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
Applicant has amended claims 1, 8, 10-12, 14, and 16 and canceled claims 19 and 20. Claims 1-16 are pending.
The amendments to the claims have overcome the claim objections of record.
The amendments to the claims have overcome the 112(b) rejections of record.
The amendments to the claims have necessitated new rejections under 103. See 103 rejections below for details.
Response to Arguments
Applicant’s arguments, see Remarks, filed 9/4/2026, with respect to the claim objections have been fully considered and are persuasive.
Applicant has argued that the claim objections have been overcome the amendments to the claims. Accordingly, the claim objections have been withdrawn.
Applicant’s arguments, see Remarks, filed 9/4/2026, with respect to the 112(b) rejections have been fully considered and are persuasive.
Applicant has argued that the 112(b) have been overcome the amendments to the claims. Accordingly, the 112(b) rejections have been withdrawn.
Applicant’s arguments, see Remarks, filed 9/4/2026, with respect to the 103 rejections have been fully considered but they are not persuasive.
Applicant has argued that the claims require that the spray dried particles are captured in the spray drying chamber, whereas Hubbard allegedly does not capture spray dried particles in the spray drying chamber, but instead in a collection chamber separated from the drying chamber by a neck (see page 12 of Remarks). Examiner finds this argument unpersuasive.
The claimed capture of spray dried particles in the drying chamber is anticipated by, or in the alternative, obvious over Hubbard. To elaborate, Hubbard teaches a drying chamber 102’’ configured to evaporate atomized plasma droplets within the drying chamber 102’’ in the presence of drying gas emitted from the drying gas source to thereby obtain dried plasma particles and humid air, wherein the dried plasma particles are captured by capture filter 118, and the humid air is allowed to pass (Figures 3 and 4, paragraphs [0046]-[0059]).
The capture filter 118 resides in the collection sub assembly 104’’ (Figures 3 and 4, paragraphs [0046]-[0059]). Hubbard very clearly teaches that the drying chamber and the collection sub assembly may be a “single unit (e.g., manufactured as a single plastic piece)” (paragraph [0044]). Therefore, in at least one embodiment of Hubbard, the collection sub assembly 104’’ is part of the drying chamber 102’’, and at least in said embodiment, the capture filter 118 is positioned within the drying chamber 102’’ on account of being positioned within the collection sub assembly 104’’ which is part of the drying chamber. Accordingly, in an embodiment of Hubbard the dried plasma particles are captured by the capture filter 118 in the drying chamber 102’’.
In the alternative, by teaching that the that the drying chamber and the collection sub assembly may be a “single unit (e.g., manufactured as a single plastic piece)” (paragraph [0044]), Hubbard would suggest to one of ordinary skill in the art making the collection sub assembly 104’’ part of (i.e. unitary with) the drying chamber 102’’.
If it were not implicit in base Hubbard, it would have been obvious to one of ordinary skill in the art before the effective filing date to further modify Hubbard in view of Hubbard’s own suggestions by making the collection sub assembly 104’’ part of (i.e. unitary with) the drying chamber 102’’. In Hubbard modified as such, the capture filter 118 would be positioned within the drying chamber 102’’ on account of being positioned within the collection sub assembly 104’’ which is part of the drying chamber. Accordingly, in Hubbard modified as such, the dried plasma particles would be captured by the capture filter 118 in the drying chamber 102’’.
Applicant has argued that “Hubbard does not have the claimed vortex generator in the nozzle assembly,” (page 12 of Remarks). Examiner finds this argument unpersuasive.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., a “vortex generator”) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Nevertheless, Examiner respectfully maintains that Hubbard teaches, or at least suggests, a vortex generator comprised of ridges 426’’ and troughs 427’’. See 103 rejection of claim 1 below for a detailed discussion of Hubbard’s teachings.
Applicant’s arguments indicate that Applicant does not consider the ridges 426’’ and troughs 427’’ of Hubbard to be a vortex generator, a review of Applicant’s disclosure as originally filed shows evidence to the contrary. Specifically, paragraph [00378] of Applicant’s specification recites the following:
“The vortex generated includes 4 channels but can have between about 2 and 12 channels (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 channels). Other types of shaped channels can be used. Fig. 43I [presumably Fig. 43Ib, as said Figure is the only one which shows three designs labeled A, B, and C] shows the design molded into nozzle cap 76. Designs A and B both show more linear channels but Design A have no equivalent of a bulbous head and Design B shows a bell-shaped head. Design C is similar to the design shown in Fig. 43I but with a lobe instead of a bulbous shape at the end. The present invention includes nozzle caps having Designs A and B but found the Design C appears to be a more efficient vortex generator. The various designs demonstrate that any combination of channels, heads and shapes can be used to generate a vortex in the annulus. Other types of channels include conical shaped channels including convert or divergent cone shapes and the like,” (emphasis added).
The forgoing disclosure of paragraph [00378] makes it clear that a vortex generator having “Design A” is within the scope of what Applicant considers to be a vortex generator. As is explicitly described in the forgoing disclosure of paragraph [00378], a vortex generator of “Design A” does not comprise any bulbous head. Furthermore, as can be seen in Applicant’s Figure 43Ib (reproduced below), a vortex generator of “Design A” has straight channels.
Comparing “Design A” to the ridges 426’’ and troughs 427’’ as depicted in Figure 12 of Hubbard (also reproduced below), shows that said the ridges 426’’ and troughs 427’’ represent a vortex generator of “Design A”. It is noted that Hubbard’s vortex generator has six channels, whereas that of “design A” as depicted in Figure 43Ib has only 4. However, Applicant’s paragraph [00378] very clearly states that the vortex generator is not limited to designs with 4, and explicitly indicates that the vortex generator may include 6 channels. For at least this reason, the six channel design of Hubbard does not represent a substantial deviation from Applicant’s “Design A”. Regardless, the vortex generator of Hubbard (i.e. the ridges 426’’ and troughs 427’’) are at least sufficiently similar in structure to Applicant’s “Design A” as to provide clear indication that Hubbard’s vortex generator is within the scope of what Applicant considers to be a vortex generator.
Therefore, Examiner respectfully asserts that any interpretation of the claimed “vortex generator” as implicitly/necessarily: i) requiring the presence of a bulbous head and/or curved/arched channels, or ii) excluding the vortex generator of Hubbard, clearly does not represent “broadest reasonable interpretation consistent with the specification” (see MPEP 2111).
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In view of the above, Examiner maintains that Hubbard teaches a vortex generator (i.e. the ridges 426’’ and troughs 427’’) which is entirely consistent with Applicant’s usage of the term “vortex generator”.
Applicant has argued that the “relatively circular pattern” formed by Hubbard’s ridges 426’’ and troughs 427’’ does not amount to “the true vortex of the claimed invention” which allegedly “whirls and moves downward” (see page 12 of Remarks). Examiner respectfully disagrees.
”, none of Applicant’s claims as presently presented contain language requiring that a vortex as claimed includes or involves a flow of air which “whirls and moves downwards”. Furthermore, there is no explicit, limiting definition of “vortex” in Applicant’s claims which requires that said term be treated as referring to a flow of air which “whirls and moves downwards”. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Although Applicant points to paragraph [00378] of their specification to support their assertion the claimed vortex should be treated as involving a flow of air which “whirls and moves downwards”, after reviewing said paragraph of the specification as originally filed on 1/16/2023, Examiner has found no explicit, limiting definition of “vortex” therein, let alone one which limits “vortex” to flows of air which whirl and move downward. In fact, Examiner has been unable to find any instance of “whirl”, or any variation thereof (e.g. “whirls”), within any portion of Applicant’s specification as originally filed, or as amended on 1/17/2024.
Furthermore, Merriam-Webster defines “vortex” in the following ways:
1) “something that resembles a whirlpool”;
2a) “a mass of fluid (such as a liquid) with a whirling or circular motion that tends to form a cavity or vacuum in the center of the circle and to draw toward this cavity or vacuum bodies subject to its action” (emphasis added); and
2b) “a region within a body of fluid in which the fluid elements have an angular velocity”.
With the foregoing in mind, Examiner respectfully asserts that, under the broadest reasonable interpretation of “vortex” in the context of Applicant’s disclosure, there is no requirement that the claimed “vortex” involve a flow of air which whirls and moves downwards. Examiner further asserts that, the “relatively circular air flow about the nozzle 428''” disclosed by Hubbard (paragraph [0084]) is a “vortex” in at least sense 2a and sense 2b as defined by Meriam-Webster, i.e. the “relatively circular air flow about the nozzle 428''” is a vortex in that it is: i) a mass of fluid (air) with a circular motion, and ii) a region within a body of fluid (air) in which the fluid elements have an angular velocity (said angular velocity being present due to the circular flow of said air about the nozzle 428’’). Accordingly, “relatively circular air flow about the nozzle 428''” disclosed by Hubbard (paragraph [0084]) represents a “vortex” as claimed under the broadest reasonable interpretation of said term.
In addition, though it is of no consequence with respect to the claims as presently presented, Examiner respectfully disputes Applicant’s assertion that the “relatively circular air flow” in Hubbard DOES whirl and move downward.
Merriam-Webster defines the intransitive verb “whirl” as meaning “to move in a circle or similar curve especially with force or speed”. It is noted that when Applicant describes a vortex as involving a a flow of air that “whirls”, Applicant is using “whirls” as an intransitive verb, i.e. as opposed to a transitive verb or a noun. Accordingly, Examiner respectfully asserts that the “relatively circular air flow” in Hubbard “whirls” in the sense that it moves in a circle or similar curve.
Furthermore, though it is not explicitly taught, it is understood that said relatively circular air flow about the nozzle 428''” disclosed by Hubbard does move downward, i.e. at least when it passes through the annular 479’ opening between cannula 490’ and nozzle cap 470’ (Figures 11 and 12, paragraphs [0081]-[0084]).
Note: As stated in the 103 rejection of claim 1 set forth in the previous Office Action,
“Although paragraph [0084] and Figure 12 omit any explicit explanation as to exactly how the nozzle portion of Figure 12 fits into the nozzle portion of Figure 11, a careful analysis of Figure 12 reveals precisely how the nozzle portion of Figure 12 fits into the nozzle portion of Figure 11. Specifically, a comparison of Figures 11 and 12 reveals that the nozzle portion of Figure 12 is analogous to the inner nozzle 426’ of Figure 11, such that the vortex generator 426’’ and 427’’ forms the aerosol gas supply region (narrow region) 477’ of Figure 11 in cooperation with the nozzle cap 470’,” (page 11 of the 2/13/2024 Non-Final Rejection).
See pages 10-13 of the 2/13/2024 Non-Final Rejection for further details.
In view of the above, assuming for the sake of argument that the claims require a vortex involving a flow of gas which whirls and moves downward, the relatively circular flow of air disclosed by Hubbard would still satisfy the vortex as claimed.
Because, as discussed above, the relatively circular flow of air formed by the ridges 426’’ and troughs 427’’ in Hubbard constitutes a vortex in the claimed manner, said ridges 426’’ and troughs 427’’ satisfy the vortex generator as claimed.
Applicant goes on to argue many alleged distinctions between the vortex generator of Hubbard and their vortex generator as disclosed in the specification, e.g. that their vortex generator comprises a “bulbous head”, “curved/arched channels”, etc. (pages 12-16 of Remarks). Examiner finds this argument unpersuasive.
As pointed out above, the claims do not require a vortex generator, let alone a vortex generator having the specific features of the vortex generator as disclosed in Applciant’s specification. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Examiner notes that, even if Applicant were to amend the claims to recite a “vortex generator”, said vortex generator would be given the broadest reasonable interpretation, and would not be considered to include any feature that is not expressly claimed.
Applicant has argued that “Claims 1 and 16 have been amended to include that the molar ratio of amino acid to SDSAS is between about 1.5 and about 8.” Examiner respectfully disagrees.
While claim 1 has been amended to include this requirement, the amendments to claim 16 do not introduce any such requirement. Such a requirement remains absent from claim 16.
Applicant has argued that the combination of Hubbard and Liu (namely Liu) does not teach or fairly suggest a pretreatment solution having a molar ratio of amino acid to SDSAS between about 1.5 and about 8, as is allegedly required by claims 1 and 16 as amended (see pages 15-17 of Remarks).
This argument is moot with respect to claim 16 and its dependents, as said claims do not require the molar ratio.
This argument is persuasive with respect to claim 1 and its dependents. However, following further search and consideration, the amendments to claim have been found to necessitate new rejections under 103 over Hubbard in view of Meledeo et al. (“Spray-dried plasma deficient in high-molecular-weight multimers of von Willebrand factor retains hemostatic properties”; https://doi.org/10.1111/trf.15038). Meledeo et al. teaches use of a pretreatment solution having a molar ratio of amino acid to SDSAS that lies within the claimed range. See 103 rejection of claim 1 below for details.
Applicant has alleged that claim 1 is further distinguished from the combination of Hubbard and Liu by the newly added limitation requiring that the reconstituted plasma induces clot formation (see page 17 of Remarks). Examiner respectfully disagrees.
Liu provides clear indication that the reconstituted plasma in Hubbard modified in view of Liu as proposed in the previous rejections of claim 1 would necessarily induce clot formation (see Liu paragraphs [0006], [0010], [0040]-[0041], [0072], etc.)
Regardless, the reconstituted plasma of Hubbard modified in view of Meledeo as proposed in the 103 rejection of claim 1 set forth below would also induce clot formation as explained in the 103 rejection of claim 1 below.
Concerning the rejection of claim 11, Applicant argues the following:
With respect to Claim 11, the Examiner reasons that the recited C5a characteristic would be inherent because the method resulting from the proposed Hubbard/Liu combination is allegedly identical to the claimed method. Applicant respectfully disagrees. Inherency requires that the claimed characteristic necessarily results from the prior-art combination; it is insufficient that the characteristic merely may or could result.
(page 17 of Remarks).
The rejection of claim 11 was not made on the basis that the claimed C5a characteristic “may or could result” from the prior art combination. Rather, The rejection of claim 11 was, and continues to be, made on the basis that the claimed C5a characteristic would necessarily result from the prior art combination relied upon (Hubbard in view of Liu in the previous rejection, and Hubbard in view of Meledeo in the 103 rejections set forth below). Once an Examiner presents evidence or reasoning showing a particular property to be inherent, the burden of proof shifts to Applicant to establish the contrary (see MPEP 2112 V).
Applicant’s argument does not assert, much less prove, that the claimed C5a characteristic is not necessarily result from the prior art combination. Thus, said argument is insufficient to overcome the rejection of claim 11 on the basis of inherency.
Applicant has made arguments with respect to the Bakaltecheva secondary reference (see page 18 of Remarks). Said reference is not relied upon in any of the rejections below. Therefore, these arguments are moot.
Applicant has argued that the Ng evidentiary reference does not teach or suggest a pretreatment solution having the molar ratio of amino acid to SDSAS as required by claim 1. Ng is not relied upon to teach the claimed molar ratio feature. Therefore, this argument is moot.
Applicant’s arguments, see Remarks, filed 9/4/2026, with respect to the double patenting rejections have been fully considered and are persuasive.
Applicant has argued that the double patenting rejections have been overcome by the 9/4/2026 terminal disclaimer. Accordingly, the double patenting rejections have been withdrawn.
Claim Interpretations
The claims recite addition of a treatment solution comprising at least one amino acid and at least one Spray Dry Stable Acidic Substance (SDSAS) (claims 1 and 16). The claims elaborate that the SDSAS may be glycine HCl and that the amino acid may be Glycine.
Applicant’s specification states that “When an SDSAS is combined with an amino acid, an example includes glycine HCl. The SDSAS (e.g., (HCl, citric acid or lactic acid) and amino acid (e.g., glycine) can be added to the plasma in a combined form (e.g., glycine HCl) or as separate compounds (e.g., glycine and HCl),” (paragraph [0174] of the published specification). Based on this disclosure, it is fair to characterize an SDSAS comprising glycine HCl as constituting both an SDSAS and an amino acid contained within a pretreatment solution, the amino acid being specifically the glycine component of the glycine HCl.
Accordingly, any Glycine HCl can be fairly characterized as simultaneously constituting at least a portion of both the amino acid and SDSAS.
The following are new rejections necessitated by amendment.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-5, 8, and 10-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hubbard et al. (US 2012/0103536), hereafter referred to as Hubbard, in view of Meledeo et al. (“Spray-dried plasma deficient in high-molecular-weight multimers of von Willebrand factor retains hemostatic properties”; https://doi.org/10.1111/trf.15038), hereafter referred to as Meledeo.
With regard to claims 1-3 and 13: Hubbard teaches a method of producing spray dried plasma (abstract, Figures 3 and 4, paragraphs [0046]-[0059]), the method comprising:
Drying a plasma with a spray drying system and a spray drying disposable device having a spray drying head 140 and a drying chamber 102’’ to thereby created spray dried plasma, wherein the spray drying system having a drying gas source (dehumidifier and heater unit) 220 and 240 providing a drying gas that, when in use, communicates with the drying chamber 102’’, a plasma source (reservoir) 210 providing a plasma, and a pressurized aerosol gas source 202 providing a pressurized aerosol gas (Figures 3 and 4, paragraphs [0046]-[0059]). Note: Hubbard teaches that the spray drying device is a “spray drying disposable device”, i.e. a sterile disposable unit (paragraph [0048]).
The spray drying disposable device comprising:
i) The spay drying head 140, wherein the spray drying heat comprises spray dry nozzle assembly in fluid communication with the plasma source (reservoir) 210 and the pressurized aerosol gas source 202, wherein the spray dry nozzle assembly is configured such that the pressurized aerosol gas atomizes the plasma entering the drying chamber to obtain atomized plasma droplets (Figures 3 and 4, paragraphs [0040], [0046]-[0059]; emphasis on paragraphs [0040], [0046], [0050], and [0056]); and
ii) The drying chamber 102’’ configured to evaporate atomized plasma droplets within the drying chamber 102’’ in the presence of drying gas emitted from the drying gas source to thereby obtain dried plasma particles and humid air, wherein the dried plasma particles are captured by capture filter 118, and the humid air is allowed to pass (Figures 3 and 4, paragraphs [0046]-[0059]).
The capture filter 118 resides in the collection sub assembly 104’’ (Figures 3 and 4, paragraphs [0046]-[0059]). Hubbard very clearly teaches that the drying chamber and the collection sub assembly may be a “single unit (e.g., manufactured as a single plastic piece)” (paragraph [0044]). Therefore, in at least one embodiment of Hubbard, the collection sub assembly 104’’ is part of the drying chamber 102’’, and at least in said embodiment, the capture filter 118 is positioned within the drying chamber 102’’ on account of being positioned within the collection sub assembly 104’’ which is part of the drying chamber. Accordingly, in an embodiment of Hubbard the dried plasma particles are captured by the capture filter 118 in the drying chamber 102’’.
In the alternative, by teaching that the that the drying chamber and the collection sub assembly may be a “single unit (e.g., manufactured as a single plastic piece)” (paragraph [0044]), Hubbard would suggest to one of ordinary skill in the art making the collection sub assembly 104’’ part of (i.e. unitary with) the drying chamber 102’’.
If it were not implicit in base Hubbard, it would have been obvious to one of ordinary skill in the art before the effective filing date to further modify Hubbard in view of Hubbard’s own suggestions by making the collection sub assembly 104’’ part of (i.e. unitary with) the drying chamber 102’’. In Hubbard modified as such, the capture filter 118 would be positioned within the drying chamber 102’’ on account of being positioned within the collection sub assembly 104’’ which is part of the drying chamber. Accordingly, in Hubbard modified as such, the dried plasma particles would be captured by the capture filter 118 in the drying chamber 102’’.
In an embodiment of Hubbard, the spray dry nozzle assembly includes the nozzle portion of Figure 11. In other words, Hubbard implicitly discloses an embodiment wherein the spray dry nozzle assembly of the spray drying head 140 in the system of Figure 4 includes the nozzle portion taught in Figure 11 and paragraphs [0081]-[0084]).
In the alternative, Hubbard teaches that “A cross-sectional view of a nozzle portion of another embodiment of a spray drying head assembly is illustrated in FIG. 11,” (paragraph [0081]). By this teaching, Hubbard would at least suggest to one of ordinary skill in the art that the spray dry nozzle assembly of the spray drying head 140 in the system of Figure 4 could be configured to comprise the nozzle portion of Figure 11.
If it were not an implicit embodiment in base Hubbard, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify Hubbard in view of Hubbard’s own teachings by configuring the spray dry nozzle assembly of the spray drying head 140 in the system of Figure 4 to include the nozzle portion taught in Figure 11, in order to obtain a predictably functional spray drying device having a predictably functional spray drying head with a predictably spray drying nozzle assembly which are congruent with base Hubbard’s own teachings.
In the embodiment of Hubbard (or modified Hubbard) wherein the spray dry nozzle assembly of the spray drying head 140 in the system of Figure 4 includes the nozzle portion taught in Figure 11, the spray dry nozzle assembly comprises:
1) An aerosol gas supply region (narrow region) 477’ adapted to provide the pressurized aerosol gas to atomize plasma entering the drying chamber and obtain atomized plasma droplets (Figure 11, paragraphs [0081]-[0083]).
And 2) a cannula 490’ comprising a cannula opening (precision fluid channel orifice) 491’ in communication with the plasma, a wall within an inner surface and an outer surface, a top end, and a bottom end, wherein the bottom end has a bottom surface (Figure 11, paragraphs [0081]-[0083]).
In an embodiment of Hubbard, the spray dry nozzle portion of Figure 11 includes the nozzle portion as illustrated in Figure 12 (Figure 12, paragraph [0084]). In other words, Hubbard implicitly discloses an embodiment wherein the nozzle portion taught in Figure 11 includes the nozzle portion taught in Figure 12 and paragraphs [0084]. Thus, in the embodiment of Hubbard (or modified Hubbard) wherein the spray dry nozzle assembly of the spray drying head 140 in the system of Figure 4 includes the nozzle portion taught in Figure 11, said spray dry nozzle assembly further includes the nozzle portion taught in Figure 12.
The nozzle portion of Figure 12 includes a vortex generator made up of ridges 426’’ and troughs 427’’ which are arranged in a spiral orientation to induce a turbulence on passing aerosol gas, thus causing said aerosol gas to move in a vortex pattern (i.e. a relatively circular pattern) (Figure 12, paragraph [0084]).
Although paragraph [0084] and Figure 12 omit any explicit explanation as to exactly how the nozzle portion of Figure 12 fits into the nozzle portion of Figure 11, a careful analysis of Figure 12 reveals precisely how the nozzle portion of Figure 12 fits into the nozzle portion of Figure 11. Specifically, a comparison of Figures 11 and 12 reveals that the nozzle portion of Figure 12 is analogous to the inner nozzle 426’ of Figure 11, such that the vortex generator 426’’ and 427’’ forms the aerosol gas supply region (narrow region) 477’ of Figure 11 in cooperation with the nozzle cap 470’. For further detail as to how such a relationship is apparent from a comparison of Figures 11 and 12, see the annotated Figures 11 and 12 below which point to specific elements A, B, C, D, and E of the nozzle portion in Figure 11 as they appear in the nozzle portion of Figure 12.
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In view of the forgoing, it is understood that, in an embodiment of Hubbard (or modified Hubbard), the spray dry nozzle assembly of the spray drying head 140 in the system of Figure 4 includes a vortex generator 426’’ and 427’’ positioned in aerosol gas supply region (narrow region) 477’ and adapted to provide the pressurized aerosol gas in a vortex pattern and atomize the plasma entering the drying chamber to obtain atomized plasma droplets.
In the alternative, the above discussed teachings of Hubbard would at least suggest to one of ordinary skill in the art that the vortex generator 426’’ and 427’’ of Figure 12 be positioned in aerosol gas supply region (narrow region) 477’ of Figure 11.
If it were not an implicit embodiment in base Hubbard (or modified Hubbard), it would have been obvious to one of ordinary skill in the art before the effective filing date to modify Hubbard in view of Hubbard’s own teachings by configuring the spray dry nozzle assembly of the spray drying head 140 in the system of Figure 4 to include the nozzle portion taught in Figure 11, and by configuring the nozzle portion taught in Figure 11 to include in aerosol gas supply region (narrow region) 477’ the vortex generator 426’’ and 427’’ taught in Figure 12, in order to obtain a predictably functional spray drying device having a predictably functional spray drying head with a predictably spray drying nozzle assembly which are congruent with base Hubbard’s own teachings.
In view of the above, the spray dry nozzle assembly in Hubbard (or modified Hubbard) is configured such that the pressurized aerosol gas flows in a vortex pattern, i.e. on account of the vortex generator 426’’ and 427’’ disposed therein (Figure 11 and 12, paragraphs [0081]-[0084]).
Hubbard does not explicitly teach a step of combining plasma with a pretreatment solution prior to the step of drying, wherein the pretreatment solution comprises: i) one or more amino acids in an amount ranging between about 10 µmole/mL of plasma and about 110 µmole/mL of plasma, and ii) one or more Spray Dry Stable Acidic Substance (SDSAS) in an amount ranging between about 10 µmole/mL of plasma and about 30 µmole/mL of plasma, to thereby obtain formulated plasma, wherein the molar ratio of amino acid to SDSAS is between about 1.5 to about 8.
However, it is known in the art to pretreat plasma with such solutions prior to spray drying. Meledeo teaches combining a plasma with a pretreatment solution prior to spray drying said plasma, wherein the pre-treatment solution comprises glycine (an amino acid) in an amount of 50 µmole/mL (50 mM); and glycine-HCL (an SDSAS) in an amount of 20 µmole/mL (20 mM) (abstract subsection titled “STUDY DESIGN AND METHODS” [see page 714]; Materials and Methods subsection titled “Dried plasma formulations” [see page 715]). Based on the aforementioned molar concentrations, it is understood that said pretreatment solution comprises the amino acid (glycine) and the SDSAS in a molar ratio of 2.5. Note that the spray dried plasma treated with said pretreatment solution is referred to by the abbreviation (“SpDPGlyHCl:Gl”).
Meledeo’s results show that reconstituted spray dried plasma that had been treated with said pretreatment solution of glycine and glycine HCL has significantly increased levels of vWf compared to reconstituted spray dried plasma that has not been pretreated (Table 1; see columns titled SpDPuntreated and SpDPGlyHCl:Gl).
It would have been obvious to one of ordinary skill in the art before the effective filing date to further modify Hubbard in view of Meledeo by adding a step of combining plasma with a pretreatment solution prior to the step of drying, wherein the pretreatment solution comprises an amino acid, i.e. glycine, in an amount of 50 µmole/mL (50 mM) and an SDSAS, i.e. glycine-HCL, in an amount of 20 µmole/mL (20 mM), wherein the molar ratio of amino acid to SDSAS is 2.5, to thereby obtain formulated plasma, in order to obtain a spray dried plasma which, upon reformulation, has significantly increased levels of vWf compared to spray dried plasma that has not been pretreated.
The reconstituted plasma in modified Hubbard is necessarily capable of inducing clot formation when administered as evidenced by:
The fact that it is reconstituted plasma;
The fact that it has an amount of vWf, which is a protein which facilities platelet adhesion, as is well understood and acknowledged by Meledeo (for example in the final paragraph in left column on page 715);
Meledeo’s disclosures in Figure 2 and Results subsection titled “Coagulation function” which show that reconstituted spray dried plasma that has been pretreated with the pretreatment solution of glycine and glycine HCL is capable of inducing clot formation.
With regard to claim 4: The pretreatment solution comprises glycine in an amount of 70 µmole/mL, i.e. 50 µmole/mL (50 mM) of free glycine and 20 µmole/mL (20 mM) of glycine in the form of glycine HCL (Meledeo: abstract subsection titled “STUDY DESIGN AND METHODS” [see page 714]; Materials and Methods subsection titled “Dried plasma formulations” [see page 715]; see rejection of claim 1 above).
With regard to claim 5: The pretreatment solution comprises HCL (i.e. HCL in the glycine HCL) in an amount of 20 µmole/mL (20 mM) (Meledeo: abstract subsection titled “STUDY DESIGN AND METHODS” [see page 714]; Materials and Methods subsection titled “Dried plasma formulations” [see page 715]; see rejection of claim 1 above).
With regard to claim 8: The method of modified Hubbard further includes reconstituting the spray dried plasma with a reconstitution solution to produce reconstituted plasma (Hubbard: paragraphs [0005], [0040], [0045], [0107]-[0110]). Said reconstituted plasm will necessarily comprise plasma proteins on account of comprising spray dried plasma.
With regard to claim 10: Modified Hubbard does not explicitly teach that a first volume of said plasma is added to a second volume of the pretreatment solution to thereby obtain a formulated plasma, wherein the second volume is about 30% or less of the first volume.
However, a person having ordinary skill in the art would recognize that the volume of the pretreatment solution relative to the volume of the plasma is a result effective variable. Specifically, a person having ordinary skill in the art would recognize that if the volume of the pretreatment solution is too great, it will excessively dilute the plasma. Excessive dilution of the plasma would be recognized as disadvantageous on the basis that it would make it more difficult or impossible to successfully spray dry the plasma. "[When] the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation," (see MPEP 2144.05 II A).
It would have been obvious to one of ordinary skill in the art before the effective filing date to further modify Hubbard by:
1) optimizing the relative volumes of the pretreatment solution and the plasma, such that the volume of the pretreatment solution is no more than 30% of the volume of the plasma, in order to ensure that the plasma is not excessively diluted by the addition of the pretreatment solution; and
2) mixing the pretreatment solution and the plasma rapidly, i.e. soon after the plasma is obtained, in order to facilitate rapid spray drying before the plasma gets too old and becomes unusable.
With regard to claim 11: Because the method steps of modified Hubbard are identical to that of claim 11 (see rejection of claim 1 above), the results thereof will be the same. Accordingly, the amount of C5a is necessarily between about 4.7 to about 74 ng/mL and/or within 20% of that in reconstituted previously dried plasma that has been pretreated with SDSAS without an amino acid.
With regard to claim 12: The recovery of vWf attained by pretreatment with the solution of glycine and glycine HCL is about 34% greater (69.28% vs 35.61%) than would be attained from an otherwise identical spray dried plasma that has not undergone step a (Meledeo: Table 1; see columns titled SpDPuntreated and SpDPGlyHCl:Gl).
Claim(s) 6 and 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hubbard in view of Meledeo as applied to claims 1-3 above, and in further view of Liu et al. (US 2016/0082044), hereafter referred to as Liu.
With regard to claims 6 and 7: Modified Hubbard does not explicitly teach that the pH of the pretreatment solution is between about 2.0 and about 4.0, or that the formulated plasma of step a) has a pH of about 6.0 to about 6.6.
Liu teaches a method of spray drying plasma that has been pretreated with an SDSAS in a spray drying device comprising a spray drying head and a drying chamber (Figure 4a, abstract, paragraphs [0006]-[0007], [0011], and [0054]-[0056], claim 1, especially paragraph [0011] and claim 1).
Liu provides clear indication that the pH of the formulated plasma is a result effective variable. For example, Liu indicates that extreme pH during spray drying has negative effects on plasma proteins (paragraphs [0006] and [0007]), and that SDSAS is added to plasma for the express purpose adjusting the pH thereof (paragraphs [0009] and [0011]). "[When] the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation," (see MPEP 2144.05 II A).
Furthermore, Liu teaches “adjusting the pH of the CPD plasma or WB plasma with the SDSAS by bringing the amount of the acidic compound to about 0.001 to about 0.050 mmol/mL, which lowers the pH of the plasma to about 5.5 to about 6.5 or to about 7.2 to create formulated plasma,” (paragraph [0011]). This teaching indicates that a plasma pH of 5.5-7.2 is desirable, or at least workable, for the purposes of spray drying, and that such a plasma pH is achievable with the addition of an SDSAS in the claimed amount range.
It is noted that the claimed formulated plasma pH range is encompassed by the taught range. “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists,” (MPEP 2144.05 I).
Because the pH of the formulated plasma is understood to be a result effective variable, it is understood that the pH of the pretreatment solution added thereto is also a result effective variable for the same reasons, as the pH of the formulated plasma is intrinsically tied to the pH of the pretreatment solution added thereto.
It would have been obvious to one of ordinary skill in the art before the effective filing date to further modify Hubbard in view of Liu by optimizing the pH of the pretreatment solution so as to optimize the pH of the formulated plasma obtained therefrom, i.e. such that the pH pretreatment solution is between about 2.0 and about 4.0 and the pH of the formulated plasma is between about 6.0 and about 6.6, in order to obtain a method wherein the pH of the formulated plasma is suitable for spray drying.
Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hubbard in view of Meledeo as applied to claim 8 above, and in further view of Liu et al. (US 2016/0082044), hereafter referred to as Liu.
With regard to claim 9: Modified Hubbard does not explicitly teach that the reconstituted plasma has a pH of about 6.5 to about 7.8.
However, it would be clear that the pH of the reconstituted plasma is a result effective variable on the basis that, if it is to be administered to a patient with desirable effects, then it should be done so at a pH which is not too dissimilar from that of blood. Furthermore, Liu at least suggests that reconstituted spray dried plasma should have a pH of about 6.8-7.6 (paragraph [0013]). This teaching affirms the understanding that the pH of reconstituted plasma is a result effective variable, and that a pH of 6.8-7.6 is desirable or at least workable. "[When] the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation," (see MPEP 2144.05 II A).
It is noted that the claimed reconstituted plasma pH range overlaps with the taught range. “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists,” (MPEP 2144.05 I).
It would have been obvious to one of ordinary skill in the art before the effective filing date to further modify Hubbard in view of Liu by optimizing the pH of the reconstituted plasma, such that the reconstituted plasma has a pH of 6.5 to about 7.8, so as to yield a reconstituted plasma suitable for administering to a patient.
Claim(s) 14 and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hubbard in view of Meledeo as applied to claims 1-3 and 8 above, and further in view evidence from Ng (“Diagnostic approach to von Willebrand disease”; doi: 10.1182/blood-2014-08-528398).
With regard to claims 14 and 15: The vWf is measured by von Willebrand Factor Ristocetin Cofactor assay and has a value of about 69% (Meledeao: Table 1, Materials and methods subsection titled “vWf function” [see page 716], Results subsection titled “Excipient effects on SpDP performance” [see pages 717-718]). Said von Willebrand Factor Ristocetin Cofactor assay value of about 69% corresponds to a value of about 69 IU/dL, which is within the normal reference range as evidenced by Ng (see section titled “VWF:RCo”).
Claim(s) 16-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hubbard et al. (US 2012/0103536), hereafter referred to as Hubbard, in view of Liu et al. (US 2016/0082044), hereafter referred to as Liu.
With regard to claims 16-18: Hubbard teaches a method of producing spray dried plasma (abstract, Figures 3 and 4, paragraphs [0046]-[0059]), the method comprising:
Drying a plasma with a spray drying system and a spray drying disposable device having a spray drying head 140 and a drying chamber 102’’ to thereby created spray dried plasma, wherein the spray drying system having a drying gas source (dehumidifier and heater unit) 220 and 240 providing a drying gas that, when in use, communicates with the drying chamber 102’’, a plasma source (reservoir) 210 providing a plasma, and a pressurized aerosol gas source 202 providing a pressurized aerosol gas (Figures 3 and 4, paragraphs [0046]-[0059]). Note: Hubbard teaches that the spray drying device is a “spray drying disposable device”, i.e. a sterile disposable unit (paragraph [0048]).
The spray drying disposable device comprising:
i) The spay drying head 140, wherein the spray drying heat comprises spray dry nozzle assembly in fluid communication with the plasma source (reservoir) 210 and the pressurized aerosol gas source 202, wherein the spray dry nozzle assembly is configured such that the pressurized aerosol gas atomizes the plasma entering the drying chamber to obtain atomized plasma droplets (Figures 3 and 4, paragraphs [0040], [0046]-[0059]; emphasis on paragraphs [0040], [0046], [0050], and [0056]); and
ii) The drying chamber 102’’ configured to evaporate atomized plasma droplets within the drying chamber 102’’ in the presence of drying gas emitted from the drying gas source to thereby obtain dried plasma particles and humid air, wherein the dried plasma particles are captured by capture filter 118, and the humid air is allowed to pass (Figures 3 and 4, paragraphs [0046]-[0059]).
The capture filter 118 resides in the collection sub assembly 104’’ (Figures 3 and 4, paragraphs [0046]-[0059]). Hubbard very clearly teaches that the drying chamber and the collection sub assembly may be a “single unit (e.g., manufactured as a single plastic piece)” (paragraph [0044]). Therefore, in at least one embodiment of Hubbard, the collection sub assembly 104’’ is part of the drying chamber 102’’, and at least in said embodiment, the capture filter 118 is positioned within the drying chamber 102’’ on account of being positioned within the collection sub assembly 104’’ which is part of the drying chamber. Accordingly, in an embodiment of Hubbard the dried plasma particles are captured by the capture filter 118 in the drying chamber 102’’.
In the alternative, by teaching that the that the drying chamber and the collection sub assembly may be a “single unit (e.g., manufactured as a single plastic piece)” (paragraph [0044]), Hubbard would suggest to one of ordinary skill in the art making the collection sub assembly 104’’ part of (i.e. unitary with) the drying chamber 102’’.
If it were not implicit in base Hubbard, it would have been obvious to one of ordinary skill in the art before the effective filing date to further modify Hubbard in view of Hubbard’s own suggestions by making the collection sub assembly 104’’ part of (i.e. unitary with) the drying chamber 102’’. In Hubbard modified as such, the capture filter 118 would be positioned within the drying chamber 102’’ on account of being positioned within the collection sub assembly 104’’ which is part of the drying chamber. Accordingly, in Hubbard modified as such, the dried plasma particles would be captured by the capture filter 118 in the drying chamber 102’’.
In an embodiment of Hubbard, the spray dry nozzle assembly includes the nozzle portion of Figure 11. In other words, Hubbard implicitly discloses an embodiment wherein the spray dry nozzle assembly of the spray drying head 140 in the system of Figure 4 includes the nozzle portion taught in Figure 11 and paragraphs [0081]-[0084]).
In the alternative, Hubbard teaches that “A cross-sectional view of a nozzle portion of another embodiment of a spray drying head assembly is illustrated in FIG. 11,” (paragraph [0081]). By this teaching, Hubbard would at least suggest to one of ordinary skill in the art that the spray dry nozzle assembly of the spray drying head 140 in the system of Figure 4 could be configured to comprise the nozzle portion of Figure 11.
If it were not an implicit embodiment in base Hubbard, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify Hubbard in view of Hubbard’s own teachings by configuring the spray dry nozzle assembly of the spray drying head 140 in the system of Figure 4 to include the nozzle portion taught in Figure 11, in order to obtain a predictably functional spray drying device having a predictably functional spray drying head with a predictably spray drying nozzle assembly which are congruent with base Hubbard’s own teachings.
In the embodiment of Hubbard (or modified Hubbard) wherein the spray dry nozzle assembly of the spray drying head 140 in the system of Figure 4 includes the nozzle portion taught in Figure 11, the spray dry nozzle assembly comprises:
1) An aerosol gas supply region (narrow region) 477’ adapted to provide the pressurized aerosol gas to atomize plasma entering the drying chamber and obtain atomized plasma droplets (Figure 11, paragraphs [0081]-[0083]).
And 2) a cannula 490’ comprising a cannula opening (precision fluid channel orifice) 491’ in communication with the plasma, a wall within an inner surface and an outer surface, a top end, and a bottom end, wherein the bottom end has a bottom surface (Figure 11, paragraphs [0081]-[0083]).
In an embodiment of Hubbard, the spray dry nozzle portion of Figure 11 includes the nozzle portion as illustrated in Figure 12 (Figure 12, paragraph [0084]). In other words, Hubbard implicitly discloses an embodiment wherein the nozzle portion taught in Figure 11 includes the nozzle portion taught in Figure 12 and paragraphs [0084]. Thus, in the embodiment of Hubbard (or modified Hubbard) wherein the spray dry nozzle assembly of the spray drying head 140 in the system of Figure 4 includes the nozzle portion taught in Figure 11, said spray dry nozzle assembly further includes the nozzle portion taught in Figure 12.
The nozzle portion of Figure 12 includes a vortex generator made up of ridges 426’’ and troughs 427’’ which are arranged in a spiral orientation to induce a turbulence on passing aerosol gas, thus causing said aerosol gas to move in a vortex pattern (i.e. a relatively circular pattern) (Figure 12, paragraph [0084]).
Although paragraph [0084] and Figure 12 omit any explicit explanation as to exactly how the nozzle portion of Figure 12 fits into the nozzle portion of Figure 11, a careful analysis of Figure 12 reveals precisely how the nozzle portion of Figure 12 fits into the nozzle portion of Figure 11. Specifically, a comparison of Figures 11 and 12 reveals that the nozzle portion of Figure 12 is analogous to the inner nozzle 426’ of Figure 11, such that the vortex generator 426’’ and 427’’ forms the aerosol gas supply region (narrow region) 477’ of Figure 11 in cooperation with the nozzle cap 470’. For further detail as to how such a relationship is apparent from a comparison of Figures 11 and 12, see the annotated Figures 11 and 12 below which point to specific elements A, B, C, D, and E of the nozzle portion in Figure 11 as they appear in the nozzle portion of Figure 12.
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In view of the forgoing, it is understood that, in an embodiment of Hubbard (or modified Hubbard), the spray dry nozzle assembly of the spray drying head 140 in the system of Figure 4 includes a vortex generator 426’’ and 427’’ positioned in aerosol gas supply region (narrow region) 477’ and adapted to provide the pressurized aerosol gas in a vortex pattern and atomize the plasma entering the drying chamber to obtain atomized plasma droplets.
In the alternative, the above discussed teachings of Hubbard would at least suggest to one of ordinary skill in the art that the vortex generator 426’’ and 427’’ of Figure 12 be positioned in aerosol gas supply region (narrow region) 477’ of Figure 11.
If it were not an implicit embodiment in base Hubbard (or modified Hubbard), it would have been obvious to one of ordinary skill in the art before the effective filing date to modify Hubbard in view of Hubbard’s own teachings by configuring the spray dry nozzle assembly of the spray drying head 140 in the system of Figure 4 to include the nozzle portion taught in Figure 11, and by configuring the nozzle portion taught in Figure 11 to include in aerosol gas supply region (narrow region) 477’ the vortex generator 426’’ and 427’’ taught in Figure 12, in order to obtain a predictably functional spray drying device having a predictably functional spray drying head with a predictably spray drying nozzle assembly which are congruent with base Hubbard’s own teachings.
In view of the above, the spray dry nozzle assembly in Hubbard (or modified Hubbard) is configured such that the pressurized aerosol gas flows in a vortex pattern, i.e. on account of the vortex generator 426’’ and 427’’ disposed therein (Figure 11 and 12, paragraphs [0081]-[0084]).
Hubbard does not explicitly teach a step of combining plasma with a pretreatment solution prior to the step of drying, wherein the pretreatment solution comprises: i) one or more amino acids in an amount ranging between about 10 µmole/mL of plasma and about 110 µmole/mL of plasma, and ii) one or more Spray Dry Stable Acidic Substance (SDSAS) in an amount ranging between about 10 µmole/mL of plasma and about 30 µmole/mL of plasma, to thereby obtain formulated plasma.
However, it is known in the art to combine plasma with a pretreatment solution comprising at least an SDSAS to obtain a formulated plasma prior to spray drying. Specifically, Liu teaches a method of spray drying plasma in a spray drying device comprising a spray drying head and a drying chamber (Figure 4a, abstract, paragraphs [0006]-[0007], [0056]), wherein prior to spray drying, the plasma is combined with a pretreatment solution comprising an SDSAS in an amount ranging from 0.001-0.050 mmol/mL plasma(1-50 µmole/mL plasma) to obtain a formulated plasma (Figure 4a, abstract, paragraphs [0007], [0011], and [0054]-[0056], claim 1, especially paragraph [0011] and claim 1).
Liu teaches that glycine hydrogen chloride (glycine-HCl) is a suitable SDSAS (paragraphs [0009], [0045], [0051], [0167], [0169], and [0171], Figure 13, claim 4).
Liu teaches that by adding the pretreatment solution comprising SDSAS to the plasma and forming a formulated plasma prior to spray drying, several advantageous effects are achieved. For example, by creating a formulated plasma using the pretreatment solution (SDSAS): 1) higher recovery and better storage stability of active plasma proteins is achieved when compared to unformulated plasmas (paragraphs [0007]-[0010]); 2) spray dried plasma obtained from said formulated plasma can be rehydrated using water alone (paragraphs [0010] and [0046]); and most notably with respect to the claimed invention 3) spray dried plasma obtained from said formulated plasma has “a recovery of active von Willebrand factor (vWF) at least 10 to at least 20 percentage points greater than the recovery of active von Willebrand factor obtained from an otherwise identical spray dried plasma that has not undergone acid formulation with an SDSAS” (paragraph [0012]).
Liu teaches that “The invention further contemplates adjusting the pH of the CPD plasma or WB plasma with the SDSAS by bringing the amount of the acidic compound to about 0.001 to about 0.050 mmol/mL, which lowers the pH of the plasma to about 5.5 to about 6.5 or to about 7.2 to create formulated plasma” (paragraph [0011]), thereby providing clear indication that the amount of SDSAS relative to the amount of plasma is a result effective variable. "[When] the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation," (see MPEP 2144.05 II A).
Furthermore, it is noted that the claimed range of SDSAS amount 10-30 µmol/mL plasma lies entirely within the taught range of 0.001-0.050 mmol/mL plasma, i.e. 1-50 µmole/mL plasma. “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists,” (MPEP 2144.05 I).
It would have been obvious to one of ordinary skill in the art before the effective filing date to further modify Hubbard in view of Liu by adding a step of: combining plasma with a pretreatment solution prior to the step of drying, wherein the pretreatment solution comprises: a Spray Dry Stable Acidic Substance (SDSAS), said SDSAS being glycine hydrogen chloride (glycine HCl), to thereby obtain formulated plasma, in order to obtain a spray dried plasma which: i) has a higher recovery and better storage stability of active plasma proteins compared to unformulated plasmas, ii) ii can be rehydrated using water alone; and iii) has a recovery of active von Willebrand factor (vWF) at least 10 to at least 20 percentage points greater than unformulated plasmas.
In making said modification to Hubbard in view of Liu, it would have also been obvious to one of ordinary skill in the art to optimize the amount of the SDSAS, i.e. the glycine HCl, in the pretreatment solution, such that said SDSAS is added in an amount ranging between about 10 µmole/mL of plasma and about 30 µmole/mL of plasma, in order to obtain a predictably functional spray drying process wherein addition of the SDSAS has its indented effect.
It is understood that one mole of glycine HCl contains one mole of glycine. Accordingly, a solution comprising glycine HCl is understood to comprise glycine in the same molar amount. Thus, it is understood that the pretreatment solution of modified Hubbard, on account of comprising 10-30 µmole/mL plasma of glycine HCl, comprises an amino acid (i.e. the glycine in the glycine HCl) in an amount of 10-30 µmole/mL plasma.
It is noted that the SDSAS amount of 10-30 µmole/mL plasma corresponds to an amount of 10-30 mM (10-30 mmole/L).
On account of the addition of the SDSAS (glycine HCl) in modified Hubbard, it is understood that when the spray dried formulated plasma is reconstituted, an amount of functional von Willebrand factor (vWf) recovered in the reconstituted plasma is increased, as compared to plasma not subjected to step a (Liu: paragraphs [0012], [0045], [0169], and [0171], Figure 13).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any 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.
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/JONATHAN LUKE PILCHER/ Examiner, Art Unit 1772
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