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 Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the claimed particle to have “a ratio of a surface area to a volume is less than 0.6”. The specification states the following to define this ratio:
“Surface area/volume ratio = (sum of surface areas of each number average particle size Dn)/(sum of volumes of each number average particle size Dn).
The sum of surface areas of each number average particle size Dn is calculated using the following formula: Sum of surface areas of each number average particle size Dn = Sum of "surface area × existence ratio corresponding to each number average particle size Dn.
The sum of the volumes of each number average particle size Dn is calculated using the following formula: Sum of volumes of each number average particle size Dn = Sum of "volume × abundance ratio corresponding to each number average particle size Dn”.
The claims are implicitly drawn to a plurality of particles, in spite of a singular particle seemingly being recited because the article “a”, “an’ and “the” are intended to include plural forms. A population of particles has a single number average particle size and it is calculated as the sum of the diameters of each particle in the population divided by the number of particles in the population (see Moghadam et al. – previously cited - page 72 first column last partial paragraph and equation 2). Thus the meaning of the recitation “each number average particle size Dn” is unclear because the word ‘”each” suggests that there is more than one number average particle size for the particle population. Since the applicant is free to be their own lexicographer, the calculation required for a ratio of a surface area to a volume is not known because the definition seems to require multiple Dn values, but the population of particles only has one Dn value. The priority documents are not in English, thus it is not known if they provide clarifying language for this ratio. For the sake of compact prosecution and the application of prior art, a ratio of surface area to volume that is calculated as A / V will be used, where
A
=
∑
i
=
1
n
4
π
r
i
2
f
i
,
V
=
∑
i
=
1
n
4
3
π
r
i
3
f
i
, ri is the radius of a given particle in the population and fi is the numerical frequency of the given particle in the population.
Claim 5 recites “discharging the liquid droplet into a dry gas stream …wherein Td – Tm is 20 degrees Celsius or less, where Td represents a dew point temperature of the dry gas stream and Tm represents a wet bulb temperature of the liquid droplet”. The scope of this parameter based limitation remains unclear in regard to the scope of “dry gas”. Since this gas has a dew point and is later recited in claim 13 to have humidity, in spite of the word “dry”, it seems that the instant “dry gas” may contain water. It is unclear how much water is permitted or required in a gas stream to qualify as “dry gas” in claims 5-12.
Claim 6 recites “the solvent is removed from the liquid droplet under a condition that Ym – Y is 0.07 or more, where Ym represents a humidity when the solvent is saturated in the liquid droplet at a wet bulb temperature of the dry gas stream and Y presents a humidity of the dry gas stream”. Claim 5, from which claim 6 depends, recites a liquid droplet comprising an organic solvent. The recitation of claim 6 requires solvent removal under a condition when the humidity of the dry gas is less than the humidity this gas would have if the liquid droplet were saturated with solvent at the dry gas wet bulb temperature. This requirement appears to imply an additional source of water from the droplet or some other mechanism in the process in order for this difference to be non-zero. Thus it is unclear 1) which components are required of the droplet and the process in order to meet this criteria, 2) whether “humidity” refers to more than water in the dry gas, and 3) whether anhydrous particle composition liquids are embraced by the claim.
Claims 5 and 6 are additionally unclear because the process of drying a liquid droplet in a gas stream is dynamic and changes depending on the location where the dry gas dew point is assessed and its proximity to the entrance of the liquid droplet. Depending on the configuration of the drying apparatus, the droplet can be in contact with a dry gas stream whose properties are changing. For example, Papadakis et al. (previously cited) discuss the evolution over of the conditions inside a spray dryer as a function of time and internal location, where the spray dryer is a column provided with a concurrent stream of hot air and inlet fluid droplets (see abstract and page 2117 first column third full paragraph). The humidity and temperate of the air in the gas stream as well as their corresponding dew point changes, depending on the distance from the liquid feed nozzle in the radial and axial directions (see figures 6 and 7). Different dimensions of the chamber in which the solvent removal is conducted as well as the relative position of the discharged droplet and gas stream can also alter how these values change. The configuration of the solvent removal apparatus as well as the liquid feed temperature, liquid flow rate, inlet humidity, and inlet flow rate are all controllable parameters that result in various dew point temperatures at various locations in the apparatus. It is not clear which combinations of operating conditions correspond to and capture the claimed thermodynamic conditions such that it is clear when circumstances regarding the Td – Tm are invoked. A similar issue is present in claim 6 regarding its Ym – Y which also appears to be predicated on conditions that can be dynamic inside a drying apparatus or potentially invoked via some unclear set of operating conditions that are specific to the apparatus employed to perform the claimed drying method.
Claims not explicitly elaborated upon are also indefinite because they depend from an indefinite claim and do not add clarity.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 7 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. The claim recites that the physiologically active substance is water soluble; however, the parent claim already has this limitation. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3 and 11 are rejected under 35 U.S.C. 102(a)(1) as anticipated by Whitehead et al. (Journal of Biomedical Materials Research Part A 2018 106A:17-25).
Whitehead et al. disclose sustained release microparticles that encapsulate nerve growth factor (protein/polypeptide) in poly(lactide-co-glycolide) (PLGA) (fat soluble base material) (see abstract, page 16 first column first paragraph, and figure 6; instant claims 1 and 3). Various ratios of monomers in the polymer are detailed and produce different distributions of particle sizes (see page 16 first column first paragraph, page 19 second column second full paragraph, and figure 1). The particle distribution of the 75:25 monomer ratio yields a ratio of the surface area of the sustained release particles to the volume of the sustained release particles (area to volume) of about 0.24, a relative span factor of about 0.73, and a Dn of about 21.1 mm (as calculated by the examiner) [the values were calculated for the histogram in the figure by 1) employing the geometric mean for each particle size class, interpreting the x-axis numbers as the upper limits for each size class and the y-axis numbers as the numerical frequency percentage 2) surface area = sum of each class surface area x class frequency and 3) employing the histogram or linear interpolation to calculate the D10, D50, and D90, by number, for the relative span factor as instantly defined] (see instant claims 1-2 and 11). Therefore claims 1-3 and 11 are anticipated by or obvious over Whitehead et al.
Claim Rejections - 35 USC § 102/103
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
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 and 3 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Nie et al. (Journal of Applied Polymer Science 2017 134(44885):1-10)
Nie et al. disclose populations of poly(L-lactic acid) (PLLA) sustained release microparticles that comprise ibuprofen (see abstract and page 3; instant claims 1 and 3). Nie et al. detail size distribution assessments for different preparation conditions that produced different sized particles for blank particles that are loaded with ibuprofen post- production (see page 9 second column first-second full paragraphs, table 1 and figures 7-8). These are understood to correspond to the particles shown in figure 7 (in spite of what appears to be a typographical error listing 240K molecular weight as 24K) whose preparation solvents vary as tetrahydrofuran (THF) in a–c, 3:7 THF:dioxane in j–l, or dioxane in m–o. The particle distribution for the THF in 4a yields a ratio of surface area of the sustained release particles to the volume of the sustained release particles (area to volume) of about 0.1 (as calculated by the examiner) [the values were calculated for the histogram in the figure by 1) employing the geometric mean for each particle size class, interpreting the x-axis numbers as the upper limits for each size class and the y-axis numbers as the numerical frequency percentage and 2) surface area = sum of each class surface area x class frequency] (see instant claim 1). Alternatively, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ the exemplified THF produced particles to load the ibuprofen for sustained release because Nie et al. suggest to do so. Therefore claims 1 and 3 are anticipated by or obvious over Nie et al.
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 and 3-4 are rejected under 35 U.S.C. 103 as obvious over Nie et al. as evidenced by Le et al. (WO 97/42249).
Nie et al. disclose populations of poly(L-lactic acid) (PLLA) sustained release microparticles that comprise ibuprofen (see abstract and page 3; instant claims 1 and 3). Nie et al. detail size distribution assessments for different preparation conditions that produced different sized particles for blank particles that are loaded with ibuprofen post- production (see page 9 second column first-second full paragraphs, table 1 and figures 7-8). These are understood to correspond to the particles shown in figure 7 (in spite of what appears to be a typographical error listing 240K molecular weight as 24K) whose preparation solvents vary as tetrahydrofuran (THF) in a–c, 3:7 THF :dioxane in j–l, or dioxane in m–o. Nie et al. provide a number for each particle size class (see figure 7). The PLLA polymer is reported to have a 240 kDa molecular weight and an inherent viscosity of 1.6 dL/g (see page 2 first column first full paragraph and table 1). Le et al. teach PLLA with an inherent viscosity of 0.5 dL/g corresponds to a weight average molecular weight of 110,000 Da and implies that the PLLA of Nie et al. has a weight average molecular weight above 40,000 Da (see example II; instant claim 4). The particle distribution for the THF in 4a yields a ratio of surface area of the sustained release particles to the volume of the sustained release particles (area to volume) of about 0.1 (as calculated by the examiner) [the values were calculated for the histogram in the figure by 1) employing the geometric mean for each particle size class, interpreting the x-axis numbers as the upper limits for each size class and the y-axis numbers as the numerical frequency percentage and 2) surface area = sum of each class surface area x class frequency] (see instant claim 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that Nie et al. to employed THF with the named 240 kDa PLLA polymer produced particles to load the ibuprofen for sustained release because Nie et al. suggest that they did so. Therefore claims 1 and 3-4 are obvious over Nie et al. as evidenced by Le et al.
Claims 5, 7 and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Emaskaya et al. (Indian Journal of Pharmaceutical Sciences 2019 81(4):640-650) in view of Rothen-Wemhold et al. (European Journal of Pharmaceutical Sciences 1997 5:303-313), Beck-Broichsitter et al. (Journal of Controlled Release 2012 158:329-335), and Yazgan et al. (Scientific Reports 2017 7(1582):1-13).
Emaskaya et al. teach sustained release nanoparticles prepared by spray drying a liquid that contains a water soluble drug incorporated in poly(lactide-co-glycolide) (PLGA; fat soluble base material) (see abstract and page 640 first column first paragraph; instant claims 1 and 9). Here they detail employing a spray-drying apparatus called the Buchi B-90 (see page 641 first column last partial paragraph). The PLGA is known as Resomer® RG 504H which Rothen-Wemhold et al. detail has a weight average molecular weight of 60,000 Da (see table 1; instant claim 10). Emaskaya et al. teach producing a solution of PLGA in acetone (organic solvent) and dispersing their water soluble drug in an aqueous solution within the PLGA solution (see page 641 first column last partial paragraph). They note that the particles have a smooth surface (see page 647 second column first full paragraph).
Beck-Broichsitter et al. teach preparing sustained release nanoparticles via the Buchi B-90 Nano Spray Dryer (see abstract). They detail that this apparatus generates droplets via a vibrating mesh piezoelectric mesh that are ejected into a (dry) air stream (see page 330 first column last full paragraph instant claim 1). They go on to detail dissolving the PLGA in methylene chloride and an inlet (dry gas) temperature 30-50⁰C (see page 330 first column last-partial paragraph-second column first partial paragraph).
Yazgan et al. teach of the impact of drying conditions on a solution of fat soluble polymer discharged into a humid air environment (see abstract). Their model polymer is a polyester known for use in biomedical applications and likened to poly-L-lactide (PLLA) due to its utility, biodegradability, and biocompatibility (see page 1-page 2 third full paragraph). They employ polycaprolactone or PLLA in dichloromethane that is expelled as a strand into air at various humidity levels. They note that the proximity of the wet bulb temperature, Tm, of the dichloromethane and the dew point of the air, Tdp, controls the porosity and texture on the surface of the dried structure due to the condensation of water on the surface of the structure during solvent evaporation (see page 2 sixth-seventh full paragraphs and page 4 fourth full paragraph-page 5 third full paragraph). Minimizing the difference, Tdp-Tm, yields smooth, non-porous surfaces such that increases in their difference result in increases in texture and porosity and corresponds to increasing air humidity levels (see page figures 2 and 5). They illustrate that single digit differences, whether positive or negative, and others below 20⁰C correspond to non-porous or less porous surfaces from air humidity levels of 12% and 35% (see figure 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to practice the method of Emaskaya et al. where the Buchi B-90 spray dryer as taught by Beck-Broichsitter et al. is employed as the spray dryer because it appears to be the same as that employed by Emaskaya et al. It also would have been obvious to employ the dry air temperature and PLGA solvent of Beck-Broichsitter et al. as the simple substitution of one known element for another in order to yield a predictable outcome. Adjusting the humidity of this provided dry air to the range taught by Yazgan et al. would have been a matter of routine experimentation to optimize for the smooth surfaces Emaskaya et al. detail as desirable. Therefore claims 5, 7, and 9-10 are obvious over Emaskaya et al. in view of Rothen-Wemhold et al., Beck-Broichsitter et al., and Yazgan et al.
Claims 5, 7, 9-10, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Emaskaya et al. in view of Rothen-Wemhold et al., Beck-Broichsitter et al., and Yazgan et al. as applied to claims 5, 7, and 9-10 above, and further in view of Wan et al. (International Journal of Pharmaceutics 2016 498:82-95).
Emaskaya et al. in view of Rothen-Wemhold et al., Beck-Broichsitter et al., and Yazgan et al. render obvious the limitations of instant claims 5-7 and 9-10. While an instantly claimed inlet/dry gas temperature and humidity are rendered obvious and dichloromethane as a solvent for PLLA that is sprayed and dried into a desired structure is detailed, dichloromethane as a solvent for the PLGA is not explicitly detailed.
Wan et al. teach spray drying PLGA particles to generate drug releasing depots (see abstract). Here they detail solvents that are useful in this endeavor and name acetone as well as dichloromethane as suitable options and the superiority of dichloromethane over acetone as a solvent for PLGA (see page 89 fist column last partial paragraph-second column first partial paragraph and table 7; instant claim 13).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to exchange dichloromethane for the acetone in the method of Emaskaya et al. in view of Rothen-Wemhold et al., Beck-Broichsitter et al., and Yazgan et al. This modification would have been obvious as the simple substitution of one known element for another in order to yield a predictable outcome. Therefore claims 5, 7, 9-10, and 13 are obvious over Emaskaya et al. in view of Rothen-Wemhold et al., Beck-Broichsitter et al., Yazgan et al., and Wan et al.
Claims 5 and 7-10 are rejected under 35 U.S.C. 103 as being unpatentable over Oster et al. (Journal of Microencapsulation 2005 22(3):235–244) in view of Heng et al. (Expert Opinion on Drug Delivery 2011 8(7):965-972).
Oster et al. teach sustained release PLGA particles that encapsulate DNA that are made via spray drying (see abstract). Here they dissolve PLGA (fat soluble base material in methylene chloride (organic solvent) and disperse powdered DNA (water soluble physiologically active substance) in the solution (see page 238 first full paragraph; instant claims 5 and 8-9). The resulting suspension is spray dried by a Buchi B-190 spray dryer that discharges droplets of the suspension into an inlet gas temperature of 45-46⁰C (see page 238 first full paragraph). Oster et al. detail the PLGA to have a molecular weight of 41,000 (see page 237 first partial paragraph; instant claim 10). The resulting particles have a size of about 2.6 to 6.7 mm (see table 1). They note that the particles have a smooth surface (see page 240 first partial paragraph). Vibration is not detailed as the way in which the droplets are generated.
Heng et al. teach that the Buchi B-90 spray dryer is an improvement over the more conventional Buchi B-190 spray dryer and is ideally suited for generating particles sized 300 nm to 5 mm, a size of particular interest in the pharmaceutical field (see page 967 second column last partial paragraph-page 968 first column first partial paragraph). Unlike previous models, the B-90 droplets are generated via vibration mesh that yield precisely sized droplets and its collector permits recovery of dried particles at high yields (see page 968).
Yazgan et al. teach of the impact of drying conditions on a solution of fat soluble polymer discharged into a humid air environment (see abstract). Their model polymer is a polyester known for use in biomedical applications and likened to poly-L-lactide (PLLA) due to its utility, biodegradability, and biocompatibility (see page 1-page 2 third full paragraph). They employ polycaprolactone or PLLA in dichloromethane that is expelled as a strand into air at various humidity levels. They note that the proximity of the wet bulb temperature, Tm, of the dichloromethane and the dew point of the air, Tdp, controls the porosity and texture on the surface of the dried structure due to the condensation of water on the surface of the structure during solvent evaporation (see page 2 sixth-seventh full paragraphs and page 4 fourth full paragraph-page 5 third full paragraph). Minimizing the difference, Tdp-Tm, yields smooth, non-porous surfaces such that increases in their difference result in increases in texture and porosity and corresponds to increasing air humidity levels (see page figures 2 and 5). They illustrate that single digit differences, whether positive or negative, and others below 20⁰C correspond to non-porous or less porous surfaces from air humidity levels of 12% and 35% (see figure 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ the Buchi B-90 spray dryer as taught by Heng et al. instead of the Buchi B-190 spray dryer in the method of Oster et al. This modification would have been obvious as the application of the same technique to a similar process in order to yield the same improvement and as the simple substitution of one known element for another in order to yield a predictable outcome. Given a finite number of types of polymer molecular weights, interpreting the 41,000 molecular weight detail by Oster et al. as a weight average would have been obvious. Adjusting the humidity of the provided dry air to the range taught by Yazgan et al. would have been a matter of routine experimentation to optimize for the smooth surfaces Oster et al. detail as desirable. Therefore claims 5 and 7-10 are obvious over Oster et al. in view of Heng et al. and Yazgan et al.
Claims 5, 7-10, and 12 are rejected under 35 U.S.C. 103 as obvious over Oster et al. in view of Katoh et al. (US PGPub No. 2014/0038100), Ohtani et al. (US PGPub No. 2006/0210909) and Yazgan et al.
Oster et al. teach sustained release PLGA particles that encapsulate DNA that are made via spray drying (see abstract). Here they dissolve PLGA (fat soluble base material in methylene chloride (organic solvent) and disperse powdered DNA (water soluble physiologically active substance) in the solution (see page 238 first full paragraph; instant claims 5 and 8-9). The resulting suspension is spray dried in a process that discharges droplets of the suspension into an inlet gas temperature of 45-46⁰C (see page 238 first full paragraph). Oster et al. detail the PLGA to have a molecular weight of 41,000 (see page 237 first partial paragraph; instant claim 10). The resulting particles have a size of about 2.6 to 6.7 mm (see table 1). They note that the particles have a smooth surface (see page 240 first partial paragraph). Vibration is not detailed as the way in which the droplets are generated.
Katoh et al. teach of the usefulness of uniformly sized particles for drug delivery applications (see paragraph 3). They go on to teach an apparatus to generate such uniform particles, where a liquid droplet is ejected from a nozzle into a (dry) air stream that carries it to a solidifying device (see paragraph 7). The droplet includes raw material dissolved or dispersed in a solvent and the solvent in the droplet is evaporated in the air stream (see paragraph 110). They depict the solidifying device as a drying chamber in which the ejected droplets and the air stream meet which is the same general concept as spray drying (see figure 1). Katoh et al. go on to detail particle sizes of about 5 mm with a narrow polydispersity as attainable via the process (see table 1). In addition, Katoh et al. teach a Rayleigh fission ejector of Ohtani et al. as a specific example of a droplet generator that they envision (see paragraph 40; instant claim 12). Ohtani et al. teach their ejector to produce monodisperse droplets via vibration (see paragraph 13; instant claim 5).
Yazgan et al. teach of the impact of drying conditions on a solution of fat soluble polymer discharged into a humid air environment (see abstract). Their model polymer is a polyester known for use in biomedical applications and likened to poly-L-lactide (PLLA) due to its utility, biodegradability, and biocompatibility (see page 1-page 2 third full paragraph). They employ polycaprolactone or PLLA in dichloromethane that is expelled as a strand into air at various humidity levels. They note that the proximity of the wet bulb temperature, Tm, of the dichloromethane and the dew point of the air, Tdp, controls the porosity and texture on the surface of the dried structure due to the condensation of water on the surface of the structure during solvent evaporation (see page 2 sixth-seventh full paragraphs and page 4 fourth full paragraph-page 5 third full paragraph). Minimizing the difference, Tdp-Tm, yields smooth, non-porous surfaces such that increases in their difference result in increases in texture and porosity and corresponds to increasing air humidity levels (see page figures 2 and 5). They illustrate that single digit differences, whether positive or negative, and others below 20⁰C correspond to non-porous or less porous surfaces from air humidity levels of 12% and 35% (see figure 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ the particle forming apparatus of Katoh et al., where the droplet generator is that of Ohtani et al., as a spray dryer for the method of Oster et al. This modification would have been obvious as the application of the same technique to a similar process in order to yield the same improvement and as the simple substitution of one known element for another in order to yield a predictable outcome. Given a finite number of types of polymer molecular weights, interpreting the 41,000 molecular weight detail by Oster et al. as a weight average would have been obvious. Adjusting the humidity of the (dry) air stream to the range taught by Yazgan et al. would have been a matter of routine experimentation to optimize for the smooth surfaces Oster et al. detail as desirable. Therefore claims 5 and 7-10, and 12 are obvious over Oster et al. in view of Katoh et al., Ohtani et al. and Yazgan et al.
Response to Arguments
Applicant's arguments filed February 4, 2026 have been fully considered but they are not persuasive. In light of the amendment to the claims, the previous grounds of rejection under 35 USC 102 and 35 USC 103 are hereby withdrawn.
The applicant argues that the limitation concerning Td – Tm being 20 degrees Celsius or less is enabled. The issue of enablement was not raised in the rejection. Instead, the scope of the methods that are embraced by the recitation was stated to be unclear. The recitation includes a dewpoint which requires water be present in the gas, but the gas is recited as “dry”. Thus it is unclear if water is required in the gas such that “dry” does not carry its typical meaning. Additionally, it was noted that the humidity conditions within a spray dryer are dynamic and change depending on when and where a measurement is made. The air/gas stream in a spray dryer can run concurrently, counter-currently, as well as perpendicularly to the droplets ejected into the dryer chamber. Thus the recited condition of the gas stream contacting the droplet could occur in one region of the dryer at one instance while not occurring in another at the same instance. The applicant argues that the instant method is different from conventional spray drying but do not point to any particular active steps or apparatuses that delineate the two processes or make clear how the scope differs. The applicant states that Td is a value where the gas stream spurts out, but the claims do not state this limitation or anything similar to it. Therefore the scope of method steps, operating conditions, and apparatuses that are embraced by the recitation is not clear.
The applicant argues that they “discovered” that the difference in Td and Tm influences burst release. In light of Yazgan et al. correlating a shift from a smooth surface product to a porous surface product due to an increase in this difference and the known impact of porosity on release kinetics, it is not evident that the outcome recognized by the applicant was unexpected.
The applicant also argues that they were in possession of the surface area to volume ratio based on a number based particle diameter. This appears to be a response to a written description rejection that was not made. The rejection notes the applicant’s explicitly recited definition for the claimed surface area to volume ratio and the inability to use this algorithm to calculate the claimed ratio. While the applicant may have employed a different algorithm to calculate a surface area to volume ratio in an example, this does not change the explicit definition the applicant states for the claimed ratio of surface area to volume in their specification.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARALYNNE E HELM whose telephone number is (571)270-3506. The examiner can normally be reached Mon-Fri 9-5.
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/CARALYNNE E HELM/ Examiner, Art Unit 1615
/MELISSA S MERCIER/ Primary Examiner, Art Unit 1615
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