DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-25 are presented for examination.
Claims 1-25 are rejected under 35 USC 101.
Claims 1,8-12 , 14 and 21-25 are rejected under 35 U.S.C. 103 as being unpatentable over Li, Y., and Y. Chen. "Modeling in pharmaceutical packaging." Predictive Modeling of Pharmaceutical Unit Operations. Woodhead Publishing, 2017 in the view of Carstensen, Jens T. "Stability of Drugs and Drug Products in Clinical Packaging." DRUGS AND THE PHARMACEUTICAL SCIENCES 87 (1998):
Claims 2-3 and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Li, Y., and Y. Chen. "Modeling in pharmaceutical packaging." Predictive Modeling of Pharmaceutical Unit Operations. Woodhead Publishing, 2017 in the view of Carstensen, Jens T. "Stability of Drugs and Drug Products in Clinical Packaging." DRUGS AND THE PHARMACEUTICAL SCIENCES 87 (1998) further in the view of Ravnik, J., et al. "Lyophilization model of mannitol water solution in a laboratory scale lyophilizer." Journal of drug delivery science and technology 45 (2018):
Claims 4-5 and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Li, Y., and Y. Chen. "Modeling in pharmaceutical packaging." Predictive Modeling of Pharmaceutical Unit Operations. Woodhead Publishing, 2017 in the view of Carstensen, Jens T. "Stability of Drugs and Drug Products in Clinical Packaging." DRUGS AND THE PHARMACEUTICAL SCIENCES 87 (1998) further in the view of Mascarenhas, W. J., H. U. Akay, and M. J. Pikal. "A computational model for finite element analysis of the freeze-drying process." Computer methods in applied mechanics and engineering 148.1-2 (1997):
Claims 6 -7 ,13 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Li, Y., and Y. Chen. "Modeling in pharmaceutical packaging." Predictive Modeling of Pharmaceutical Unit Operations. Woodhead Publishing, 2017 in the view of Carstensen, Jens T. "Stability of Drugs and Drug Products in Clinical Packaging." DRUGS AND THE PHARMACEUTICAL SCIENCES 87 (1998) further in the view of Corveleyn, Sam, Stefaan De Smedt, and Jean Paul Remon. "Moisture absorption and desorption of different rubber lyophilisation closures." International journal of pharmaceutics 159.1 (1997):
This action is Non-final rejection.
Priority
Acknowledgment is made for a domestic priority date of PCT/US2021/048181 on 08/30/2021 which claims benefit of PRO application 63/075956 filing date 09/09/2020.
Information Disclosure Statement
The IDS filed on 03/08/2023, 07/25/2025, 12/01/2025, 12/02/2025 and 01/21/2026 are reviewed ad considered. See the attached files.
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 1-25 are rejected under 35 U.S.C. 101 because the claimed invention is directed to mental process without any additional elements that provides a practical application or amount to significantly more than the abstract idea.
Step 1: Yes: The claims 1-25 are drawn to a method and system, which falls under a process of a statutory category of the invention.
Step 2A: Prong 1: Yes The claim 1 limitation recites (bolded for abstract idea identification):
Regarding claim 1 and 14:
A method of computational modeling to predict stability of a lyophilized drug product, the method comprising: this claim is not directed to a computer implemented method using a specific computer implemented tool to predict the stability of a lyophilized drug product, so under BRI this can be performed by a human mind by performing observation, analyzing, evaluation and judgment with the help of pencil and paper. Therefore it is an abstract idea under mental process.
receiving, by processing hardware of a computing system, model parameters describing a virtual cake, a virtual vial, a virtual stopper, and a virtual ambient environment; (insignificant extra-solution activity – data gathering, such as 'outputting
data'. See MPEP 2106.05(g).)
computing, by the implementing a computational model and at each of a plurality of virtual time steps, a change in water amount or concentration in each of (i) the virtual cake, (ii) virtual air within the virtual vial, and (iii) the virtual stopper, wherein computing the changes in water amount or concentration includes applying the model parameters to the computational model; (This claim recites computing of water amount or concentration on the gathered information and it does not specify any specific computer implemented tool to perform this but according to [0027], computing of concentration is performed using a mathematical equation. A human mind can compute water amount or concentration using a pencil and paper by applying the model parameters into the equation. Therefore it is an abstract idea under mental process.).
generating, by the , information for display to a user via a , the information being indicative of at least the water amount or concentration of the virtual cake at one or more time steps of the plurality of virtual time steps (this claim recites abstract idea under mental process. Under BRI, a human mind can generate information of water amount. As it is recited on the above claim limitation a water amount is computed using a mathematical equation, so using those information a human can draw a graph of water amount vs time to display for the user using pencil and paper).
Step 2A Prong 2: No
The claims do not recite additional elements that integrate the exception into a
practical application of the exception because the claim do not have additional elements or a combination of additional elements that apply, rely on, or use the judicial exception in a manner that impose a meaningful limit on the judicial exception.
Claims recites gathering data which is insignificant extra solution activity. Adding
insignificant extra-solution activity to the judicial exception, e.g., mere data gathering in conjunction with a law of nature or abstract idea such as a step of obtaining information about credit card transactions so that the information can be analyzed by an abstract mental process, as discussed in CyberSource V. Retail Decisions, Inc., 654 F.3d 1366, 1375, 99 USPQ2d 1690, 1694 (Fed. Cir. 2011) (see MPEP § 2106.05(g),
receiving, by processing hardware of a computing system, model parameters describing a virtual cake, a virtual vial, a virtual stopper, and a virtual ambient environment; (insignificant extra-solution activity – data gathering, such as such as 'obtaining information'. See MPEP 2106.05(g).)
Claim 1 recites additional element of “processing hardware” and “user interface” but it is merely using of a software, or computer component, to implement abstract idea without making improvement in the software or the computer itself merely used as a tool and it does not make improvement to the functioning of the additional elements, see MPEP 2106.05(a), Improvements to the Functioning of a Computer or To Any Other Technology or Technical Field [R-07.2022]).
Claim 14, in addition to the above additional element recited on claim 1. It also recites “computing system comprising: processing hardware; and one or more memories storing instructions that, when executed by the processing hardware, cause the computing system to perform the process”., but this additional elements are merely used as a tool to perform the abstract idea with out any specific hardware or software in the computer system and improvement to the computer system is not claimed as it is explained above on claim 1. Therefore claim 14 is also not eligible under 35 USC 101, under the same rational as of claim 1.
Step 2B: NO
The claim do not recite additional elements which are significantly more than the abstract idea. As out lined above on Step 2A prong 2, the claim merely use a computer components, hardware to obtain information and to perform abstract idea. Merly using of a computer, software or manufacturing machine and applying abstract ideas into a system without making improvement to the functionality of a computer, software or manufacturing machine is not a significantly more.
Regarding dependent claims
Claim 2 and 15:
‘wherein computing the changes in water amount or concentration further includes: applying boundary conditions (i) between an external surface of the virtual stopper and the virtual ambient environment, (ii) between an internal surface of the virtual stopper and the virtual air, and (iii) between the virtual air and the virtual cake”. This further add details to abstract idea (mental step) based on observation, evaluation. Judgement to assign a boundary condition on each of the gathered information.
Claim 3 and 16:
“wherein applying the boundary conditions includes computing partition coefficients using function representations of one or both of: a stopper-air sorption and/or desorption moisture isotherm; and a cake-air sorption and/or desorption moisture isotherm” This also further add detail to the abstract idea (mental step) based on observation, evaluation and judgment to compute partial coefficient based on the equation on [0027], so a human can perform computing of coefficient using pencil and paper.
Claim 4 and 17:
“wherein the computational model is a finite-element analysis (FEA) model, such that computing the changes in water amount or concentration includes computing, at each of at least some of the plurality of virtual time steps, a water amount or concentration and a water mass flux for each of a plurality of discrete spatial elements within the virtual cake, the virtual air, and the virtual stopper” This claim also add details to the abstract idea (mental process) and further narrow the claim. A human mind can perform computing change in water amount or concentration and mass flux using mathematical/ physics concepts on a specific partition by using parameters of each grid with the aid of pencil and paper.
Claim 5 and 18 :
“wherein the FEA model is a two-dimensional axisymmetric model that assumes symmetric vial and stopper configurations” This step also further defines abstract idea of claim 1, the claim does not disclose any additional limitations that integrate the judicial exception into practical element.
Claim 6 and 19:
“wherein the model parameters include geometries of the virtual vial and the virtual stopper” it further defines the type of data obtained. (insignificant extra-solution activity – data gathering, such as such as 'obtaining information'. See MPEP 2106.05(g).) and It doesn’t disclose any additional limitations that integrate the judicial exception into practical application.
Claim 7 and 20:
“wherein the model parameters include one or more of: a moisture diffusivity coefficient of the virtual stopper; a density of the virtual stopper; or a starting water amount or concentration of the virtual stopper” ” it further defines the type of data obtained - (insignificant extra-solution activity – data gathering, such as such as 'obtaining information'. See MPEP 2106.05(g).) and It doesn’t disclose any additional limitations that integrate the judicial exception into practical application
Claim 8 and 21:
“wherein the model parameters include one or both of: a starting weight and/or density of the virtual cake; and a starting water amount or concentration of the virtual cake” . it further defines the type of data obtained-(insignificant extra-solution activity – data gathering, such as such as 'obtaining information'. See MPEP 2106.05(g).) and It doesn’t disclose any additional limitations that integrate the judicial exception into practical application.
Claim 9 and 22:
“wherein the model parameters include one or both of: a temperature of the virtual ambient environment; and a humidity of the virtual ambient environment”. it further defines the type of data obtained-(insignificant extra-solution activity – data gathering, such as such as 'obtaining information'. See MPEP 2106.05(g).) and It doesn’t disclose any additional limitations that integrate the judicial exception into practical application.
Claim 10 and 23:
“wherein the information is indicative of the water amount or concentration of the virtual cake as a function of time” this further narrow the abstract idea (mental process). A human mind can draw a graph of a function of time by making observation/ evaluation using a pencil and paper.
Claim 11 and 24:
“wherein the information is indicative of a change in weight of the virtual cake” this further narrow the abstract idea (mental process). A human mind can draw a graph of change in weight of the cake by making observation/ evaluation using a pencil and paper.
Claim 12 and 25:
“wherein the information is indicative of whether the water amount or concentration of the virtual cake at a particular time step, or steps, of the plurality of virtual time steps satisfies one or more stability criteria associated with the lyophilized drug product”. This add details on the abstract idea (mental process). A human mind with a pencil and paper can compare the computed water amount or concentration with the stabilized criteria and using human observation/ evaluation/ judgment skill, we can decide if the drug satisfies the criteria in each time step to be stable.
Claim 13:
“using the displayed information to select one or more of: a stopper type to use for the lyophilized drug product; a vial type to use for the lyophilized drug product; an ambient environment temperature to maintain for the lyophilized drug product; an ambient environment humidity to maintain for the lyophilized drug product; or a stopper drying target” This further add details to the abstract idea(mental process). A human mind can observe the displayed information and select any of the above listed specification about the obtained information.
As it was analyzed above the dependent claims also field to recite additional elements which are significantly more than the abstract ideas and the claims does not recite additional elements or a combination of additional elements that apply, rely on, or use the judicial exception in a manner that impose a meaningful limit on the judicial exception.
Therefore, it is concluded that the claims 1-25 are not found eligible under 35 USC 101.
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
Claims 1,8-12 , 14 and 21-25 are rejected under 35 U.S.C. 103 as being unpatentable over Li, Y., and Y. Chen. "Modeling in pharmaceutical packaging." Predictive Modeling of Pharmaceutical Unit Operations. Woodhead Publishing, 2017 in the view of Carstensen, Jens T. "Stability of Drugs and Drug Products in Clinical Packaging." DRUGS AND THE PHARMACEUTICAL SCIENCES 87 (1998):
As of claim 1, Li teaches A method of computational modeling to predict stability of a lyophilized drug product, the method comprising: (page 317, Drug product shelf life is determined based on the time scale over which a product remains chemically and physically stable. Product stability depends on the chemical property of the drug substance, formulation, and the environmental conditions for storage such as temperature, oxygen, and moisture, … There may be multiple approaches to stabilize a product. The discussion of this chapter will be limited to the topic of moisture protection for solid pharmaceutical products).
receiving, by processing hardware of a computing system, model parameters describing a virtual cake, a virtual vial, and a virtual ambient environment; (page 326 , Moisture uptake of packaged product in storage is governed by several factors such as container WVTR, (virtual vial) moisture sorption isotherm, environmental condition, packaging configuration, and initial moisture content of the packaged product.( virtual ambient environment). The rate of moisture permeation through a container usually decreases over time as the humidity in the container increases due to the accumulation of moisture in the container. Page 317, “Introduction” The discussion of this chapter will be limited to the topic of moisture protection for solid pharmaceutical products. (virtual cake).
generating, by the processing hardware, information for display to a user via a user interface, the information being indicative of at least the water amount or concentration of the virtual cake at one or more time steps of the plurality of virtual time steps (page 335, The proposed commercial package for the new strengths of tablets is 30 tablets per 3-ounce HDPE bottle with 3 g silica gel. There will be no cotton used in the package. Fig. 12.8 shows that with initial tablet moisture content as high as 2.0%
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the moisture content in the packaged tablets stored at 25C/60%RH will be less than 1.1% during storage. The modeling data indicates that the proposed commercial packaging system is suitable for maintaining acceptable product stability over 2 years).
Li does not explicitly teach a virtual stopper and computing, by the processing hardware implementing a computational model and at each of a plurality of virtual time steps, a change in water amount or concentration in each of (i) the virtual cake, (ii) virtual air within the virtual vial, and (iii) the virtual stopper, wherein computing the changes in water amount or concentration includes applying the model parameters to the computational model;
While Carstensen teaches a virtual stopper (page 234,
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computing, by the processing hardware implementing a computational model and at each of a plurality of virtual time steps, a change in water amount or concentration in each of (i) the virtual cake, and (iii) the virtual stopper, wherein computing the changes in water amount or concentration includes applying the model parameters to the computational model; (page 234, General, however, is interaction with the closure. Consider a vial, such as shown in Fig. la.( as shown above), This type of system is considered a two-phase system, considering the plug (in this case) one phase (denoted “l”), and the solution the other phase (denoted “2”). In such systems, the law of partition requires that:
C1= KC2
where K is the partition coefficient, and C? and C, are the respective concentrations.
When the product is first made, C, is zero and C, is the initial concentration of drug in the dosage form. It will be assumed in the example to follow that the drug is chemically stable, and that the volume of the plug is V, and that of the solution is V?. The original amount of drug in solution is M, grams, and after equilibrium it is M* grams so that M, - M* grams have been transferred to the plug. Hence, dividing these two amounts by the respective volumes:
M*/V, = K(M, - M*)/V, (2)
Only K is unknown and once M* (or rather C* = M*/V2) is determined then K may be found. A good example of this is the work by Mendenhall (Fig. This type of behavior is first order (actually equilibrium kinetics), and if 2). the concentration, C. is transformed in the following fashion:
In[C - C*] = -kt + In[C, - C*] (3)
then a straight line is obtained (Fig. 3). k is here the sum of the absorption and desorption rate constants as in conventional equilibrium kinetics). As it is recited above concentration for the virtual cake “C2” and the concentration for the virtual stopper “C1” is computed a parameters like volume and mass of drug and container is also applied.
(ii) virtual air within the virtual vial, (page 246,
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The situation of moisture transfer from a vapor pressure of P, on the outside of the bottle to the inside, where the pressure is denoted P, is depicted in Fig. 13. The situation refers to a blister as well, except here the closure would be the seal. Diffusion of a gas (e.g., water vapor) through a film of thickness, h, and diffusion coefficient, D, is given by Eq. 13 and equating this with Eq. 18:
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The solid possesses a specific moisture isotherm, and in the simplest of the Peppas models (14), it is assumed that this is simply a linear function (Fig. 14).
P2 = QX
where Q is a constant and x is g of moisture per g of solid. Hence: ….). As it is cited above p2 is mapped with the virtual air within the container as it is shown on figure 13.
Li and Carstensen is considered to be analogous to the claimed invention, since they focus on freeze drying of drug products. Therefore it would be obvious for a person of ordinary skill in the art , before the effective filling date to combine Li teaching of modeling in pharmaceutical packaging using a drug in a container and analyses and show the amount of water content within time using graph, with Carstensen teaching of using a stopper and computing the concentration or change water amount on the cake, stopper and the air inside the vial using the model parameters like mass and volume.
The motivation would have been to accurately predict moisture content of pack aged product during storage using the polynomial moisture uptake model and this prediction methods can be used to design formulations, evaluate the selected packaging materials, design packaging configurations, and determine the appropriate amount of desiccant and cotton to be used for a product (Li, page 339 -340). The design model should also be following the Drug Administration (FDA) packaging requirements so by integrating Carstensen teaching of stability of Drugs and Drug Products in Clinical Packaging to create proper packaging and accurate stability time (Carstensen, page 232).
Claim 14, is also in the same scope as claim 1 with additional elements of a computer system including processing hardware, and memories to store instruction, while Li performs simulation and it also use software (page 328), so it is obvious that a computer is used to perform simulation or to use the software, and computer inherently have a memory and processor.
Therefore claim 14, is also rejected under the same rational as of claim 1.
As of claim 8, the modified model teaches all the limitations of claim 1, and Li also teaches wherein the model parameters include one or both of: a starting weight and/or density of the virtual cake; and a starting water amount or concentration of the virtual cake (page 331, weights of tablet(cake)
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Claim 21 is also in the same scope as that of claim 8, therefore claim 21, is rejected under the same rational as claim 8.
As of claim 9, the modified model teaches all the limitations of claim 1, and Li also teaches wherein the model parameters include one or both of: a temperature of the virtual ambient environment; and a humidity of the virtual ambient environment.(page 317, Product stability depends on the chemical property of the drug substance, formulation, and the environmental conditions for storage such as temperature, oxygen, and moisture and Table 12.1 Moisture permeability of HDPE bottles).
Claim 22 is also in the same scope as that of claim 9, therefore claim 22, is rejected under the same rational as claim 9.
As of claim 10, the modified model teaches all the limitations of claim 1, and Li also teaches wherein the information is indicative of the water amount or concentration of the virtual cake as a function of time (page 335,
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Claim 23 is also in the same scope as that of claim 10, therefore claim 23, is rejected under the same rational as claim 10.
As of claim 11, the modified model teaches all the limitations of claim 1, and Li also teaches wherein the information is indicative of a change in weight of the virtual cake (page 331,
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Claim 24 is also in the same scope as that of claim 11, therefore claim 24, is rejected under the same rational as claim 11.
As of claim 12 the modified model teaches all the limitations of claim 1, and Li also teaches wherein the information is indicative of whether the water amount or concentration of the virtual cake at a particular time step, or steps, of the plurality of virtual time steps satisfies one or more stability criteria associated with the lyophilized drug product.(page 329, Four tablet formulations with different dose strength (listed in Table 12.4) were developed and manufactured. Tablet A is a marketed product and is used as a reference in the study. Tablets B, C, and D are new strengths developed for post marketing application. A new drug application (NDA) stability study on the reference Tablet A packaged in 1-ounce HDPE bottle (3 tablets with 1.1 g silica gel and 9 g cotton) showed that the total moisture content in the packaged tablets is about 1.1% after 6 months storage under 40C/75%RH condition and the product still remains acceptable. Therefore, 1.1% moisture content in tablets is used as a criterion for packaging selection to ensure acceptable shelf life is achieved for the new strengths of tablets).
Claim 25 is also in the same scope as that of claim 12, therefore claim 25, is rejected under the same rational as claim 12.
Claims 2-3 and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Li, Y., and Y. Chen. "Modeling in pharmaceutical packaging." Predictive Modeling of Pharmaceutical Unit Operations. Woodhead Publishing, 2017 in the view of Carstensen, Jens T. "Stability of Drugs and Drug Products in Clinical Packaging." DRUGS AND THE PHARMACEUTICAL SCIENCES 87 (1998) further in the view of Ravnik, J., et al. "Lyophilization model of mannitol water solution in a laboratory scale lyophilizer." Journal of drug delivery science and technology 45 (2018):
As of claim 2, the modified model teaches all the limitation of claim 1, but it doesn’t explicitly teach applying boundary conditions ; i) between an external surface of the virtual stopper and the virtual ambient environment, (ii) between an internal surface of the virtual stopper and the virtual air, and (iii) between the virtual air and the virtual cake.
While Ravnik teaches wherein computing the changes in water amount or concentration further includes: applying boundary conditions (abstract
The effects of the small scale of the laboratory device with respect to a correct definition of boundary conditions for the numerical simulations are described, especially the effect of the comparatively high temperatures of the chamber walls. In the numerical model, a 1D vial approximation of the governing equations of heat and mass transport with moving front between the frozen and porous part of the cake is used and solved in a time stepping nonlinear iteration procedure).
(i),between an external surface of the virtual stopper and the virtual ambient environment, (page 31, 34, the heat transfer to the vial was not only influenced by temperature conditions of the shelves, but also by the temperature conditions at the walls … The overall heat flux density q˙ is proportional to the overall heat transfer coefficient U and temperature difference between the boundary condition of the shelf or wall Tbc and vial temperature Tv
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The virtual ambient environment is the external environment and vial temperature and the temperature condition by the wall is mapped to the external surface of the virtual stopper.
(ii) between an internal surface of the virtual stopper and the virtual air, and (Page 33, To get the molar flux, integration is needed from the sublimation surface (p v ,0 = p * v ) to the top of the vial with conditions of the free space of the lyophilized drying chamber(p vh, )
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Page 34 .For the edge vial, the side wall effect was taken into account at the top surface by using a modified temperature boundary condition, set to the average temperature of the gas, thechambersidewallsandtheshelf,seeFig.3).
(iii) between the virtual air and the virtual cake ( Page 30, In the first drying stage, in the vial there coexist a frozen part of the cake (Region 2) in contact with a porous, ice-free part of the cake (Region 1), Fig. 1. Both regions are connected by a sublimation front, where drying of the frozen solvent (water) takes place under sublimation conditions… The main driving force of sublimation is the pressure difference between the vapor pressure at the sublimation front and partial vapor pressure in the surroundings of the vial).
Ravnik is considered to be analogous to the claimed invention, because it teaches development of a numerical model for the simulation of a lyophilization process in a vial. Therefore it would be obvious to try for a person of ordinary skill in the art, before the effective filling date to apply boundary condition on each of the above limitations based on Ravnik’s teaching of applying boundary condition for the numerical model to compute the changes in water amount or concentration according to the modified model.
The motivation would have been by applying a boundary conditions on the temperatures of the inner walls of the drying chamber and, in the case of the vials at the tray edges, a modified bulk temperature definition was included into the model of boundary conditions in order to create fast and accurate computational tool for prediction of lyophilization dynamics, and can also be included into a general 3D CFD computational framework as a vital part of the final virtual lyophilized model.
Claim 15 is also in the same scope as that of claim 2, therefore claim 15, is rejected under the same rational as claim 2.
As of claim 3, the modified model teaches all the limitations of claim 2, and Li also teaches wherein applying the boundary conditions includes computing partition coefficients using function representations of one or both of: a stopper-air sorption and/or desorption moisture isotherm; and a cake-air sorption and/or desorption moisture isotherm. (Li 322 and page 325 figure 12.2, In practice, water concentration on the outer surface of the container wall, C0, is not measured. Instead, C0 can be assumed to be proportional to the equilibrium external water concentration in the air Cair by partition theory, as shown in
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where K is the partition coefficient of water vapor in the container wall material, Pa and Ps (Pa) are the actual and the saturated water vapor pressure in the air at temperature T, respectively, R is the gas constant, and %RH is the percent relative humidity). As it cited above the equation 12.7 shows stopper -air sorption, since C0 is considers as stopper concentration (water concentration on the outer surface of the container wall ) and C air as air concentration.
Claim 16 is also in the same scope as that of claim 3, therefore claim 16, is rejected under the same rational as claim 3.
Claims 4-5 and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Li, Y., and Y. Chen. "Modeling in pharmaceutical packaging." Predictive Modeling of Pharmaceutical Unit Operations. Woodhead Publishing, 2017 in the view of Carstensen, Jens T. "Stability of Drugs and Drug Products in Clinical Packaging." DRUGS AND THE PHARMACEUTICAL SCIENCES 87 (1998) further in the view of Mascarenhas, W. J., H. U. Akay, and M. J. Pikal. "A computational model for finite element analysis of the freeze-drying process." Computer methods in applied mechanics and engineering 148.1-2 (1997):
As of claim 4, the modified model teaches all the limitations of claim 1, but it does not explicitly teach wherein the computational model is a finite-element analysis (FEA) model, such that computing the changes in water amount or concentration includes computing, at each of at least some of the plurality of virtual time steps, a water amount or concentration and a water mass flux for each of a plurality of discrete spatial elements within the virtual cake, the virtual air, and the virtual stopper.
While Mascarenhas teaches wherein the computational model is a finite-element analysis (FEA) model, such that computing the changes in water amount or concentration includes computing, at each of at least some of the plurality of virtual time steps, a water amount or concentration and a water mass flux for each of a plurality of discrete spatial elements within the virtual cake, the virtual air, and the virtual stopper (Abstract A brief overview of the freeze-drying formulation in two-dimensional axisymmetric space. The model calculates the time wise variation of the partial pressure of water vapor, the temperature, and the concentration of sorbed water … Page 119, The variation of the sorbed water concentration at seven different locations along r = 0.5 cm is shown in Fig. 16. The water concentration along the thickness of the sample at three different cross-sections (r = 0.0, r = 0.5 cm, r = 1.0 cm) is shown in Fig. 17. The solution obtained at the end of the primary drying analysis was used as the initial condition for the secondary analysis… Page 120, The flux dependence of the water vapor pressure is given by the following equations:
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) as it is cited above FEA model is used to compute the concentration of sorbed water, molar flux as mass flux for each of a plurality of discrete spatial elements.
Mascarenhas is considered to be analogous to the claimed invention because it teaches a computational model for finite element analysis of the freeze-drying process. Therefore it would be obvious to try by a person of ordinary skill in the art, before the effective filling date to apply a FEA method based on the Mascarenhas teaching to compute concentration and mass flux of each partial elements on the teaching of the modified model’s virtual cake, virtual air, and virtual stopper.
The motivation would have been by using the governing equation and the finite element formulation in two-dimensional axisymmetric space used to calculate the time wise variation of the partial pressure of water vapor, the temperature and concentration of sorbed water in order to preserve the product quality overtime (Mascarenhas, 106-107).
Claim 17 is also in the same scope as that of claim 4, therefore claim 17, is rejected under the same rational as claim 4.
As of claim 5, the modified model teaches all the limitations of claim 4, and Mascarenhas also teaches wherein the FEA model is a two-dimensional axisymmetric model that assumes symmetric vial and stopper configurations (Page 119 , A 18 X 11 mesh was used for the analysis. The finite element mesh along with the boundary conditions is shown in Fig. 12. The material was freeze-dried in a cylindrical vial of radius 1 cm. The material thickness is 2 cm. A two-dimensional axisymmetric interface position analysis was performed to simulate the freeze-drying process. An initial of 0.04 cm was used to properly start the analysis).
Claim 18 is also in the same scope as that of claim 5, therefore claim 18, is rejected under the same rational as claim 5.
Claims 6 -7 ,13 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Li, Y., and Y. Chen. "Modeling in pharmaceutical packaging." Predictive Modeling of Pharmaceutical Unit Operations. Woodhead Publishing, 2017 in the view of Carstensen, Jens T. "Stability of Drugs and Drug Products in Clinical Packaging." DRUGS AND THE PHARMACEUTICAL SCIENCES 87 (1998) further in the view of Corveleyn, Sam, Stefaan De Smedt, and Jean Paul Remon. "Moisture absorption and desorption of different rubber lyophilisation closures." International journal of pharmaceutics 159.1 (1997):
As of claim 6, the modified model teaches all limitations of claim 1, but it does not explicitly teach wherein the model parameters include geometries of the virtual vial and the virtual stopper.
While Corveleyn teaches wherein the model parameters include geometries of the virtual vial and the virtual stopper (Page 59, Two milliliters of a 10% w:v solution of maltodextrin DE 22 (Eridania-Beghin Say-Cer estar, Vilvoorde, Belgium), was placed into 8 ml Type I glass vials (Gaasch Packaging, Mollem, Belgium). Bromobutyl 20 mm stoppers FM257:2 SN0 and chlorobutyl 20 mm stoppers FM140:1 SAF1 (Helvoet Pharma) were dried at 100°C for 24 h and partially inserted into the vials).
Corveleyn is considered to be analogous to the claimed invention because it focus on moisture absorption and desorption of different rubber lyophilization closures. Therefore it would be obvious for a person of ordinary skill in the art, before the effective filling date to use Corveleyn teaches of using different stopper for vial with different parameters including size and temperature order to use a proper stopper on the modified model.
The motivation would have been in order to choice a proper stopper formulation parameter for moisture control of freeze-dried formulations by computing the water content of the stopper by analyzing the moisture absorption of different stopper lyophilization closure for different temperature and relative humidity ( Corveleyn, abstract , page 64).
Claim 19 is also in the same scope as that of claim 6, therefore claim 19, is rejected under the same rational as claim 6.
As of claim 7, the modified model teaches all the limitations of claim 1, but it does not explicitly teach wherein the model parameters include one or more of:a moisture diffusivity coefficient of the virtual stopper; a density of the virtual stopper; or a starting water amount or concentration of the virtual stopper.
While Corveleyn teaches wherein the model parameters include one or more of: a moisture diffusivity coefficient of the virtual stopper; a density of the virtual stopper; or a starting water amount or concentration of the virtual stopper.(page 62,
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) as shown on Fig. 3, before sterilization is considered as a starting water amount.
Corveleyn is considered to be analogous to the claimed invention because it focus on moisture absorption and desorption of different rubber lyophilization closures. Therefore it would be obvious for a person of ordinary skill in the art, before the effective filling date to use Corveleyn teaches of using a starting water amount for a stopper order to use a proper stopper on the modified model.
The motivation would have been in order to choice a proper stopper formulation parameter for moisture control of freeze-dried formulations by computing the water content of the stopper by analyzing the moisture absorption of different stopper lyophilization closure for different temperature and relative humidity ( Corveleyn, abstract , page 64).
Claim 20 is also in the same scope as that of claim 7, therefore claim 20, is rejected under the same rational as claim 7.
As of claim 13, the modified model teaches all the limitations of claim 1, but it does not explicitly teach , further comprising using the displayed information to select one or more of: a stopper type to use for the lyophilized drug product; a vial type to use for the lyophilized drug product; an ambient environment temperature to maintain for the lyophilized drug product; an ambient environment humidity to maintain for the lyophilized drug product; or a stopper drying target.
While Corveleyn teaches further comprising using the displayed information to select one or more of: a stopper type to use for the lyophilized drug product; a vial type to use for the lyophilized drug product; an ambient environment temperature to maintain for the lyophilized drug product; an ambient environment humidity to maintain for the lyophilized drug product; or a stopper drying target (page 62,
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) from figure 3 as shown above using the displayed information we can select the a stopper type to use for the lyophilized drug product.
Corveleyn is considered to be analogous to the claimed invention because it focus on moisture absorption and desorption of different rubber lyophilization closures. Therefore it would be obvious for a person of ordinary skill in the art, before the effective filling date to use Corveleyn teaches of using different stopper for vial with different parameters including size and temperature and select stopper type on the displayed information in order to use a proper stopper on the modified model for lyophilization.
The motivation would have been in order to choice a proper stopper formulation parameter for moisture control of freeze-dried formulations by computing the water content of the stopper by analyzing the moisture absorption of different stopper lyophilization closure for different temperature and relative humidity (Corveleyn, abstract , page 64).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
DE BEER THOMAS ( WO 2018033468 A1 Date Published 2018-02-22) this application is similar to the claimed invention since it focus on method and apparatus and container for freeze drying. It also computes temperature values of points located on the outer surface of the container wall using mathematical model.
Meyvis; Yves (US 20160090424 A1 Date Published 2016-03-31) this application is similar to the claimed invention since it teaches using of the Arrhenius equation to predict the shelf life of the lyophilized drug product at +5° C. and +25° C.
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/ABRHAM ALEHEGN TAMIRU/Examiner, Art Unit 2188
/RYAN F PITARO/Supervisory Patent Examiner, Art Unit 2188
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