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 .
Claim Status
Claims 1-20 are currently pending.
Priority
The instant Application is a Continuation of US 15/885,463, filed 31 January 2018, now US Patent 11,458,509. The Effective Filing Date assigned for each of claims 1-20 is therefore 31 January 2018.
Information Disclosure Statement
The Information Disclosure Statements filed 21 October 2022; 1 June 2023; and 16 April 2024 are in compliance with the provisions of 37 CFR 1.97 and have therefore been considered. Signed copies of the IDS documents are included with this Office Action.
Drawings
The Drawings submitted 21 October 2022 are accepted.
Specification
All references in this Office Action to “the Specification” refer to the PG Publication US20230082983.
Claim Interpretation
Claim terms as follows are interpreted as defined in the Specification:
Sub-units are defined as representing biological processes external to metabolism, wherein each sub-unit contains its own system of production and consumption of molecules [0021]. Upstream sub-units provide raw inputs to Flux Balance Analysis (FBA) metabolism, as described at [0022] and Down-stream sub-units include downstream cellular processes which take as raw input the products of an FBA metabolic system [0023]. The sub-units may be interchangeable [0025]. In all, the sub-units are mathematical models of cellular processes [0026].
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 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
The instant rejection reflects the framework as outlined in the MPEP at 2106.04:
Framework with which to Evaluate Subject Matter Eligibility:
(1) Are the claims directed to a process, machine, manufacture or composition of matter;
(2A) Prong One: Do the claims recite a judicially recognized exception, i.e. a law of nature, a natural phenomenon, or an abstract idea;
Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application (Prong Two); and
(2B) If the claims do not integrate the judicial exception, do the claims provide an inventive concept.
Framework Analysis as Pertains to the Instant Claims:
Step 1 Analysis: Are claims directed to process, machine, manufacture/composition of matter
With respect to step (1): yes, the claims are directed to a method (1-10) and non-transitory computer readable storage medium containing computer program code (11-20).
Step 2A, Prong 1 Analysis: Do claims recite abstract idea
With respect to step (2A)(1), the claims recite abstract ideas. The MPEP at 2106.04(a)(2) further explains that abstract ideas are defined as:
mathematical concepts, (mathematical formulas or equations, mathematical relationships and mathematical calculations);
certain methods of organizing human activity (fundamental economic practices or principles, managing personal behavior or relationships or interactions between people); and/or
mental processes (procedures for observing, evaluating, analyzing/ judging and organizing information).
With respect to the instant claims, under the (2A)(1) evaluation, the claims are found herein to recite abstract ideas that fall into the grouping of mental processes (in particular procedures for observing, analyzing and organizing information) and in conjunction with mathematical concepts (in particular mathematical relationships and formulas).
Note: The claims elements are italicized herein to highlight the judicial exceptions in the claim steps and underlined to represent the additional claim elements.
Claims 1 and 11:
receiving an initial state dataset, the initial state dataset including information representing an initial concentration of at least one molecule within an existing cellular environment of at least one biological cell and information representing an initial net demand for at least one molecule in a plurality of sub-units, wherein the plurality of sub-units represent a plurality of biological processes external to a metabolism of the at least one biological cell;
calculating a first flux dataset based on a model and an objective function, wherein the model is configured to model the metabolism of the at least one biological cell, and wherein the objective function is configured based on a stoichiometric matrix and target values derived from the initial net demand-wherein steps directed to “calculating” are those directed to mathematical operation wherein objective functions and model parameters are variables for said calculation. The instant Specification provides that a flux dataset calculation includes [0030], “a system of equations describing the stoichiometric reaction constraints for each molecule in the FBA metabolism 110 is defined. The flux values of each molecule (e.g., the input supply of FBA metabolism 110 and the output production of FBA metabolism 110) are unknowns, and are solved for by summing the modified weighted flux values to produce an objective function. The objective function is then maximized given the constraints of the system of equations. Solving the maximization problem produces a set of flux value solutions which make up the input flux dataset 108 and the output flux dataset 112. The flux value solutions of the input flux dataset 108 and output flux dataset 112 represent the steady state behavior of FBA metabolism 110 given the existing supply and demand within upstream sub-units 102 and downstream sub-units 114”. As such, the Specification details that said operations are indeed mathematical.
generating a subsequent state dataset based on the initial state dataset and the first flux dataset, the subsequent state dataset including information representing a simulated concentration of the at least one molecule within the existing cellular environment of the at least one biological cell and information representing a subsequent net demand for the at least one molecule in the plurality of sub-units-wherein said operation is an “update” to the calculations of the initial state as in the Specification at least at [0038]. As such, said operation is a mathematical process.
calculating a second flux dataset based on the model and an updated objective function, wherein the updated objective function is configured based on the objective function and target values derived from the subsequent net demand-wherein said operation is a calculation as above of a second flux based on the updated information and is therefore a mathematical process
calculating a difference between the first flux dataset and the second flux dataset, the calculated difference representing an outcome of a cell process of the at least one biological cell wherein “difference” operations are calculations that require mathematical operation of subtracting one value from another.
Claims 2 and 12:
wherein the initial net demand for the at least one molecule in the plurality of sub-units is determined based on: an initial rate of supply in a first sub-unit of the plurality of sub-units, the first sub-unit representing at least one biological process upstream from the metabolism of the at least one biological cell; and an initial rate of demand in a second sub-unit of the plurality of sub-units, the second sub- unit representing at least one biological process downstream from the metabolism of the at least one biological cell-wherein said operation is a mathematical operation as disclosed in the Specification at least at [0026] wherein “each sub-unit implicitly (as in PDE, ODE and Monte Carlo models) or explicitly (as in FBA or rate kinetic models) contains a set of rates at which the sub-unit intakes raw inputs and outputs products. In some examples, an implicit rate of demand may be determined by a difference between an existing concentration of a molecule and a projected concentration in a future time step. For the purposes of the modified FBA system 100, the behavior of the upstream sub-units 102 and downstream sub-units 114 that is relevant to FBA metabolism 110 is the conversion rate of reactants to products within each of the sub-units, since this is the primary value translatable into the terms governing FBA (e.g., the flux values). For each sub-unit, the intake rate of inputs represents the demand for each of the input molecules, while the output rate of products represents the supply of each of the output molecules”.
Claims 3 and 13:
wherein the initial state dataset further includes information representing an initial concentration of at least one molecule within the plurality of sub-units
Claims 4 and 14:
wherein the initial state dataset further includes a set of intrinsic rate parameters, the set of intrinsic rate parameters representing at least one constraint of the metabolism of the at least one biological cell
Claims 5 and 15:
wherein the set of intrinsic rate parameters includes at least one of: a proportional rate limit, an integral rate limit, and a derivative rate limit, wherein said operations directed to proportion, integral rate limits and derivative limits are mathematical operations by definition.
Claims 6 and 16:
wherein calculating the first flux dataset based on the model and the objective function comprises subtracting the target values derived from the initial net demand from proportional flux contributions calculated based on a set of flux values, wherein “subtraction” is a mathematical operation by definition.
Claims 7 and 17:
wherein calculating the second flux dataset based on the model and the updated objective function comprises subtracting the target values derived from the subsequent net demand from proportional flux contributions calculated based on a set of flux values, wherein “subtraction” is a mathematical operation by definition.
Claims 8 and 18:
wherein at least one biological process of the plurality of biological processes corresponds to at least one of transcription, translation, cellular communication, cellular reproduction, and cellular transport
Claims 9 and 19:
wherein: first flux dataset and the second flux dataset, the first flux dataset is associated with a first time; the second flux dataset is associated with a second time after the first time; and the difference between the first flux dataset and the second flux dataset represents metabolic production over a time interval between the first time and the second time
Claims 10 and 20:
wherein the outcome of the cell process of the at least one biological cell comprises at least one of a concentration of a molecule within a production network of the at least one biological cell
Further limitations in claims 11-20 include:
non-transitory computer readable storage medium containing computer program code executable on a processor for causing the processor to perform operations
Hence, the claims explicitly recite numerous elements that, individually and in combination, constitute abstract ideas.
The abstract ideas recited in the claims are evaluated under the Broadest Reasonable Interpretation (BRI) and determined herein to each cover performance either in the mind (calculations by hand or pen and paper or computer as a tool) and performance by mathematical operation. There are no specifics as to the methodology involved in said operations beyond mental process and mathematical operation. Therefore, under the BRI of the instant set of claims, said data are then used in a series of calculations for solution fluxes and provision of determinations that include assessment of a difference in the data as calculated. The claims represent noting more than abstract mathematical manipulation and can be performed mentally using pen and paper. Other steps, recited in dependent claims, further include that said modeling techniques are performed using mathematical techniques. These recitations are similar to the concepts of collecting information, analyzing it and providing certain results from the collection and analysis (Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), organizing and manipulating information through mathematical correlations (Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)) and comparing information regarding a sample or test to a control or target data in (Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)) that the courts have identified as concepts that can be practically performed in the human mind with pen and paper, and can include mathematical concepts.
Further, see MPEP § 2106.04(a)(2), subsection III. The courts do not distinguish between mental processes that are performed entirely in the human mind and mental processes that require a human to use a physical aid (e.g., pen and paper or a slide rule) to perform the claim limitation (see, e.g., Benson, 409 U.S. at 67, 65, 175 USPQ at 674-75, 674: noting that the claimed "conversion of [binary-coded decimal] numerals to pure binary numerals can be done mentally," i.e., "as a person would do it by head and hand."); Synopsys, Inc. v. Mentor Graphics Corp., 839 F.3d 1138, 1139, 120 USPQ2d 1473, 1474 (Fed. Cir. 2016): holding that claims to a mental process of "translating a functional description of a logic circuit into a hardware component description of the logic circuit" are directed to an abstract idea, because the claims "read on an individual performing the claimed steps mentally or with pencil and paper"). Nor do the courts distinguish between claims that recite mental processes performed by humans and claims that recite mental processes performed on a computer. As the Federal Circuit has explained, "[c]ourts have examined claims that required the use of a computer and still found that the underlying, patent-ineligible invention could be performed via pen and paper or in a person’s mind" (see Versata Dev. Group v. SAP Am., Inc., 793 F.3d 1306, 1335, 115 USPQ2d 1681, 1702 (Fed. Cir. 2015); Mortgage Grader, Inc. v. First Choice Loan Servs. Inc., 811 F.3d 1314, 1324, 117 USPQ2d 1693, 1699 (Fed. Cir. 2016): holding that computer-implemented method for "anonymous loan shopping" was an abstract idea because it could be "performed by humans without a computer").
Step 2A, Prong 2 Analysis: Integration to a Practical Application
Because the claims do recite judicial exceptions, direction under (2A)(2) provides that the claims must be examined further to determine whether they integrate the abstract ideas into a practical application (MPEP 2106.04(d). A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. This is performed by analyzing the additional elements of the claim to determine if the abstract idea is integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the abstract idea, the claim is said to fail to integrate the abstract idea into a practical application (MPEP 2106.04(d).III).
With respect to the instant recitations, the claims recite the additional elements as underlined above.
Additional elements in the instant claims directed to data gathering perform functions of collecting the data needed to carry out the abstract idea. Data gathering does not impose any meaningful limitation on the abstract idea, or on how the abstract idea is performed. Data gathering steps are not sufficient to integrate an abstract idea into a practical application. (MPEP 2106.05(g). Those include the data specific to the claims such as receiving “datasets” and further definition of the information of those datasets.
Further said steps also include those that recite a computer readable medium, wherein said media is executable on a processor and serves as the vehicle for data gathering in the claim and are part of a general purpose computer system and there are no details herein wherein of how the specific computer structures are used to implement the judicial exceptions beyond generic computing operations, i.e., the computer elements of the claims do not provide improvements to the functioning of the computer itself (see: DDR Holdings, LLC v. Hotels.com LP); they do not provide improvements to any other technology or technical field (see: Diamond v. Diehr); nor do they utilize a particular machine (see: Eibel Process Co. v. Minn. & Ont. Paper Co.). Hence, these are mere instructions to apply the judicial exception using a computer, and therefore the claim does not provide integration into a practical application of any judicial exception.
Step 2B Analysis: Do Claims Provide an Inventive Concept
The claims are lastly evaluated using the (2B) analysis, wherein it is determined that because the claims recite abstract ideas, and do not integrate that abstract ideas into a practical application, the claims also lack a specific inventive concept. Applicant is reminded that the judicial exception alone cannot provide the inventive concept or the practical application and that the identification of whether the additional elements amount to such an inventive concept requires considering the additional elements individually and in combination to determine if they provide significantly more than the judicial exception. (MPEP 2106.05.A i-vi).
With respect to the instant claims, the additional elements of data gathering described above do not rise to the level of significantly more than the judicial exception. As directed in the Berkheimer memorandum of 19 April 2018 and set forth in the MPEP, determinations of whether or not additional elements (or a combination of additional elements) may provide significantly more and/or an inventive concept rests in whether or not the additional elements (or combination of elements) represents well-understood, routine, conventional activity. Said assessment is made by a factual determination stemming from a conclusion that an element (or combination of elements) is widely prevalent or in common use in the relevant industry, which is determined by either a citation to an express statement in the specification or to a statement made by an applicant during prosecution 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 to Palsson et al. (2017/0140092-IDS reference) discloses that it was well-known and routine in the art to get data pertaining to molecular demand for operation in a flux balance analysis (FBA) environment. Said portions of the prior art are, for example, [0004], discussing the cellular behavior data and [0005] discussing constraint-based modeling using biological systems data. As such, activities such as data gathering do not improve the functioning of a computer, or comprise an improvement to any other technical field; they do not require or set forth a particular machine; they do not effect a transformation of matter; nor do they provide a non-conventional or unconventional step. Rather, the data gathering steps as recited in the instant claims constitute a general link to a technological environment which is insufficient to constitute an inventive concept which would render the claims significantly more than the judicial exception (MPEP2106.05(g)&(h)).
With respect to the claims to the computer readable storge medium executable on a processor, the computer-related elements or the general purpose computer do not rise to the level of significantly more than the judicial exception. Further exemplified prior art to, for example, Palsson et al. (2017/0140092-IDS reference) teaches that computing elements are routine, well-understood and conventional in the art [0019]. Further the art to Oberhardt et al. (Methods in Molecular Biology, Systems Biology (2009) Vol. 500:61-80-IDS reference) discloses that FBA may be run on any conventional computing system and does not require specialized computing hardware, being executable on a standard desktop using a variety of software tools [page 66]. The additional elements are set forth at such a high level of generality that they can be met by a general purpose computer. Therefore, the computer components constitute no more than a general link to a technological environment, which is insufficient to constitute an inventive concept that would render the claims significantly more than an abstract idea (see MPEP 2106.05(b)I-III).
The dependent claims have been analyzed with respect to step 2B and none of these claims provide a specific inventive concept, as they all fail to rise to the level of significantly more than the identified judicial exception.
For these reasons, the claims, when the limitations are considered individually and as a whole, are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
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.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over (2017/0140092-IDS reference) to Palsson et al. in view of Karr et al. (Cell (2012) Vol. 150:389-401-IDS reference).
The instant claims are directed to a method (claim 1) an non-transitory computer readable storage medium…causing a processor to perform (claim 11):
receiving an initial state dataset, the initial state dataset including information representing an initial concentration of at least one molecule within an existing cellular environment of at least one biological cell and information representing an initial net demand for at least one molecule in a plurality of sub-units, wherein the plurality of sub-units represent a plurality of biological processes external to a metabolism of the at least one biological cell (Palsson et al. discloses initial state data based on net demand of molecules contributing to a FBA system wherein the dataset includes production and consumption of molecules outside of the FBA system [0026]; [0038];[0054]; [0055]);
calculating a first flux dataset based on a model and an objective function, wherein the model is configured to model the metabolism of the at least one biological cell, and wherein the objective function is configured based on a stoichiometric matrix and target values derived from the initial net demand (Palsson et al. discloses the calculating of stoichiometric matrices and objective functions as limited by initial datasets [0041]; [0056]; [0059]; [0075]);
generating a subsequent state dataset based on the initial state dataset and the first flux dataset, the subsequent state dataset including information representing a simulated concentration of the at least one molecule within the existing cellular environment of the at least one biological cell and information representing a subsequent net demand for the at least one molecule in the plurality of sub-units (Palsson et al. discloses subsequent datasets based on integration of previous datasets [0063]);
calculating a second flux dataset based on the model and an updated objective function, wherein the updated objective function is configured based on the objective function and target values derived from the subsequent net demand (Palsson et al. impose updated constraints based on the effect on the reaction network performance [0066];[0070]; [0075]); and
calculating a difference between the first flux dataset and the second flux dataset, the calculated difference representing an outcome of a cell process of the at least one biological cell (Palsson et al. discloses rate of change from an initial state to the final state of an organism [0045]; [0075]).
With respect to the non-transitory computer-readable storage medium containing computer program code executable on a processor for executing the methods as claimed in instant claims 1-11, the prior art to Palsson et al. discloses operation on a computer-readable medium [0019]; [0027]; [0043]. The prior art as pertains to claims 1-11 above is applied equally to claims 12-22 for the reasons as set forth in the above rejections and outlined below to include the corresponding method and computer-readable medium claims. Further, the prior art as disclosed is relied upon herein for the totality of the teachings disclosed in each of said references.
With respect to claims 2 and 12 Palsson et al. disclose reactants substrates and products and the stoichiometric coefficients that relate the substrate and the product in a system and the constraints for a plurality of reactions [0019]-[0020].
With respect to claims 3 and 13, Palsson et al. disclose the concentration of molecules and excess concentrations in a system. This is accounted for by the definition of the solution space and the determination of solutions as conditions vary in the system, For example, maximum ATP productions conditions as described at [0025].
With respect to claims 4 and 14, Palsson et al. disclose intrinsic rate parameters associated with a reaction [0045]; [0046].
With respect to claims 5 and 15, Palsson et al. disclose proportional rate parameters, as Palsson et al. disclose the differences between initial and a changed state rate [0045].
With respect to claims 6 and 7, and 16 and 17, Palsson et al. disclose datasets associated with a first and subsequent time and wherein differences between initial and subsequent states are calculated [0045]; [0057]; [0071].
With respect to claims 8 and 18, Palsson et al. disclose biological processes that include transport [0030]; transcription and translation and interaction [0033].
With respect to claim 9 and 19, Palsson et al. disclose flux over time including a first and second determination [0021]; [0075].
With respect to claims 10 and 20, Palsson et al. disclose determination of reaction regulation proceeding to a desired threshold concentration that is representative of system regulation [0062]; [0081].
With respect to claims 1 and 11, Palsson et al. do not specifically disclose the “sub-units” as claimed herein wherein the sub-units are external to an FBA system and wherein sub-units are defined as above (see claim interpretation). With respect to claims 2 and 12, Palsson et al. does not specifically disclose said sub-units up and down-stream as claimed.
However, the prior art to Karr et al. discloses a whole-cell computational model for the life cycle of the human pathogen Mycoplasma genitalium (M. genitalium) that accounts for all of the molecule components and their interactions (abstract; page 389). The whole-cell model as proposed by Karr et al. divides the functionality of the cell into modules (interpreted as “sub-units” for purposes of the instant claims) wherein each modules is evaluated independently of the others and integrated as sub-models together (pages 389-390; Figure 1, A, B).
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 have integrated the methods and systems of Palsson et al. into the whole-cell modeling techniques disclosed in Karr et al., as both prior art references include the elements of flux balance analysis methodology to assess regulatory cellular networks and one of skill in the art could have readily combined the elements as claimed by the known methods for FBA and said combination would have resulted in the same function as provided for in said references individually. One would have had a reasonable expectation of success in so doing because Palsson et al. discuss the power of computational approaches for reconstruction of biological networks by modeling the entire solution space [0005] and the use of constraint-based approaches to do so in the context of genome-scale models [0085], including upstream and downstream reactions [0033].
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.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11,508,459. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are directed to a method an non-transitory computer readable storage medium with instructions for: receiving an initial state dataset, the initial state dataset including information representing an initial concentration of at least one molecule within an existing cellular environment of at least one biological cell and information representing an initial net demand for at least one molecule in a plurality of sub-units, wherein the plurality of sub-units represent a plurality of biological processes external to a metabolism of the at least one biological cell; calculating a first flux dataset based on a model and an objective function, wherein the model is configured to model the metabolism of the at least one biological cell, and wherein the objective function is configured based on a stoichiometric matrix and target values derived from the initial net demand; generating a subsequent state dataset based on the initial state dataset and the first flux dataset, the subsequent state dataset including information representing a simulated concentration of the at least one molecule within the existing cellular environment of the at least one biological cell and information representing a subsequent net demand for the at least one molecule in the plurality of sub-units; calculating a second flux dataset based on the model and an updated objective function, wherein the updated objective function is configured based on the objective function and target values derived from the subsequent net demand; and calculating a difference between the first flux dataset and the second flux dataset, the calculated difference representing an outcome of a cell process of the at least one biological cell.
Claims of the ‘459 patent are directed to: A method for simulating an outcome of a cell process of at least one cell in a production network, the method comprising: receiving an initial state dataset based on initial net demand for a plurality of molecules in a plurality of sub-units representing production and consumption of molecules external to a flux balance analysis (FBA) system, wherein multiple sub-units of the plurality of sub-units represent transcription, translation, cellular communication, cellular respiration, cellular reproduction, or cellular transport (claim 8 and 18 of instant claims include: transcription, translation, cellular communication, and cellular transport); calculating an initial solution flux dataset by evaluating the FBA system based on a stoichiometric matrix and an objective function, the objective function based on a difference between a first target value for each molecule of the plurality of molecules and a first proportional flux contribution of each molecule of the plurality of molecules, wherein the first target value is included in a set of initial target values calculated based on the initial state dataset; receiving a subsequent net demand for the plurality of molecules from initial solutions to the plurality of sub-units; calculating a subsequent state dataset for the plurality of molecules in the plurality of sub-units based on the initial state dataset, the initial solution flux dataset, and the subsequent net demand; updating the objective function, the updated objective function based on a difference between a second target value for each molecule of the plurality of molecules and a second proportional flux contribution of each molecule of the plurality of molecules, wherein the second target value is included in a set of subsequent target values calculated based on the subsequent state dataset; calculating a subsequent solution flux dataset by evaluating the FBA system with the updated objective function; and determining the outcome of the cell process of the at least one cell, the determining includes calculating a difference between the subsequent solution flux dataset and the initial solution flux dataset, wherein the outcome of the cell process corresponds to an estimation of a growth rate of the at least one cell, and wherein an accuracy of the updated objective function is determined based on a comparison of the estimation of the growth rate of the at least one cell to an actual growth rate of the at least one cell.
The claims of the ‘459 patent further includes that the outcome of the cell process corresponds to an estimation of growth rate wherein the instant claims include outcome of a cell process of at least one biological cell. Cellular processes are defined in the instant Specification as those that include cellular growth and therefore said a cellular process is fairly and obviously interpreted herein as including a “growth rate”. recitations are obvious . See the instant Specification at least at [0017]; [0041]; [0052].
E-mail Communications 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 following form via EFS-Web or Central Fax (571-273-8300): PTO/SB/439. Applicant is encouraged to do so as early in prosecution as possible, so as to facilitate communication during examination.
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web 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.
Inquiries
Papers related to this application may be submitted to Technical Center 1600 by facsimile transmission. Papers should be faxed to Technical Center 1600 via the PTO Fax Center. The faxing of such papers must conform to the notices published in the Official Gazette, 1096 OG 30 (November 15, 1988), 1156 OG 61 (November 16, 1993), and 1157 OG 94 (December 28, 1993) (See 37 CFR § 1.6(d)). The Central Fax Center Number is (571) 273-8300.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lori A. Clow, whose telephone number is (571) 272-0715. The examiner can normally be reached on Monday-Thursday from 11:00AM to 9:00PM ET.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Karlheinz Skowronek can be reached on (571) 272-9047.
Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to (571) 272-0547.
Patent applicants with problems or questions regarding electronic images that can be viewed in the Patent Application Information Retrieval system (PAIR) can now contact the USPTO’s Patent Electronic Business Center (Patent EBC) for assistance. Representatives are available to answer your questions daily from 6 am to midnight (EST). The toll free number is (866) 217-9197. When calling please have your application serial or patent number, the type of document you are having an image problem with, the number of pages and the specific nature of the problem. The Patent Electronic Business Center will notify applicants of the resolution of the problem within 5-7 business days. Applicants can also check PAIR to confirm that the problem has been corrected. The USPTO’s Patent Electronic Business Center is a complete service center supporting all patent business on the Internet. The USPTO’s PAIR system provides Internet-based access to patent application status and history information. It also enables applicants to view the scanned images of their own application file folder(s) as well as general patent information available to the public.
/Lori A. Clow/ Primary Examiner, Art Unit 1687
Prosecution Insights