2106 and the following USPTO website provide further explanation and case law citations: uspto.gov/patent/laws-and-regulations/examination-policy/examination-guidance-and-training-materials.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter (MPEP 2106.03)?
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Analysis of instant claims
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The instant claims are directed to a method (claims 53 and 55) which falls within one of the categories of statutory subject matter.
[Step 1: claims 53 and 55: Yes]
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Background
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships
and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
Analysis of instant claims
With respect to the instant claims, under the Step 2A, Prong One evaluation, the claims are found to recite abstract ideas that fall into the grouping of mental processes (in particular procedures for observing, analyzing and organizing information) and mathematical concepts (in particular mathematical relationships and formulas) as well as a law of nature or a natural phenomenon are as follows:
• " b) determining whether the cell or the population of cells migrates through the migratory channel of the apparatus and to the bifurcation point of the channel in the presence and absence of the therapeutic agent" (independent claim 53)
• "c) determining … an increased gene expression level of one or more of DUSP5, PLK3, PPP1R15A, FOSL1, CDKN1A, KLF6, VDR, ARL4C, ADM, PLAU, VEGFA, NQO1, HMOX1, PGK1, LITAF, HPCAL1 and FTH1 in the cell or the population of cells in step b) compared to a predetermined reference level of gene expression of DUSP5, PLK3, PPP1R15A, FOSL1, CDKN1A, KLF6, VDR, ARL4C, ADM, PLAU, VEGFA, NQO1, HMOX1, PGK1, LITAF, HPCAL1 and FTH1" (independent claim 53) and
• "d) determining that the therapeutic agent is an inhibitor of cancer cell migration when the cell or population of cells does not migrate through the migratory channel of the apparatus and to the bifurcation point of the channel in the presence of the therapeutic agent" (independent claim 53).
The abstract ideas recited in the claims are evaluated under the Broadest Reasonable Interpretation (BRI) and determined to each cover performance either in the mind and/or by mathematical operation. Without further detail as to the methodology involved in "determining a therapeutic agent as an inhibitor" depending on "determining whether the cell or the population of cells migrates through the migratory channel of the apparatus and to the bifurcation point of the channel in the presence and absence of the therapeutic agent", under the BRI, one may simply, evaluate the cell migration using data observed. The human mind is also sufficiently capable of evaluate information based on observation and judgment. (MPEP 2106.04(a)(2)(III)) pertains.
The instant claims also recite a natural correlation by correlating the relationship between naturally derived cells and their natural response to agents. (see MPEP 2106.04(b).I).
[Step 2A Prong One: claims 53 and 55: Yes ]
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Background
MPEP 2106.04(d).I lists the following example considerations for evaluating whether a judicial exception is integrated into a practical application:
An improvement in the functioning of a computer or an improvement to other technology or another technical field, as discussed in MPEP §§ 2106.04(d)(1) and 2106.05(a);
Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition, as discussed in MPEP § 2106.04(d)(2);
Implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b);
Effecting a transformation or reduction of a particular article to a different state or thing, as discussed in MPEP § 2106.05(c); and
Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception, as discussed in MPEP § 2106.05(e).
Analysis of instant claims
Instant claim 53 recites additional elements that are not abstract ideas:
• "a) placing a cell or a population of cells from a brain or breast tissue sample in an integrative microfluidic apparatus, wherein the integrative microfluidic apparatus comprises a migratory channel and a bifurcation point in the channel" (independent claim 53) and
• "c) …using RNA sequencing …" (independent claim 53).
Claim 55 further limits the breast tissue sample to being from a subject diagnosed with breast cancer.
Considerations under Step 2A, Prong Two
The recited "a) placing a cell or a population of cells from a brain or breast tissue sample in an integrative microfluidic apparatus, wherein the integrative microfluidic apparatus comprises a migratory channel and a bifurcation point in the channel" and "c) … using RNA sequencing …" reads on physical steps which constitutes data gathering activities; because the recited step constitutes in placing cells in a device for further data evaluation by the judicial exception; not amounting to a practical application. Therefore, the recited is an insignificant extra-solution activity since this limitation serve to gather data that is utilized as input for the judicial exception. See MPEP 2106.05(g) and MPEP 2106.04(d).
In Step 2A, Prong One above, claim steps and/or elements were identified as part of one or more judicial exceptions (JEs).
In this Step 2A, Prong Two immediately above claim steps and/or elements were identified as part of one or more additional elements. Additional elements are further discussed in Step 2B below.
Here in Step 2A, Prong Two, no additional step or element clearly demonstrates integration of the JE(s) into a practical application.
[Step 2A Prong Two: claims 53 and 55: No]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
According to analysis so far, the additional elements described above do not provide significantly more than the judicial exception. A determination of whether additional elements provide significantly more also rests on whether the additional elements or a combination of elements represents other than what is well-understood, routine, and conventional. Conventionality is a question of fact and may be evidenced as: a citation to an express statement in the specification or to a statement made by an applicant during examination that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to the instant claims, the prior art review to Murphy ("Recent advances in the use of microfluidic technologies for single cell analysis." Analyst 143.1:60-80 (2017) – newly cited) discloses the use of microfluidic platform for the analysis of cell migration to understanding invasive and malignant diseases such as cancer (pg. 66 col. 1 para. 2) and the use of microfluidic droplet-based RNA-seq devices for the detection of genetic material in human cancer cell lines (pg. 71 col. 2 para. 2) are routine, well-understood and conventional in the art.
When the claims are considered as a whole, they do not integrate the abstract idea into a practical application; they do not confine the use of the abstract idea to a particular technology; they do not solve a problem rooted in or arising from the use of a particular technology; they do not improve a technology by allowing the technology to perform a function that it previously was not capable of performing; and they do not provide any limitations beyond generally linking the use of the abstract idea to a broad technological environment. See MPEP 2106.05(a) and 2106.05(h).
The instant claims constitute insignificant extra solution activity, and when considered individually, are insufficient to constitute inventive concepts that would render the claims significantly more than an abstract idea (see MPEP 2106.05(g)). Hence, these elements, when considered individually, are insufficient to constitute inventive concepts that would render the claims significantly more than an abstract idea (see MPEP 2106.05(d)).
[Step 2B: claims 53 and 55: No]
Conclusion: Instant claims are directed to non-statutory subject matter
For the reasons above, the claims in this instant application, when the limitations are considered individually and as a whole, are directed to an abstract idea and lack an inventive concept not clearly anything significantly more.
Response to applicant's remarks in regard to Claim Rejection 35 U.S.C. ~ 101
The Remarks of 07/08/2026 have been fully considered but are not persuasive for the reasons below:
Applicant asserts starting in pg. 9 para. 1:
The U.S. Supreme Court has provided a two-step test for determining patent eligibility under 35 U.S.C. § 101. Step 1 asks, "Is the claim to a process, machine, manufacture or composition of matter?" Using the claims of the instant application, the answer to Step 1 is yes, claim 53 are directed to processes (i.e., a method of screening for a therapeutic agent). Because the answer to Step 1 is yes, Step 2A is then addressed. Step 2A asks, "Is the claim directed to a law of nature, a natural phenomenon, or an abstract idea?" Applicant submits that the answer to Step 2A is no; claim 53 is not directed to a law of nature, a natural phenomenon, or an abstract idea. Even if the answer to Step 2A is Y.§, the analysis must move to Step 2B, where claim 53 must be analyzed to determine whether it is directed to any judicial exception. Claim 53, when analyzed as a whole, is not directed to any judicial exception
It is respectfully submitted that this is not persuasive because the argued analysis of the recited claims under 35 USC 101 is misapplied. With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as: mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations) (MPEP 2106.04(a)(2)(I)); certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)). If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d)) under Step 2A Prong Two. The analysis at Step 2A, Prong 2, considers the claims as a whole, i.e., the additional elements in combination with the judicial exceptions (see MPEP 2106.05(a)), although the integration or improvement provided in the claim must flow from the additional elements and not the judicial exceptions to be considered persuasive. However, Step 2B instructs that an inventive concept cannot be provided the by judicial exception. An “inventive concept” is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself (Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966)). Therefore, there are no judicial exceptions considerations under Step 2B.
Applicant asserts starting in pg. 9 para. 2:
Specifically, Applicant submits that independent claim 53, as a whole, are not directed to a recognized exception, and is patent eligible … Thus, it appears that the analysis of the pending claims already proceeded to Step 2B. …the answer to Step 2B is YES because claim 53, taken as a whole, recites elements or combination of elements that are sufficient to ensure the claim amounts to significantly more than the exception. The Abstract Ideas Examples supports Applicant's position as they provide guidance on examples of when specific steps or acts recited in a claim under Step 2B, amount to significantly more than the exception
It is respectfully submitted that this is not persuasive because the claims as a whole, considering all claim elements both individually and in combination, do not amount to significantly more than the abstract idea and the identified additional element do not provide sufficient evidence to ensure that the claim as a whole amounts to significantly more than the judicial exception itself. Step 2B instructs that an inventive concept cannot be provided the by judicial exception – which includes abstract ideas - but must be provided by an additional element – which is not the case here. An “inventive concept” is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself (Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966)). In this instant case, the identified additional elements are shown to be well-understood, routine, conventional activities previously known to the industry.
Applicant asserts starting in pg. 10 para. 2:
Applicant submits that amended claim 53, as a whole, when analyzed to determine whether any additional element or combination of elements, amounts to significantly more than the alleged exception to patentability. As in the Abstract Ideas Example 39, while some of the recited elements of claim 53 may be based on mathematical concepts, the claim does not recite any mathematical relationships, formulas, or calculations, claim 53, as amended herein, recites steps when viewed as a combination do not recite any of the judicial exceptions. For instance, claim 53 as amended herein now recites "determining using RNA sequencing an increased gene expression level of one or more of DUSP5, PLK3, PPP IRI 5A, FOSLI, CD KN IA, KLF6, VDR, ARL4C, ADM, PLAU, VEGFA, NQOI, HMOXI, PGKI, LITAF, HPCALI and FTHI in the cell or the population of cells in step b) compared to a predetermined reference level of gene expression of DUSP5, PLK3, PPPIRl5A, FOSLI, CDKNIA, KLF6, VDR, ARL4C, ADM, PLAU, VEGFA, NQOI, HMOXI, PGKI, LITAF, HPCALI and FTHI" in new step c); (emphasis added)- a step that does not require a mental process because this step is not practically performed in the human mind.
It is respectfully submitted that this is not persuasive because the instantly claimed invention is not analogous to Example 39. Example 39 considers a hypothetical method for training a neural network for facial detection. The exemplified claim comprises modifying a set of digital facial images by performing digital transformation steps (e.g., smoothing and contrast reduction) and training a neural network in two stages using unmodified facial images, modified facial images, and non-facial images. The Examiner agrees with the statement provided in the Guidance that “the claim does not recite a mental process because the steps are not practically performed in the human mind” (pg. 9 of ‘Subject Matter Eligibility Examples: Abstract Ideas’). However, the Examiner considers the exemplified process as non-analogous to that recited by the instant claims the claimed invention is directed to screening for a therapeutic agent and there are no integration of judicial elements into a practical application realized by any additional element.
Applicant asserts starting in pg. 11 para. 2:
As related to step 2B, Applicant again respectfully submits that technical improvements as related to additional elements satisfy eligibility requirements as integrated to the process as a whole and providing a concrete improvement in the technical context. The claims require the use of RNA sequencing of a gene panel yielding multiple gene expression levels per cell or population of cells which allows for the determination of identifying a therapeutic agent that is capable of inhibiting migration of a cancer cell but also useful in treating a subject with breast cancer that has an increased risk of short survival or recurrence of breast cancer (see, for example, Example 2 of the published application). At least this attribute is an example of the associated improvement over the prior art and confer patent eligibility. Regardless, the presently amended claims include additional method steps to capture features related to at least a specific analysis, and improvements. That is, measuring an increased gene expression of one or more of DUSP5, PLK3, PPP IRI 5A, FOSLI, CDKNIA, KLF6, VDR, ARL4C, ADM, PLAU, VEGFA, NQOI, HMOXI, PGKI, LITAF, HPCALI and FTHI using RNA sequencing of the cell or the population of cells migrates through the migratory channel of the apparatus and to the bifurcation point of the channel in the presence and absence of the therapeutic agent provides for integration and presentation for practical application in a manner improving the technical field.
It is respectfully submitted that this is not persuasive the Applicant appears to be conflating the two steps: "significantly more" at Step 2B findings with searches for a practical application at step 2A, Prong 2.
The analysis at Step 2A, Prong 2, considers the claims as a whole, i.e., the additional elements in combination with the judicial exceptions (see MPEP 2106.05(a)), although the integration or improvement provided in the claim must flow from the additional elements and not the judicial exceptions to be considered persuasive. However, Step 2B instructs that an inventive concept cannot be provided the by judicial exception. An “inventive concept” is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself (Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966)). The limitations regarding “measuring an increased gene expression” pointed by the Applicant are considered to recite a judicial exception (i.e. "c) determining … an increased gene expression level of one or more of DUSP5, PLK3, PPP1R15A, FOSL1, CDKN1A, KLF6, VDR, ARL4C, ADM, PLAU, VEGFA, NQO1, HMOX1, PGK1, LITAF, HPCAL1 and FTH1 in the cell or the population of cells in step b) compared to a predetermined reference level of gene expression of DUSP5, PLK3, PPP1R15A, FOSL1, CDKN1A, KLF6, VDR, ARL4C, ADM, PLAU, VEGFA, NQO1, HMOX1, PGK1, LITAF, HPCAL1 and FTH1" - independent claim 53) as described above and are therefore not considered at Step 2B.
Applicant asserts starting in pg. 11 para. 6:
Applicant submits that independent claim 53 is directed to specific active steps of placing a cell or a population of cells from a brain or breast tissue sample in an integrative microfluidic apparatus, wherein the integrative microfluidic apparatus comprises a migratory channel and a bifurcation point in the channel; determining whether the cell or the population of cells migrates through the migratory channel of the apparatus and to the bifurcation point of the channel in the presence and absence of the therapeutic agent; and determining using RNA sequencing an increased gene expression level of one or more of DUSP5, PLK3, PPPIRl5A, FOSLI, CDKNIA, KLF6, VDR, ARL4C, ADM, PLAU, VEGFA, NQOI, HMOXI, PGKI, LITAF, HPCALI and FTH I in the cell or the population of cells in step b) compared to a predetermined reference level of gene expression of DUSP5, PLK3, PPP IRI 5A, FOSLI, CD KN IA, KLF6, VDR, ARL4C, ADM, PLAU, VEGFA, NQOI, HMOXI, PGKI, LITAF, HPCALI and FTHI and is not directed to a law of nature, a natural phenomenon, or an abstract idea. The Office Action alleges that the claims are not integrated into a practical application because they allegedly provide only "insignificant extra-solution activity". Applicant respectfully disagrees. Claim 53 does not merely insignificant extra-solution activities. Instead, claim 53 recites "placing a cell or a population of cells from a brain or breast tissue sample in an integrative microfluidic apparatus, wherein the integrative microfluidic apparatus comprises a migratory channel and a bifurcation point in the channel; and determining whether the cell or the population of cells migrates through the migratory channel of the apparatus and to the bifurcation point of the channel in the presence and absence of the therapeutic agent" These limitation are an active, physical, wet-laboratory step that creates a physical means for cells to either migrate through or to be prevented from migrating through in the presence of an exogenously added therapeutic agent.
It is respectfully submitted that this is not persuasive because the argued “specific active steps of placing a cell or a population of cells from a brain or breast tissue sample in an integrative microfluidic apparatus” is indeed an active, physical, wet-laboratory step that creates a physical means; however said step have been identified as a data gathering activity and thus insignificant extra-solution activities at step 2A Prong 2. The argued “placing” step have also been examined at step 2B which have been shown to be to be well-understood, routine, conventional activities previously known to the industry. The argued “determining” steps have all been previously examined and identified as judicial exceptions – see Claim Rejections above.
Applicant asserts starting in pg. 13 para. 2:
Independent claim 53, and dependent claim 55, are also patent eligible at least because they provide an improvement to a technology. The claims recite placing a cell or a population of cells from a brain or breast tissue sample in an integrative microfluidic apparatus, wherein the integrative microfluidic apparatus comprises a migratory channel and a bifurcation point in the channel; determining whether the cell or the population of cells migrates through the migratory channel of the apparatus and to the bifurcation point of the channel in the presence and absence of the therapeutic agent; and determining using RNA sequencing an increased gene expression level of one or more of DUSP5, PLK3, PPP IRI 5A, FOSLI, CDKNIA, KLF6, VDR, ARL4C, ADM, PLAU, VEGFA, NQOI, HMOXI, PGKI, LITAF, HPCALI and FTH I in the cell or the population of cells in step b) compared to a predetermined reference level of gene expression of DUSP5, PLK3, PPP IRl5A, FOSLI, CDKNIA, KLF6, VDR, ARL4C, ADM, PLAU, VEGFA, NQOI, HMOXI, PGKI, LITAF, HPCALI and FTHI, which provides both a physical and genetic assay which is different than the assay described in Yankaska. As described in the 2019 Patent Eligibility Guidelines and consistent with the ruling of the Court in Alice Corp. v. CLS Bank International, an improvement to a technology or a technical field is patent eligible. See October 2019 Patent Eligibly Guidance Update at pp. 11-13; Alice Corp. v. CLS Bank International, 134 S. Ct. 2347 at 2358 (2014) (citing Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 US. 132 S.Ct. 1289, 1299, 182 L.Ed2d 321 (2012); and Diamond v. Diehr, 450 US. 175, 187, IOI S.Ct. 1048, 67 L.Ed2d 155 (1981)). Thus, the current claims allow an improved screening as for identifying therapeutic agents for metastatic breast or brain cancer with associated with reduced overall survival and multiple advantages, over the current state of the art, in assessing breast or brain cancer cells for changes gene expression or their migratory ability
It is respectfully submitted that this is not persuasive because there is no improvement to a technology being provided by the one identified additional element at Step 2A Prong 2. The step of “placing a cell or a population of cells from a brain or breast tissue sample in an integrative microfluidic apparatus” is not sufficient to provide an improvement to a technology because it reads on data gathering activities in the process of screening for a therapeutic agent. The Applicant appears to argue that the improvement is in screening for therapeutic agents in assessing breast or brain cancer cells for changes gene expression or their migratory ability, but the instant claims does not associate the gene expression levels with any cancer as claimed nor with the screening of said agents. Therefore, said arguments about improvement are also not commensurate in scope
Applicant asserts starting in pg. 14 para. 3:
The 2019 PEG recognizes that claims are not "directed to" an abstract idea when they apply an alleged exception "with, or by use of, a particular machine" and/or effect a transformation of a particular article to a different state, which is the type of practical application the Supreme Court endorsed in Diehr (Diamond v. Diehr, 450 U.S. 175 (1981)). See Diehr (claims must be considered "as a whole" and are eligible when the process effects a transformation). Applicant submits in the claimed methods that the a cell or a population of cells from a brain or breast tissue sample (claim 53) are placed in an integrative microfluidic apparatus in the presence of a therapeutic agent and that RNA sequencing is used to determine whether the cell or population of cells has an increased gene level of one or more of DUSP5, PLK3, PPPIRl5A, FOSLI, CDKNIA,KLF6, VDR,ARL4C,ADM,PLAU, VEGFA, NQO1, HMOXI, PGKI, LITAF, HPCALI and FTHI. Thus, a cell or a population of cells from a brain or breast tissue sample is transformed by converting the gene expression into a value that indicates the overall survival in the breast or brain cell before exposure to the therapeutic agent and assessment of whether the cell or population of cells from a brain or breast tissue sample migrates through the migratory channel of the apparatus and to the bifurcation point of the channel in the presence and absence of the therapeutic agent. Thus, the physical characteristics of the cell or population of cells from a brain or breast tissue sample have been transformed by the applying RNA sequencing.
It is respectfully submitted that this is not persuasive because the argued transformation in “a cell or a population of cells from a brain or breast tissue sample is transformed by converting the gene expression into a value” is not in agreement with the listed transformation consideration for evaluating whether a judicial exception is integrated into a practical application in MPEP 2106.04(d). MPEP § 2106.05(c) instructs that a judicial exception is integrated into a practical application when the claims effect a transformation or reduction of a particular article to a different state or thing and “For data, mere "manipulation of basic mathematical constructs [i.e. cells from a brain or breast tissue sample is transformed by converting the gene expression into a value] the paradigmatic ‘abstract idea,’" has not been deemed a transformation.”, which indicates that transforming something physical into data isn’t a meaningful or particular transformation.
Regarding the arguments related to "particular machine," it is respectfully submitted that this is not persuasive because, while MPEP 2106.05(b) does set forth that the application of a judicial exception with, or by use of, a particular machine may integrate a judicial exception into a practical application in Step 2A Prong 2 or recite significantly more than a judicial exception in Step 2B, this requires that the particular machine apply the judicial exception. There is no evidence in the claims of a particular machine – hence, no required special architecture neither changes the functioning of a computer – that performs said integration of judicial exception into a practical application in Step 2A Prong 2 or recite significantly more than a judicial exception in Step 2B. MPEP 2106.05(b)(III) sets forth that if the use of a machine contributes only nominally or insignificantly to the execution of the claimed method, it would not integrate a judicial exception or provide significantly more.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 53 and 55 are rejected under 35 U.S.C. 103(a) as being unpatentable over Yankaska ("A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens." Nature biomedical engineering 3(6)452-465 (2019) – cited on the 04/06/26 892 PTO Form) in view of Yuan ("An automated microwell platform for large-scale single cell RNA-seq." Scientific reports 6.1:33883 (2016) – newly cited). Any newly recited portions are necessitated by claim amendment.
Claim 53 recites
a) placing a cell or a population of cells from a brain or breast tissue sample in an integrative microfluidic apparatus, wherein the integrative microfluidic apparatus comprises a migratory channel and a bifurcation point in the channel;
b) determining whether the cell or the population of cells migrates through the migratory channel of the apparatus and to the bifurcation point of the channel in the presence and absence of the therapeutic agent; …
d) determining that the therapeutic agent is an inhibitor of cancer cell migration when the cell or population of cells does not migrate through the migratory channel of the apparatus and to the bifurcation point of the channel in the presence of the therapeutic agent
• Yankaska teaches the development and testing of a microfluidic assay that quantifies the abundance and proliferative index of migratory cells in breast-cancer specimens (pg. 452 para. 1) named Microfluidic Assay for quantification of Cell Invasion (MAqCI) (pg. 453 col. 1 para. 1); wherein cells that reach the far end of the feeder channel encounter a bifurcation region and must choose between two narrower branch channels (i.e. a) placing a cell or a population of cells from a brain or breast tissue sample in an integrative microfluidic apparatus, wherein the integrative microfluidic apparatus comprises a migratory channel and a bifurcation point in the channel) (pg. 453 col. 1 para. 1); wherein MAqCI is capable of identifying highly migratory and proliferative cells that have enhanced metastatic potential in response to a specific therapeutic regimen (i.e. (b) determination of whether the cell or the population of cells migrates through the migratory channel of the apparatus and to the bifurcation point of the channel in the presence and absence of the therapeutic agent) (pg. 459 col. 1 para. 3); wherein MAqCI is used to test therapeutic agents from ongoing clinical trials (pg. 460 Fig. 6); showing inhibition of cell migration for cells during treatment when compared to vehicle control (i.e. (d) determining that the therapeutic agent is an inhibitor of cancer cell migration when the cell or population of cells does not migrate through the migratory channel of the apparatus and to the bifurcation point of the channel in the presence of the therapeutic agent) (pg. 460 Fig. 6A)
c) determining using RNA sequencing an increased gene expression level of one or more of DUSP5, PLK3, PPPR15A, FOSL1, CDKNIA, KLF6, VDR, ARL4C, ADM, PLA U, VEGFA, NOOJ, HMOXI, PGKI, LITAF, HPCAL1 and FTH1 in the cell or the population of cells in step b) compared to a predetermined reference level of gene expression of DUSP5, PLK3, PPP1R15A, FOSL1, CDKN1A, KLF6, VDR, ARL4C, ADM, PLAU, VEGFA, NQO1, HMOX1, PGK1, LITAF, HPCAL1 and FTH1; and
• Yankaska does not teach the recitation above. However, Yuan teaches an automated microwell array platform for single cell RNA-Seq to assess heterogeneity in gene expression of patient-derived glioma (pg. 1 Abstract); wherein genetic subtypes clustering analysis included the ARL4C gene (SI pg. 7 Table 2 and main text pg. 6 Fig. 4).
Claim 55 recites
wherein breast tissue sample is from a subject diagnosed with breast cancer
• Yankaska teaches the development and testing of a microfluidic assay that quantifies the abundance and proliferative index of migratory cells in breast-cancer specimens (pg. 452 para. 1).
Rationale for combining (MPEP §2142-2143)
Regarding claims 53 and 55, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Yankaska in view of Yuan because all references disclose the use of microfluidic platform for expression profiling of cancer cells. The motivation would have been to develop microfluidic tools for genome-wide analysis of individual cells and analyze thousands of individual cells from complex tissues (pg. 6 para. 4 Yuan).
Therefore it would have been obvious to one of ordinary skill in the art to substitute the use of microfluidic platform for expression profiling of cancer cells of Yankaska to the methods by Yuan because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to the use of microfluidic platform for expression profiling of cancer cells.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the "right to exclude" granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
A. Claims 53 and 55 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16, 19 and 28 of US Patent No 12493037 in view of Yankaska ("A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens." Nature biomedical engineering 3(6)452-465 (2019) – cited on the 04/06/26 892 PTO Form) in view of Yuan ("An automated microwell platform for large-scale single cell RNA-seq." Scientific reports 6.1:33883 (2016) – newly cited).
• US Patent No 12493037 teaches claim 53 except the "determining cells migration in the presence or absence of a therapeutic agent", step (c) and the limitations of claim 55.
However, Yankaska teaches the "determining cells migration in the presence or absence of a therapeutic agent" as the development and testing of a microfluidic assay that quantifies the abundance and proliferative index of migratory cells in breast-cancer specimens (pg. 452 para. 1) named Microfluidic Assay for quantification of Cell Invasion (MAqCI) (pg. 453 col. 1 para. 1); wherein cells that reach the far end of the feeder channel encounter a bifurcation region and must choose between two narrower branch channels (pg. 453 col. 1 para. 1); wherein MAqCI is capable of identifying highly migratory and proliferative cells that have enhanced metastatic potential in response to a specific therapeutic regimen (pg. 459 col. 1 para. 3); wherein MAqCI is used to test therapeutic agents from ongoing clinical trials (pg. 460 Fig. 6); showing inhibition of cell migration for cells during treatment when compared to vehicle control (pg. 460 Fig. 6A).
Furthermore, Yuan teaches step (c) as an automated microwell array platform for single cell RNA-Seq to assess heterogeneity in gene expression of patient-derived glioma (pg. 1 Abstract); wherein genetic subtypes clustering analysis included the ARL4C gene (SI pg. 7 Table 2 and main text pg. 6 Fig. 4).
Additionally, Yankaska teaches claim 55 as the development and testing of a microfluidic assay that quantifies the abundance and proliferative index of migratory cells in breast-cancer specimens (i.e. wherein breast tissue sample is from a subject diagnosed with breast cancer) (pg. 452 para. 1).
Rationale for combining (MPEP §2142-2143)
Regarding claims 53 and 55, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of US Patent No 12493037 in view of Yankaska and Yuan because all references disclose methods for the investigation of cancer cells migratory properties. The motivation would have been to incorporate a method aiming the selection of effective therapeutic regimens (pg. 452 para. 1 Yankaska) and to develop microfluidic tools for genome-wide analysis of individual cells and analyze thousands of individual cells from complex tissues (pg. 6 para. 4 Yuan).
Therefore it would have been obvious to one of ordinary skill in the art to substitute the investigation of cancer cells migratory properties of US Patent No 12493037 to the methods by Yankaska and Yuan because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for the investigation of cancer cells migratory properties.
B. Claims 53 and 55 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of US Patent No. 11747338 in view of Yankaska ("A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens." Nature biomedical engineering 3(6)452-465 (2019) – cited on the 04/06/26 892 PTO Form) in view of Yuan ("An automated microwell platform for large-scale single cell RNA-seq." Scientific reports 6.1:33883 (2016) – newly cited).
• US Patent No. 11747338 teaches claim 53 except the "determining cells migration in the presence or absence of a therapeutic agent", step (c) and the limitations of claim 55.
However, Yankaska teaches the "determining cells migration in the presence or absence of a therapeutic agent" as the development and testing of a microfluidic assay that quantifies the abundance and proliferative index of migratory cells in breast-cancer specimens (pg. 452 para. 1) named Microfluidic Assay for quantification of Cell Invasion (MAqCI) (pg. 453 col. 1 para. 1); wherein cells that reach the far end of the feeder channel encounter a bifurcation region and must choose between two narrower branch channels (pg. 453 col. 1 para. 1); wherein MAqCI is capable of identifying highly migratory and proliferative cells that have enhanced metastatic potential in response to a specific therapeutic regimen (pg. 459 col. 1 para. 3); wherein MAqCI is used to test therapeutic agents from ongoing clinical trials (pg. 460 Fig. 6); showing inhibition of cell migration for cells during treatment when compared to vehicle control (pg. 460 Fig. 6A).
Furthermore, Yuan teaches step (c) as an automated microwell array platform for single cell RNA-Seq to assess heterogeneity in gene expression of patient-derived glioma (pg. 1 Abstract); wherein genetic subtypes clustering analysis included the ARL4C gene (SI pg. 7 Table 2 and main text pg. 6 Fig. 4).
Additionally, Yankaska teaches claim 55 as the development and testing of a microfluidic assay that quantifies the abundance and proliferative index of migratory cells in breast-cancer specimens (i.e. wherein breast tissue sample is from a subject diagnosed with breast cancer) (pg. 452 para. 1).
Rationale for combining (MPEP §2142-2143)
Regarding claims 53 and 55, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of US Patent No. 11747338 in view of Yankaska and Yuan because all references disclose methods for the investigation of cancer cells migratory properties. The motivation would have been to incorporate a method aiming the selection of effective therapeutic regimens (pg. 452 para. 1 Yankaska) and to develop microfluidic tools for genome-wide analysis of individual cells and analyze thousands of individual cells from complex tissues (pg. 6 para. 4 Yuan).
Therefore it would have been obvious to one of ordinary skill in the art to substitute the investigation of cancer cells migratory properties of US Patent No. 11747338 to the methods by Yankaska and Yuan because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for the investigation of cancer cells migratory properties.
C. Claims 53 and 55 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of US Patent No. 11559803 in view of Yankaska ("A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens." Nature biomedical engineering 3(6)452-465 (2019) – cited on the 04/06/26 892 PTO Form) in view of Yuan ("An automated microwell platform for large-scale single cell RNA-seq." Scientific reports 6.1:33883 (2016) – newly cited).
• US Patent No. 11559803 teaches claim 53 except the "determining cells migration in the presence or absence of a therapeutic agent", step (c) and the limitations of claim 55.
However, Yankaska teaches the "determining cells migration in the presence or absence of a therapeutic agent" as the development and testing of a microfluidic assay that quantifies the abundance and proliferative index of migratory cells in breast-cancer specimens (pg. 452 para. 1) named Microfluidic Assay for quantification of Cell Invasion (MAqCI) (pg. 453 col. 1 para. 1); wherein cells that reach the far end of the feeder channel encounter a bifurcation region and must choose between two narrower branch channels (pg. 453 col. 1 para. 1); wherein MAqCI is capable of identifying highly migratory and proliferative cells that have enhanced metastatic potential in response to a specific therapeutic regimen (pg. 459 col. 1 para. 3); wherein MAqCI is used to test therapeutic agents from ongoing clinical trials (pg. 460 Fig. 6); showing inhibition of cell migration for cells during treatment when compared to vehicle control (pg. 460 Fig. 6A).
Furthermore, Yuan teaches step (c) as an automated microwell array platform for single cell RNA-Seq to assess heterogeneity in gene expression of patient-derived glioma (pg. 1 Abstract); wherein genetic subtypes clustering analysis included the ARL4C gene (SI pg. 7 Table 2 and main text pg. 6 Fig. 4).
Additionally, Yankaska teaches claim 55 as the development and testing of a microfluidic assay that quantifies the abundance and proliferative index of migratory cells in breast-cancer specimens (i.e. wherein breast tissue sample is from a subject diagnosed with breast cancer) (pg. 452 para. 1).
Rationale for combining (MPEP §2142-2143)
Regarding claims 53 and 55, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of US Patent No. in view of Yankaska and Yuan because all references disclose methods for the investigation of cancer cells migratory properties. The motivation would have been to incorporate a method aiming the selection of effective therapeutic regimens (pg. 452 para. 1 Yankaska) and to develop microfluidic tools for genome-wide analysis of individual cells and analyze thousands of individual cells from complex tissues (pg. 6 para. 4 Yuan).
Therefore it would have been obvious to one of ordinary skill in the art to substitute the investigation of cancer cells migratory properties of US Patent No. 11559803 to the methods by Yankaska and Yuan because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for the investigation of cancer cells migratory properties.
Conclusion
No claims are allowed.
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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/F.F.L./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
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