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 .
REQUEST FOR CONTINUED EXAMINATION
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/22/2025 has been entered.
Information Disclosure Statement
The IDS filed 11/21/2023, 6/13/2023, 2/01/2023, 12/27/2021, 11/02/2020, and 9/21/2020 have been considered by the Examiner.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Priority of US application 62/645,652 filed 3/20/2018 is acknowledged.
Status of Claims
The amendments filed 10/22/2025 are acknowledged.
Claims 1-3, 6, 8, 9, 11, 15, 17-20 and 22 are under examination.
Claims 4-5, 7, 10, 12-14, 16, 21, 23, 25, 26, 30-33 and 35-78 are cancelled.
Claims 24, 27-29 and 34 are withdrawn.
Claim Rejections - 35 USC § 101
The instant rejection is maintained from the Office Action filed 5/23/2025 and modified in view of Amendments filed 10/22/2025.
The following rejection is maintained but also modified in view of Applicant’s amendments filed 12/02/2024.
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 1-3, 6, 8, 9, 11, 15, 17-20 and 22 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
Step 1: Process, Machine, Manufacture or Composition
Claims 1-3, 6, 8, 9, 11, 15, 17-20 and 22 are drawn to a method, so a process.
Step 2A Prong One: Identification of an Abstract Idea
The claim(s) recite(s):
1. measuring one or more optical and fluidic force fluid-based parameters of biological cells or sub-cellular components or fractions using at least one analyzer comprising a laser force cytology analyzer, wherein the one or more optical fluid based parameters comprises the list of parameters in claim 1.
The instant limitation reads on a process that can be performed by the human mind or with math and is therefore an abstract idea. The claim requires measuring parameters with a laser force cytology analyzer. Under Broadest Reasonable Interpretation, the recited analyzer could read on an algorithm, software or a generic computer. See the 112(a) and 112(b) rejections below. The instant specification discloses an embodiment where measuring parameters is being performed by a generic computer (par. 0040) and an intelligent algorithm (par. 0041).
2. determining a response metric (RM) to describe the cellular response to one or more stimuli or analytes based on the one or more optical and fluidic force-based parameters, as in claim 1.
The step reads on a process that can be performed by the human mind or with math. Mental processes and math are abstract ideas.
2. measuring, using the laser force cytology analyzer, a cellular response to the one or more stimuli or analytes of at least one unknown sample.
This step generally reads on a mental process of measuring through data analysis and is therefore an abstract idea. The recited analyzer reads on a generic computer or generic algorithm which may be math or abstract idea steps of analyzing data.
3. Using the response metric (RM) to quantify the one or more stimuli or analytes to which the unknow sample was treated.
This step reads on a process of data analysis that can be performed by the human mind and is therefore an abstract idea.
4. determining the target value range of the RM based on differential cellular response to the varying amounts of the analyte or stimuli, as in claim 2.
The step reads on a process that can be performed by the human mind or with math. Mental processes and math are abstract ideas.
5. Analyzing cellular samples treated with varying unknow amounts of stimuli or analyte until an accurate measurement of the cellular response is determined, based on an RM that falls within a target value, as in claim 3.
The step of analyzing reads on a process that can be performed by the human mind or with math. Mental processes and math are abstract ideas.
6. comparing the response metric to an initial unknow sample, selecting a second unknown sample, comparing the response metric of the second unknown sample, and selecting subsequent unknown samples, as in claim 6.
The step reads on a processes that can be performed by the human mind or with math. Mental processes and math are abstract ideas.
Step 2A Prong Two: Consideration of Practical Application
The claims do not recite additional elements that integrate the abstract idea into a practical application. The claims recite receiving biological sample cells with varying amounts of stimuli or analyte. This step is part of an initial data gathering step and does not integrate the recite abstract idea steps into a practical application. Instead, the claims result in an analysis step of using the RM to quantify stimuli or analytes and thus the claims do not meet any of the following criteria:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
an additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
an additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
an additional element effects a transformation or reduction of a particular article to a different state or thing; and
an additional element applies or uses 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.
Step 2B: Consideration of Additional Elements and Significantly More
The claimed method also recites "additional elements" that are not limitations drawn to an abstract idea. The recited additional elements are drawn to:
1. receiving a selection of an initial samples comprising biological samples treated with an analyte and performing optical force-based measurements, wherein the sample is a cell (as recited in claim 8) the analyte comprises a biological constituent or viral constituent (as recited in claim 9 and 11), as in claims 1, 8-9 and 11.
3. the cells are present in a monolayer, suspension or embedded in a matrix, as in claim 15.
4. the cells are sampled from an ongoing process, as in claim 17.
5. calibration objects comprising beads or particles that are spherical or non-spherical shapes, and wherein the calibration objects are mixed into samples and can be differentiated from cell samples based on brightfield image analysis of the cells, as in claims 18-20 and 22.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because laser forced cytology to study characteristics of viral infections of cells is well known, routine and conventional. At least Hebert et al. (2014) evidence that optical chromatograph (i.e. optical force) is well known for studies of cells including viral infection of cells (Abstract); Hebert et al. teach that optical forces have been used to manipulate and interrogate cells and bacterial spores (page 1473, col. 1, par. 1) and viruses (Abstract), as in claims 1, 7-9 and 11. Liu et al. (Anal. Bioanal Chem (2008) vol. 391 pgs. 2443-2452) further evidence that measurement of cellular characteristics with optical fluidic systems is routine conventional and well understood.
Trapping cells in a suspension for analysis is also well known, routine and conventional. Hebert et al. teach trapping cells between microspheres (page 1473, col. 1, par. 2)(i.e. suspension or calibration objects which are particles that can be differentiated from the cells), as in claims 15 and 17-22.
Furthermore, the recited additional elements of claims 7-9, 11, 15, and 17-22 are recited tangentially to the abstract idea of developing a response metric to describe cellular response to the stimuli. The limitations regarding the cell sample, virus, and suspension are not meaningfully integrated with the judicial exception. Viewed as a whole, these additional claim element(s) do not provide meaningful limitation(s) to transform the abstract idea recited in the instantly presented claims into a patent eligible application of the abstract idea such that the claim(s) amounts to significantly more than the abstract idea itself. Therefore, the claim(s) are rejected under 35 U.S.C. 101 as being directed to non-statutory subject matter.
Response to Arguments
Applicant's arguments filed 10/22/2025 have been fully considered but they are not persuasive.
Applicants argue (Remarks, page 8, par. 2) that a known initial sample and unknown sample undergo a cellular transformation, both of which are measured using a particular machine, which is the laser force cytology analyzer. Applicants argue that the claimed method effects the transformation of biological cells.
In response, Applicants are arguing limitations not recited in the claims. The claims do not recite using a particular machine. In claim 1, a cell sample treated with generically recited “stimuli” is received as an initial step. The claims do not recite any transformation of cells, including the unknown sample. Furthermore, the steps reciting measuring with “a laser force cytology analyzer,” does not recite a particular machine. A description or definition of the “laser force cytology analyzer” is not provided in the specification. The analyzer reads on a generic computer of algorithm for measuring parameters, as described in the specification (par. 0040-0041).
Applicants argue (Remarks, page 9) that the amended claim integrates the alleged abstract idea into a practical application through application of optical and fluidic measurements. Applicants argue that the laser force cytology analyzer is used to measure changes in biological cells, sub-cellular components or fractions. Applicants point to the specification (par. 0002) disclosing that the instant invention overcomes challenges by providing novel methods related to biophysical and biochemical cellular monitoring and quantification including intelligent analytical algorithms.
In response, the structure of the “analytical algorithms” is not recited. The claims are drawn to measuring information by a laser force cytology analyzer. The “analyzer” is generically recited and reads on any algorithm including math or a generic computer used to measure optical and fluidic force-based parameters which include any of the parameters recited in claim 1. The claims do not recite any additional elements that integrate the recited abstract idea into a practical application. Categories of practical application are recited above under Step 2A Pong Two. Furthermore, the claims do not recite any additional elements to reflect an improvement to technology. Measuring parameters related to optical fluidic force, determining a response metric with the parameters, measuring another response from an unknow sample using the analyzer and using the response metric to quantify stimuli of the unknow sample, are all analysis steps that read on mental processes or math. Such is not deemed to be an improvement to technology.
Applicants argue (Remarks, page 10, part c.) that the claims recite transforming biological samples into different forms suitable for measurement devices that generate quantifiable data describing cellular response.
In response, the step of receiving samples with biological cells treated with stimuli or analyte is not a practical application of the abstract idea; the abstract idea is not integrated into an additional element that effects a transformation or reduction of a particular article to a different state or thing. See MPEP 2106.05(c). This first step of receiving is part of the initial data collection step, as described in MPEP 2106.05(g). However, even so, how the data is collected from the received samples is not recited.
Applicants argue (Remarks, page 11) that under Step 2B, the claims are drawn to significantly more than the judicial exception. Applicants argue that Hebert cited in the rejection above does not teach determining a metric (RM) to describe cellular response to the one or more stimuli, and a cellular response to the one or more stimuli or analytes of an unknown sample.
In response, applicants are arguing limitations that fall into the category of abstract ideas under Step 2A Prong One. These limitations are not analyzed with regard to whether they are routine, conventional and well understood under Step 2B. Herbert (2014) and Lui (2008) are cited above to evidence that optical force microscopy and optical fluidic systems for interrogating cells are routine conventional and well understood. However, the claims have been amended to recite a “laser force cytology analyzer” which reads on an algorithm or generic computer.
Applicants argue (Remarks, page 12, par. 3) that the claims are analogous to the subject matter found in Thales Visionix Inc.
In response, in Thales, the courts determined that it was not merely the use of sensors that added significantly more to the claimed process but rather it was the non-unconventional placement of the sensors that rendered the claims as whole to be patent eligible. In contrast, the instant claims do not recite any non- “routine, conventional and well understood” additional elements.
Claim Rejections - 35 USC § 112(a) / 112-1st paragraph
The following is a quotation of the first paragraph of 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 1-3, 6, 8, 9, 11, 15, 17-20 and 22 are rejected under 35 U.S.C. 112(a), 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(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 has been amended to recite measuring one or more optical and fluidic force fluid-based parameters of biological cells or sub-cellular components or fractions using at least one analyzer comprising a laser force cytology analyzer, and measuring, using the laser force cytology analyzer, a cellular response to the stimuli. Claim 1 is therefore drawn to a laser force cytology analyzer configured to measure one or more optical and fluidic force fluid-based parameters of biological cells or sub-cellular components or fractions and a cellular response. A review of the specification shows that the recited parameter measuring can be performed by an “intelligent algorithm” or a computer (par. 0040-0041). However a written description of an "analyzer” that measures optical and fluidic force fluid-based parameters and cell stimuli has not been provided. The specification does not have written description support for an “analyzer” comprising a “laser force cytology analyzer” that performs measurements of optical and fluidic force fluid-based parameters and cellular response.
Claim Rejections - 35 USC § 112(b) / 112-2nd paragraph
The rejection of over claim 2 and claim 6 in the previous Office action, for reciting “in a similar manner” is withdrawn in view of arguments and amendments filed 10/22/2025.
The instant rejection is maintained and further modified in view of Applicant’s amendments filed 10/22/2025.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 6, 8, 9, 11, 15, 17-20 and 22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 1 recites “using the RM to quantify the one or more stimuli or analytes to which the at least one unknown sample was treated.” The instant limitation sets forth a use without limitations or steps describing how that use is achieved. The limitation does not recite what process or steps are actually performed by “using” the RM to quantify one or more stimuli or analytes. See MPEP 2173.05(q). The instant claim is vague and indefinite because it is not clear what process is intended so as to use the response metric to quantify stimuli.
Claim 1 has been amended to recite measuring one or more optical and fluidic force fluid-based parameters of biological cells or sub-cellular components or fractions using at least one analyzer comprising a laser force cytology analyzer, and measuring, using the laser force cytology analyzer, a cellular response to the stimuli. As set forth under 35 USC 112(a) above, the specification does not set forth written description for a “laser force cytology analyzer.” The recited “laser force cytology analyzer” is interpreted as a structure that is capable of measuring optical fluidic force-based parameters and a cellular response. However, it is not clear what the structure of the laser force cytology analyzer is; it is not clear if the analyzer is an algorithm with a set of instructions, a laser force cytology apparatus with microfluids and optics, or a generic computer.
Response to Arguments
Applicant's arguments filed 10/22/2025 have been fully considered but they are not persuasive.
Applicants point to (Remarks, page 13-14) the specification teaching that LFC (liquid force cytology) has the ability to measure subtle changes which is the Response Metric. Applicants point to (par. 0049) disclosing Figure 1 and an intelligent algorithm process. Applicants point to (par. 0012) disclosing determining cellular changes by sampling at various dilutions. Applicants point to (par. 0041) disclosing determining Radiance specific parameters.
In response, claim 1 recites a step of “using the RM to quantify the one or more stimuli or analytes to which the at least one unknown sample was treated.” However, the RM is a response metric determined from any of the optical and fluidic force-based parameters recited in claim 1. It is unclear what steps are performed when “using” the RM determined from any of the parameters (such as size, linear velocity, minor axis, images including grey scale features, eccentricity deformability, number of debris-sized particles, volume, number of trapped cells, etc.) to quantify one or more stimuli or analytes to which an unknown sample was treated. For example, supposing that the measured optical and fluidic force-based parameter comprises “number of debris-sized particles” or “minor axis.” It is unclear how this parameter would be used as part of a RM to quantify stimuli in another [unknown] sample. Neither the claims nor the specification provide sufficient clarification and therefore the step of “using” the RM to quantify” is unclear with respect to what steps are being performed.
Claim Rejections - 35 USC § 102
The rejection of claims 1-3, 5-9, 11, 15, 17-20 and 22 under 35 U.S.C. 102(b) as being anticipated by Hebert et al. is withdrawn in view of Applicant’s amendments filed 12/02/2024.
Claim Rejections - 35 USC § 103
The rejection of claims 1-3, 5-9, 11, 15, 17-20 and 22 under 35 U.S.C. 103(a) as being unpatentable over Hebert et al. (Analyst, vol. 139 (2014) pg. 1472; IDS 11/21/2023) is withdrawn in view of Applicant’s arguments.
Noted Relevant Art
Wang, Mark M., et al. "Microfluidic sorting of mammalian cells by optical force switching." Nature biotechnology 23.1 (2005): 83-87.
E-mail communication Authorization
Per updated USPTO Internet usage policies, Applicant and/or applicant’s representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EFS Web (using PTO/SB/439) or Central Fax (571-273-8300):
Recognizing that Internet communications are not secure, I hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. I understand that a copy of these communications will be made of record in the application file.
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
Conclusion
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anna Skibinsky whose telephone number is (571) 272-4373. The examiner can normally be reached on 12 pm - 8:30 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Ram Shukla can be reached on (571) 272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Anna Skibinsky/
Primary Examiner, AU 1635