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 .
Response to Amendment
This office action is responsive to the amendment filed 31 July 2026. As directed by the amendment claims 1-4, 6, 8-11, 14-18, 26-28, and 30-32 are pending in this application. The amendment to claim 1 has overcome the previous 35 USC 112 rejection. The applicant’s amendments to the title are accepted.
Response to Arguments
Applicant's arguments filed 31 July 2026 have been fully considered but they are not persuasive.
Applicant argues, “A. The Office has failed to make a Prima Facie case. MPEP 2143.03
Applicant respectfully submits that the Office has mischaracterized the cited art. The Examiner rejects Claim 1 as obvious over Dumont (US 2018/0296759) in view of Kuchimanchi (US 2020/0312436). The Examiner maps the pump, the computer-deliverable program, and the delivery step onto Dumont, and expressly acknowledges that Dumont does not teach delivering "at a desired flow rate or flow constant as determined by said patient's own rate constants identified in (i)." To supply that admittedly missing limitation, the Examiner turns to Kuchimanchi (citing Kuchimanchi [0061], [0083]-[0086], [0143]).
The rejection is respectfully traversed. The limitation the combination must supply is not supplied by either reference, alone or in combination; the paragraphs the Examiner cites do not
disclose what the rejection attributes to them; and the articulated reason to combine rests on that same absent disclosure. In short, the Office has failed to establish a prima facie case. MPEP 2143.
" Kuchimanchi [0061], cited for calculating "the rate constants of a patient" and for
updating constants "for intravenous fluid delivery ... in order to reach optimal rates," is directed to server topology and to periodically updating pharmacokinetic models with dosing and patient information. It contains none of "intravenous fluid delivery," "optimal rates," or "flow rate constants," Kuchimanchi is silent as to calculating a patient's rate constants.
" Kuchimanchi [0143], also cited for "calculates the rate constants of a patient," is a
general description of computing hardware (FIG. 31) - processor, memory, address/data bus, and interface circuits. Kuchimanchi discloses no rate-constant calculation of any kind.
" Kuchimanchi [0083]-[0086], cited for tailoring "flow rate constants" and preventing
"excess fluid delivery," describe user-interface screens for entering patient information and toggling prior samples on and off. Kuchimanchi discloses neither flow rate constants nor fluid delivery.
" Kuchimanchi [0074], cited for the proposition that "the model accounts for and allows
for steady state functions," addresses volume of distribution at steady state ( i.e. , adding V1 and V2. Kuchimanchi does not disclose steady-state infusion or a steady-state delivery function.
Applicant further notes that the rejection repeatedly characterizes Kuchimanchi as directed to "intravenous fluid delivery," "flow rate constants," and preventing "excess fluid delivery." Kuchimanchi is directed to dosing a therapeutic plasma protein (FVIII), not to intravenous fluid- volume management. The terminology in the rejection does not correspond to Kuchimanchi's actual disclosure, and the record does not establish that Kuchimanchi teaches the limitation for which it is cited. It is incumbent on the Office to point out with particularity where it finds that limitation.
The central distinction. Measuring how much drug is present in the blood over time is not the same thing as determining a patient's own rate constants for transport to the site of action. One can record a blood-concentration curve for an individual without ever computing that individual's transport rate constants. The claimed method computes those rate constants and uses them; the cited references do not. The Office has already recognized this as to Dumont, stating that Dumont "does not specifically teach delivering ... as determined by said patient's own rate constants identified in (i)."
Kuchimanchi does not supply what Dumont lacks. Kuchimanchi is directed to dosing clotting factor VIII, a therapeutic protein that acts within the blood itself. Its model has two blood-based compartments describing how the protein distributes within, and is cleared from, the blood. It contains no compartment for a site of action outside the blood, and no rate constant for transport of a drug to such a site. The one patient-specific number Kuchimanchi derives from a patient's own blood samples is a measure of how quickly the protein leaves the blood, used only to decide how much weight to give that patient's samples relative to a population average. It is not a transport-to-active-site rate constant, and it is not used to set the delivered concentration.”
The flow rate as described in Kuchimanchi is considering flow rate of the patient as the drug is delivered by measuring the blood concentration of the drug over time. This measurement is directed at active site administration as the drug delivery rate and concentration are measured together and are the data that is then used to derive rate constants. Although the rate constants are placed into a larger population formula, the rate constant is still being calculated on an individual level as stated in the rejection of claim 1 below.
Applicant argues on page 9, “10. Kuchimanchi - what it actually discloses. Kuchimanchi is directed to dosing clotting factor VIII (FVIII), a therapeutic plasma protein that acts within the blood. Its pharmacokinetic model is a two-compartment model whose parameters are clearance (CL), volumes of distribution (Vi and V2), and inter-compartmental clearance (Q). Those parameters describe elimination and distribution among blood-based compartments. Kuchimanchi discloses no active-site compartment separate from the blood and no rate constant for transport of a drug from an infusion site to a separate active site. There is accordingly no transport-to-active-site rate constant in Kuchimanchi to individualize.
11. Kuchimanchi's one patient-specific value is an exponent, not a rate constant. Kuchimanchi determines its dose from a Bayesian population model built on a cohort of sampled patients, adopting that approach because, in its own words, patient-specific determination is "complex or difficult ... without extensive blood draws." Where it uses a patient's own data, it uses that data to weight the population model. The single patient-specific value it derives is an estimated first-order elimination-rate constant used only to decide how heavily to rely on that patient's samples. It is not a transport-to-active-site rate constant, it does not set the delivered concentration, and it does not solve the inverse problem required to recover the compartmental rate constants.”
The calculation that is performed is a rate constant based on blood distribution over time as the V1 and V2 factors are a measure of time for drug concentration in an active site in which the blood is circulating the drug. The patient specific rate constant is still present as applicant points out for patient sampling but additionally the patient data collection and use is a form of rate constant calculation that updates a model. The language of claim 1 is broad in the fact that it uses the patient’s rate constant as a part of a model and does not necessarily require the rate constant to be that specific. The larger population equation is still a form of rate constant used with individualized data.
Applicant argues on page 9, “12. Topology mismatch. There is also a mismatch of model topology. Kuchimanchi's two compartments are both blood-based - a central and a peripheral plasma compartment (V1 and V2). The distinction that matters is not the number of compartments but their identity: Kuchimanchi has no compartment corresponding to an active site distinct from the blood, and no pathway for transport of a drug from an infusion site to such an active site. That is the transport the claims require. (I note that the claims expressly encompass two-compartment as well as multi-compartment kinetics; my point concerns which compartments are modeled, not how many.)”
The distinction of the model topology is not present in the claims as only describe the steady state as being two compartment or multicompartment. Furthermore, the active site delivery would be calculated as the blood concentration is measured over time. The initial infusion would correspond to the infusion site and the drug concentration over time would correspond to active site concentration.
Applicant argues on pages 9-10, “13. Dumont - population parameters, and a controller that consumes rather than produces rate constants. Dumont's model-predictive controller operates on population pharmacokinetic parameters taken from published models (Schnider- type propofol models). Its effect-site transport constant is a fixed population value (keo = 0.456 min-' for the 18-60 age band), and Dumont's claim 97 recites that the combination of models "comprises an average of the models over the population." Dumont individualizes to the patient by correcting the infusion rate against a measured effect signal (bispectral index or related index of depth of hypnosis) - that is, by feedback on a measured effect, not by deriving that patient's own rate constants from observation. A model-predictive controller of this type takes rate constants as inputs; it does not output them.”
The rate constant output is being combined from the device of Kuchimanchi and utilizes similar equation types. Additionally, the input of a rate constant is present in claim 1 as the rate constant is being used for model updating. The combination of these two pieces of prior art is teaching both the input and output that is required by claim 1.
Applicant argues on pages 10-11, “B. The Limitation at Issue: Delivery Governed by the Patient's Own Transport-to-Active-Site Rate Constants
The claim ties the delivery rate to a specific category of parameter. Step (i) calculates "the rate constants of a patient for transport of a drug from an infusion site to an active site." Step (iv) then delivers the drug "at a desired flow rate or flow constant (k) as determined by said patient's own rate constants identified in (i)." The claimed delivery rate is thus set by this patient's own transport-to-active-site rate constants. That is the limitation the Examiner concedes Dumont lacks, and it is the limitation the combination must supply.
C. Neither Dumont nor Kuchimanchi Supplies Individualized Transport-to-Active-Site Rate Constants Governing Delivery
Taking the references as the Examiner combines them: Dumont does have transport-to-active-site rate constants; its four-compartment PKPD model includes an effect-site compartment with plasma-to-effect-site transport constants. But Dumont populates those constants from a nominal population model (a set of 44 patient models; Dumont [0046], [0085]), and its effect-site transport constant is expressly a fixed population value - Dumont adopts the Schnider population value k _e0 = 0.456 min-' for the 18-60 age band (Dumont [0095]). Dumont individualizes delivery to the patient through closed-loop feedback on a measured depth-of-hypnosis signal, not by deriving this patient's own transport constants. The Examiner's own admission confirms this: Dumont "does not specifically teach delivering at a desired flow rate or flow constant as determined by said patient's own rate constants identified in (i)."
Kuchimanchi does not cure that gap, for two independent reasons:
First, Kuchimanchi discloses no active-site compartment and no rate constant for transport of a drug from an infusion site to an active site. Kuchimanchi is directed to dosing clotting factor VIII (FVIII), a therapeutic plasma protein that acts within the blood. Its pharmacokinetic model is a two-compartment model whose parameters are clearance (CL), volumes of distribution (V1, V2), and inter-compartmental clearance (Q) (Kuchimanchi [0071]-[0074]). These describe elimination and distribution among blood-based compartments; none is a constant for transport of a drug from an infusion site to a separate active site. A reference that discloses no transport-to-active-site rate constant cannot supply the individualized transport-to- active-site rate constant the claim requires.
Second, and independently, to the extent Kuchimanchi uses a patient's own data at all, it uses that data to weight a Bayesian population model, and the only patient-specific constant it derives is an elimination-phase constant - not a transport constant and not a delivery-governing constant. Kuchimanchi builds the profile on "a (Bayesian) model that uses pharmacokinetic profiles of a set of sample representative patients" (Kuchimanchi [0051]), derived from a 152-subject population cohort (Kuchimanchi [0067], [0150]), adopting that approach precisely because "precise patient-specific pharmacokinetic profiles are relatively complex or difficult to determine without extensive blood draws" (Kuchimanchi [0063]). Where Kuchimanchi does derive a single patient-specific constant, it is an elimination-rate estimate used as a weighting ratio against the population elimination constant to decide how heavily to weight the patient's samples; it does not determine the delivery rate, and it is not a transport-to-active-site constant. The combination therefore still lacks the claimed subject matter. Dumont has transport-to-active- site constants but uses population values; Kuchimanchi individualizes, but only elimination/clearance parameters, and has no transport-to-active-site constant to individualize. Even fully merged, the proposed combination yields, at most, an individualized elimination weighting layered on a population transport constant - it never yields the claimed delivery "at a desired flow rate or flow constant as determined by said patient's own [transport-to-active-site] rate constants identified in (i)." This is a gap in the combination itself, not an attack on either reference in isolation. See In re Keller, 642 F.2d 413 (CCPA 1981).”
As mentioned above, the teaching of Kuchimanchi does teach V1 and V2 as concentration over time based on blood volume which means the initial concentration would be the initial site and the active site would be the second concentration used in the calculation. This also factors into the calculation of a value that determines concentration over time which is a rate constant and also a rate constant that is used in a population model. All of these factors are taught by Kuchimanchi and when combined with Dumont, the limitation of claim 1 are met.
Applicant argues on pages 11-12, “D. The Cited Paragraphs Do Not Support the Rejection
Independently of the foregoing, the specific paragraphs the Examiner cites do not disclose what the rejection attributes to them. Applicant respectfully requests that, on reconsideration, the Examiner identify where in Kuchimanchi each proposition is actually disclosed as required by MPEP 2143.03. As noted above, the citations do not suggest the limitations the Office has ascribed to them. Therefore, the prima facie case is in error and the rejection in error. MPEP 2143
Applicant further notes that the rejection repeatedly characterizes Kuchimanchi as directed to "intravenous fluid delivery," "flow rate constants," and preventing "excess fluid delivery." Kuchimanchi is directed to dosing a therapeutic plasma protein (FVIII), not to intravenous fluid- volume management. The terminology in the rejection does not correspond to Kuchimanchi's actual disclosure, and the record does not establish that Kuchimanchi teaches the limitation for which it is cited.”
Applicant additionally argues that the language used in the rejection is not what is used in Kuchimanchi, however, the device of Kuchimanchi does not specifically use the language “intravenous fluid delivery”, “flow rate constant”, or “excess fluid delivery” but the structure and function of the device present has those properties, and the use of those words is proper.
As noted in the declaration of Farhad Jafari (filed herewith):
Applicant argues on pages 12-13, “5. The cited references address a different problem. I have reviewed Kuchimanchi (US 2020/0312436) and Dumont (US 2018/0296759). In my opinion, Kuchimanchi is directed to a fundamentally different problem from the one the claims address: it seeks to estimate the concentration of a drug in the blood and that objective belongs to the same broad family of approaches as the effective half-life methods used in nuclear medicine - for example, the single-time-point (Hanscheid) method and its multiple-time-point extensions - all of which estimate a concentration-time course rather than recover a patient's compartmental transport constants. I do not suggest that Kuchimanchi performs the Hanscheid method or uses that terminology; I refer to it only to identify the class of problem being solved.
6. Effective half-life methods do not apply to a compartmental model. None of the effective half-life methods on which such approaches rest applies to a compartmental model. The solution of a compartmental model is a sum of exponentials, and such a function does not possess a single effective half-life. A method that presumes a single effective half-life therefore cannot characterize a compartmental system.
7. Fitting exponentials is not the same as recovering rate constants. Some authors have proposed fitting multiple exponentials directly to measured data. That approach ignores the physiological interconnectedness of the compartments. In a compartmental model the eigenvalues of the transition matrix determine the exponents simultaneously for all compartments, whereas direct exponential fitting treats each compartment independently. I refer here deliberately to the exponents, and not to the rate constants.
8. Recovering the rate constants is a separate inverse problem. Recovering the underlying rate constants - that is, the transition probabilities between compartments - from those exponents is itself a separate and highly nontrivial inverse problem. It is not obtained merely by measuring concentrations over time, and it is not obtained by fitting an exponential decay.”
All of the above arguments are not supported directly by the claims. This may be the case, but what is stated in the limitations of claim 1 differs from the more complex mathematical teaching that is being presented above. It is not possible to read the half-life methods that applicant suggests from the specification or from other literature into the claims. Regarding the fitting of exponentials, the claims do not require the multiple exponential fitting described in the affidavit filed on 31 July 2026. The model that is presented in the prior art has multiple compartments as well exponent fitting with rate constant calculation which satisfies the claim limitations presented.
Applicant argues on pages 13-14, “E. The Rejection Does Not Establish an Adequate Reason to Combine
Even if the references collectively disclosed the claimed limitation (they do not), the rejection does not supply the articulated reasoning that a proper obviousness combination requires. An obviousness rejection "cannot be sustained by mere conclusory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness." KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007) (quoting In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006)).
The combination. Neither reference, alone or combined, computes a given patient's own transport rate constants or uses them to drive an infusion. Combining them would at most add an individualized weighting for how fast the protein leaves the blood on top of fixed population values - still not the patient's own transport rate constants the claims require. In my opinion a person of ordinary skill would have had no reasonable expectation of arriving at the claimed method from this combination.
Declaration of Farhad Jafari at pg. 2
14. The combination. Neither reference alone nor the two in combination derives a given patient's own compartmental transport rate constants or uses such constants to govern an infusion or to model the drug kinetics. Dumont supplies transport-to- active-site constants only as fixed population values; Kuchimanchi individualizes only a terminal-phase elimination exponent and contains no transport-to-active-site constant to individualize. Combining them would yield, at most, a population transport constant carrying an elimination-phase weighting, which is not the claimed derivation and use of the patient's own rate constants.
Declaration of Farhad Jarari at pg. 4-5.
Here, the articulated reason to combine collapses on its own predicate. The rejection's stated motivation is that "a patient's individual flow rates are used in a calculation for a delivery ... at a desired flow rate or flow constant," so that using individualized rates would "tailor[] the flow rate constants to an individual to provide the most optimized delivery possible and also prevent[] excess fluid delivery." The rejection expressly grounds that motivation in Kuchimanchi[0083]-[0086]. But as shown in Section III.D, [0083]-[0086] disclose only data-entry and sample-toggle user-interface screens - they say nothing about flow rate constants, individualized optimized delivery, or excess-fluid prevention. A motivation whose factual predicate is absent from the cited disclosure is not "articulated reasoning with ... rational underpinning"; it is a conclusion in search of support. KSR, 550 U.S. at 418; In re Kahn, 441 F.3d at 988.
The rejection separately asserts, without documentary support, that "[s]teady state infusion is well-known in the art and would be obvious to implement into the device of Dumont." That is a conclusory statement, unaccompanied by any reference or a proper statement of official notice, and it cannot supply a missing limitation or a rational basis to combine. See MPEP § 2144.03; KSR, 550 U.S. at 418.
Finally, the Examiner has not articulated why a person of ordinary skill would look to a population-based clotting-factor dosing tool to solve the problem of deriving and using an individual patient's own transport-to-active-site rate constants to set the delivery rate, nor why such a person would have a reasonable expectation of success in doing so - particularly where Kuchimanchi teaches that patient-specific determination is "complex or difficult ... without extensive blood draws" and for that reason resorts to a population model (Kuchimanchi[0063]). See In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). MPEP 2144 Establishing A Prima Facie Case
Applicant notes, secondarily, that Dumont operates by closed-loop control on real-time physiological feedback, whereas Kuchimanchi selects an intermittent regimen from a population model. To the extent the combination would import Kuchimanchi's feedforward population- dosing methodology into Dumont's feedback controller, it would alter Dumont's principle of operation. See In re Ratti, 270 F.2d 810 (CCPA 1959); MPEP § 2143.01(VI).
The reason to combine is stated in the rejection of claim 1, “modifying the device of Dumont to use individualized rates would improve the device by tailoring the flow rate constants to an individual to provide the most optimized delivery possible and also prevents excess fluid delivery (¶[0083]-[0086] from Kuchimanchi). Kuchimanchi also teaches that the model accounts for and allows for steady state functions (¶[0074]). Steady state infusion is well-known in the art and would be obvious to implement into the device of Dumont.” This is a statement of improvement of the device with stated paragraphs that list the way the device can improve Dumont. Additionally, this type of steady state infusion is well-known and combining different methods or approaches to a problem is a valid combination. The problem of “extensive blood draws” is different from the rate constant calculation as that is individualized data that can be used for rate constant calculation and the population based model is still a valid approach given the language and limitation of the claims as the individualized data is still present when creating said model.
Regarding claim 1, applicant argues neither Dumont nor Kuchimanchi teaches the calculation of a patent’s rate constants. Kuchimanchi specifically uses rate constants and models developed by the patient’s own data for operation. This updating of the model with data is a calculation of the rate constant as the values present will change based on the patient and the data that is being put back into the model. As applicant pointed out on page 8 of the arguments, Kuchimanchi specifically teaches the updating of a model with rate constants and the volume of distribution at steady-state which is a calculation and affirmation that steady-state delivery is occurring. The rate constant that is being calculated is not specified as anything but a rate constant. It is improper to read the specification or further define what is being calculated other than a rate constant which the limitation present in claim 1.
Applicant argues on page 15 that the combination in claim 1 does not teach the limitation, however, the limitation is not specific in the language that is needed for rate constants or steady-state infusion, but rather the language is broad and the device of Kuchimanchi does teach the limitation of the claim with Dumont. Furthermore, a person of ordinary skill in the art would recognize this field as being in the same area as the device in the application and the concepts such as calculating rate constants from patient data and having a steady-state fluid delivery would be well-known and an obvious step in combining.
Regarding claim 26, applicant argues on pages 15-16, the data collected from each patient and used in the calculation of a model that has rate constants is still the use of a bolus and the bolus data. This is taught in Kuchimanchi as established above due to the nature of the concentration calculation that occurs in the device.
Regarding claim 15, applicant argues on pages 16-17, as stated above, the claim does not specify how the rate constant must be calculated. The teaching of Kuchimanchi does take a population model but the rate constats are changed based on the patient’s own data and this is the limitation that is being claimed in the current application. This combination along with Russ teaches the necessary steady state infusion along with a model that takes into account patient data which results in a rate constant.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1, 2, 9-11, 14, 26-27 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Dumont et al. (US 2018/0296759) in view of Kuchimanchi (US 2020/0312436).
Regarding claim 1, Dumont and Kuchimanchi teach a method for steady state infusion of a drug (abstract, ¶[0092]) comprising:
calculating the rate constants of a patient for transport of a drug from an infusion site to an active site (¶[0041], where the rate constant of a patient is determined by said patient and thus why variability occurs);
creating a computer deliverable program that calculates the rate constants of the patient suited to control an infusion pump (¶[0033], where an MPC is designed for use in calculating rate constants, ¶[0048], where the rate constant of a patient is determined by said patient and thus why variability occurs);
providing an infusion pump (Fig. 1, 13) controllable by the computer deliverable program (¶[0048], where the pump 13 is controlled by controller 12 for the delivery process); and
delivering the drug to the patient via the infusion pump at a desired flow rate or flow constant (k) (¶[0048], where the controller 12 takes the constants calculated and directs the infusion pump 13 to deliver to the patient 14).
Dumont does not specifically teach delivering at a desired flow rate or flow constant as determined by said patient’s own rate constants identified in (i). Kuchimanchi teaches a system (Fig. 31, 102, 108, 112) including a processor (Fig. 31, 3104) with a visual display (Fig. 1, 3116). The device calculates the rate constants of a patient (¶[0061] & ¶[0143]). The processor is configured to update said constants for intravenous fluid delivery based on the individualized data from the patient in order to reach optimal rates (¶[0061]). The device of Kuchimanchi teaches that a patient’s individual flow rates are used in a calculation for a delivery of intravenous fluid at a desired flow rate or flow constant, therefore, modifying the device of Dumont to use individualized rates would improve the device by tailoring the flow rate constants to an individual to provide the most optimized delivery possible and also prevents excess fluid delivery (¶[0083]-[0086] from Kuchimanchi). Kuchimanchi also teaches that the model accounts for and allows for steady state functions (¶[0074]). Steady state infusion is well-known in the art and would be obvious to implement into the device of Dumont.
Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the device of Dumont to include have a processor that allows a device to deliver fluid at a desired flow rate or flow constant based on a patient’s own rate constants (¶[0061], [0083]-[0086], [0143] from Kuchimanchi).
Regarding claim 2, Dumont and Kuchimanchi teach the method of claim 1, Dumont further teaches wherein the delivery, via a needle, is intravenous or intramuscular (¶[0039], where the delivery methods include intravenous and intramuscular delivery).
Regarding claim 9, Dumont and Kuchimanchi teach discloses the method of claim 1, Dumont further teaches wherein an initial bolus of the drug is delivered providing kinetics for its steady state delivery (¶[0094], where an initial bolus reaches a steady state at a point after delivery).
Regarding claim 10, Dumont and Kuchimanchi teach the method of claim 1, Dumont further teaches wherein the computer deliverable program comprises a two-compartment model (¶[0036], where the MPC controller utilizes a PKPD model which is a multi-compartment model, which can include a two-compartment model).
Regarding claim 11, Dumont and Kuchimanchi teach the method of claim 1, Dumont further teaches wherein the computer deliverable program comprises a multi-compartment model (¶[0036], where the MPC controller utilizes a PKPD model which is a multi-compartment model).
Regarding claim 14, Dumont and Kuchimanchi teach the method of claim 2, Dumont further teaches wherein intramuscular means within the pectoralis, the gluteus, the calf, the rectus abdominus, the quadriceps or other muscle capable of accepting an intramuscular needle (¶[0039], where the intramuscular delivery method disclosed would include any muscle capable of accepting an intramuscular needle).
Regarding claim 26, Dumont and Kuchimanchi teach an apparatus for administering a steady-state infusion of a drug to a patient comprising:
a computer assisted infusion device (¶[0048], where the infusion pump 13 is controlled by an MPC controller);
a computer program designed to drive the infusion device (¶[0048]);
wherein the computer program calculates the rate constants of said patient from a first bolus(¶[0041]);
wherein the infusion device delivers a steady-state infusion of drug to said patient in proceeding bolus’ using said rate constants derived from said first bolus (¶[0094], where an initial bolus reaches a steady state at a point after delivery).
Dumont does not specifically teach wherein the computer program calculates the rate constants of said patient from a first bolus or wherein the infusion device delivers a steady-state infusion of drug to said patient in proceeding bolus’ using said rate constants derived from said first bolus.
Kuchimanchi teaches a system (Fig. 31, 102, 108, 112) including a processor (Fig. 31, 3104) with a visual display (Fig. 1, 3116). The device calculates the rate constants of a patient (¶[0061] & ¶[0143]). The processor is configured to update said constants for intravenous fluid delivery based on the individualized data from the patient in order to reach optimal rates (¶[0061]). The device of Kuchimanchi teaches that a patient’s individual flow rates are used in a calculation for a delivery of intravenous fluid at a desired flow rate or flow constant, therefore, modifying the device of Dumont to use individualized rates would improve the device by tailoring the flow rate constants to an individual to provide the most optimized delivery possible and also prevents excess fluid delivery (¶[0083]-[0086] from Kuchimanchi). Kuchimanchi also teaches that the model accounts for and allows for steady state functions (¶[0074]). Steady state infusion is well-known in the art and would be obvious to implement into the device of Dumont.
Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the device of Dumont to include have a processor that allows a device to deliver fluid at a desired flow rate or flow constant based on a patient’s own rate constants (¶[0061], [0083]-[0086], [0143] from Kuchimanchi).
Regarding claim 27, Dumont and Kuchimanchi teach the apparatus of claim 26, Dumont further teaches wherein the infusion device delivers the drug intravenously or intramuscularly (¶[0039], where the delivery methods include intravenous and intramuscular delivery).
Regarding claim 32, Dumont and Kuchimanchi teach the apparatus of claim 26, Dumont further teaches wherein the computer assisted infusion device infuses the drug with kinetics of a two-compartment model or a multi-compartment model (¶[0036], where the MPC controller utilizes a PKPD model which is a multi-compartment model).
Claim(s) 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Dumont et al. (US 2018/0296759) in view of Kuchimanchi (US 2020/0312436) as applied to claim 1 above, and further in view of Morgan (US 2024/0197652).
Regarding claim 3, Dumont and Kuchimanchi teach the method of claim 1, however, Dumont does not specifically teach wherein the drug is a serotonergic drug.
Dumont teaches different types of drugs that are able to be used in the device such as hypnotics (the infusion device and the controller of Dumont have the capability to delivery other drugs including: analgesics, neuro-muscular blockers, hemodynamics and others, ¶[0011]). Morgan teaches a serotonergic agent that affects a serotonin receptor (¶[0326]). The device of Dumont already has a wide breadth of drugs that can be utilized in the device and by modifying the device of Dumont with the drugs used in Morgan, it would not only provide a wider array of drugs that can be infused, but because it is a serotonergic agent it would block or influence reactions at the receptors (¶[0326] from Morgan).
Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the device of Dumont to use a serotonergic drug in an intramuscular injection (¶[0326] from Morgan).
Regarding claim 4, the combination of Dumont, Kuchimanchi and Morgan teaches he method of claim 3, Morgan further teaches wherein the serotonergic drug is a psychedelic drug (¶[0327]).
Claim(s) 6, 8, 28, and 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Dumont et al. (US 2018/0296759) in view of Kuchimanchi (US 2020/0312436) as applied to claim 1 above, and further in view of in view of Haider et al. (US 2005/0245895).
Regarding claim 6, Dumont and Kuchimanchi teach the method of claim 2, however, Dumont does not specifically disclose wherein the needle comprises a number of side holes ranging from 1-100.
Haidar teaches a device for epidermal or intradermal delivery including a needle. Haidar teaches a needle shaft (Fig. 1b, 11) comprising side holes (Fig. 1b, 19). Modifying the device of Dumont to include a needle that includes side holes would allow for the delivery of a substance at various depths shallower than the length of the needle shaft (¶[0040] from Haidar).
Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the device of Dumont to include a needle shaft (Fig. 1b, 11 from Haidar) that has side holes that range from 1-100 (Fig. 1b, 19 from Haidar).
Regarding claim 8, Dumont and Kuchimanchi teach the method of claim 2, Haidar further teaches wherein the needle comprises curve at the base of the needle ranging from 0 to 90 degrees (Fig. 1b, 11, where the angle of the curve would be considered 0 as the needle is straight).
Regarding claim 28, Dumont and Kuchimanchi teach the apparatus of claim 27, Haidar further teaches wherein intramuscular infusion comprises a modified needle.
Haidar teaches a device for epidermal or intradermal delivery including a needle. Haidar teaches a needle shaft (Fig. 1b, 11) comprising side holes (Fig. 1b, 19). This is a modification of a traditional needle. Modifying the device of Dumont to include a needle that includes side holes would allow for the delivery of a substance at various depths shallower than the length of the needle shaft (¶[0040] from Haidar).
Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the device of Dumont to include a needle shaft (Fig. 1b, 11 from Haidar) that has side holes that range from 1-100 (Fig. 1b, 19 from Haidar) and have a modified needle.
Regarding claim 30, Dumont and Kuchimanchi teach the apparatus of claim 28, Haidar further teaches wherein the needle (Fig. 1b, 11) comprises a number of side holes ranging from 2-100 (Fig. 1b, 19).
Regarding claim 31, Dumont and Kuchimanchi teach he apparatus of claim 28, Haidar further teaches wherein the needle comprises a curve at the base of the needle ranging from 0 to 90 degrees (Fig. 1b, 11, where the angle of the curve would be considered 0 as the needle is straight).
Claim(s) 15 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Dumont et al. (US 2018/0296759) in view of Kuchimanchi (US 2020/0312436) as applied to claim 1 above, and further in view of in view of Russ et al. (US 2020/0147038).
Regarding claim 15, Dumont teaches a steady state concentration of a psychotropic compound as determined by each patient’s rate constant (¶[0011], where the drug is hypnotic and is therefore psychotropic, [0094], where an initial bolus reaches a steady state, and a patient’s rate constant will vary as shown by the data samples in Dumont making each rate constant substantially different based on that patient)
wherein the steady state concentration is maintained by a computer controlled infusion pump (where the controller 12 is an MPC controller that interacts with the pump 13 and maintains the desired amount of infused drug);
wherein the infusion pump maintains the steady state concentration according to two compartment or multi-compartment kinetics (¶[0036], where the MPC controller utilizes a PKPD model which is a multi-compartment model).
Kuchimanchi teaches a system (Fig. 31, 102, 108, 112) including a processor (Fig. 31, 3104) with a visual display (Fig. 1, 3116). The device calculates the rate constants of a patient (¶[0061] & ¶[0143]). The processor is configured to update said constants for intravenous fluid delivery based on the individualized data from the patient in order to reach optimal rates (¶[0061]). The device of Kuchimanchi teaches that a patient’s individual flow rates are used in a calculation for a delivery of intravenous fluid at a desired flow rate or flow constant, therefore, modifying the device of Dumont to use individualized rates would improve the device by tailoring the flow rate constants to an individual to provide the most optimized delivery possible and also prevents excess fluid delivery (¶[0083]-[0086] from Kuchimanchi). Kuchimanchi also teaches that the model accounts for and allows for steady state functions (¶[0074]). Steady state infusion is well-known in the art and would be obvious to implement into the device of Dumont.
Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the device of Dumont to include have a processor that allows a device to deliver fluid at a desired flow rate or flow constant based on a patient’s own rate constants (¶[0061], [0083]-[0086], [0143] from Kuchimanchi).
Dumont does not specifically disclose a method of treating a mental health complaint comprising administering to a patient in need thereof.
Russ teaches a method of treating a mental health complaint comprising administering to a patient in need thereof (¶[0003]). It would have been obvious to one of ordinary skill in the art prior to the effective filing date to modify the device of Dumont to treat a mental health complaint comprising administering to a patient in need the device of Dumont would be improved by directly treating the complaint in a wide variety of areas such as anxiety, depression or addiction (¶[0003], [0146], [0156] from Russ).
Regarding claim 18, Dumont, Kuchimanchi and Russ teach the method of claim 15, Dumont further teaches wherein the psychotropic compound is administered intravenously or intramuscularly (¶[0011], where the hypnotic agent is psychotropic, ¶[0039], where the delivery methods include intravenous and intramuscular delivery from Dumont).
Claim(s) 16 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Dumont et al. (US 2018/0296759) in view of Kuchimanchi (US 2020/0312436) as applied to claim 1 above, and further in view of in view of Russ et al. (US 2020/0147038), and further in view of Tsibulsky (“Real time computation of in vivo drug levels during drug self-administration experiments”, NIH Public Access, 2005 May).
Regarding claim 16, the combination of Dumont, Kuchimanchi and Russ teaches the method of claim 15, however, Dumont, Kuchimanchi and Russ do not specifically teach wherein the kinetics is first order.
Tsibulsky teaches an administration program utilizing self-administration and pharmacokinetic properties. In particular Tsibulsky teaches there is a choice between first or second-order processes and uses a two or three-compartment model similar to the device used in Dumont. The first or second order of kinetics used is known in the art to be used in devices that utilize controllers and have multi-compartment models as demonstrated by the article by Tsibulsky (abstract). Kuchimanchi teaches that the models used in the device are first-order and when combined with Dumont gives the device rate constants associated with patient’s.
Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to utilize first order kinetics in the device of Dumont based on known pharmacokinetics as evidenced by the abstract of Tsibulsky.
Regarding claim 17, the combination of Dumont, Kuchimanchi and Russ teaches he method of claim 15, however, Dumont, Kuchimanchi and Russ do not specifically teach wherein the kinetics is second order.
Tsibulsky teaches an administration program utilizing self-administration and pharmacokinetic properties. In particular Tsibulsky teaches there is a choice between first or second-order processes and uses a two or three-compartment model similar to the device used in Dumont. The first or second order of kinetics used is known in the art to be used in devices that utilize controllers and have multi-compartment models as demonstrated by the article by Tsibulsky (abstract).
Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to utilize second order kinetics in the device of Dumont based on known pharmacokinetics as evidenced by the abstract of Tsibulsky.
Conclusion
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HADEN M RITCHIE whose telephone number is (703)756-1699. The examiner can normally be reached M-F 8am-5:30pm.
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/HADEN MATTHEW RITCHIE/Examiner, Art Unit 3783
/BHISMA MEHTA/Supervisory Patent Examiner, Art Unit 3783
