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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-18, in the reply filed on 1/16/2026 is acknowledged.
Claims 19 and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1/16/2026.
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, Examiner interprets the claimed pretreatment solution as being satisfied by a solution comprising glycine HCl without any additional glycine, so long as the glycine HCl is present in an amount consistent with both the claimed SDSAS and amino acid amounts.
In the interest of abundant clarity, Examiner notes the claimed SDSAS amount lies within the claimed amino acid amount in all of claims 1, 2, and 4-18. It is understood that one mole of glycine HCl will comprise one mole of glycine and one mole of HCl. Accordingly, pretreatment solution having glycine HCl present in the claimed SDSAS amount will comprise amino acid (glycine) in an amount which satisfies the requirements of claims 1, 2, and 4-18.
On the other hand, claim 4 requires glycine in an amount (70-90 µmol/mL) which is greater than the specified upper limit for SDSAS amount (30 µmol/mL). Therefore, a pretreatment solution comprising glycine HCl would require the presence of additional Glycine to satisfy the requirements of claim 4.
Claim Objections
Claim(s) 1 and 16 is/are objected to because it contains/they contain informalities.
With regard to claim 1: In line 1, replace “the steps of” with --steps of--.
In line 10, replace “having a drying gas” with --has a drying gas--.
In line 14, replace “wherein, when in use” with --which when in use--.
With regard to claim 16: In line 1, replace “the steps of” with --steps of--.
In line 8, replace “having a drying gas” with --has a drying gas--.
In line 12, replace “wherein, when in use” with --which when in use--.
Appropriate correction is required.
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 1-18 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, in lines 13-18, the limitation "the spray drying head comprising [the elements of lines 14-18]". There is insufficient antecedent basis for this limitation in the claim.
To overcome this rejection, Applicant should amend line 13 of claim 1 to recite --i) the spray drying head, wherein the spray drying head comprises:--.
Claims 2-15 are rejected due to their dependency on indefinite claim 1.
Claim 10 recites “said plasma is rapidly added” in line 1.
The term “rapidly” in claim 10 is a relative term which renders the claim indefinite. The term “rapidly” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 11 recites the limitation "the amount of C5a" in line 1 and again in line 2. There is insufficient antecedent basis for this limitation in the claim.
Furthermore, it is unclear what comprises “the amount of C5a”. The wording of claim 11 suggests that it is a reconstituted plasma obtained from the spray dried formulated plasma obtained in claim.
Claim 14 recites the limitation "the one or more plasma proteins" in line 14. There is insufficient antecedent basis for this limitation in the claim.
Claim 16 recites, in lines 11-16, the limitation "the spray drying head comprising [the elements of lines 14-18]". There is insufficient antecedent basis for this limitation in the claim.
To overcome this rejection, Applicant should amend line 11 of claim 16 to recite --i) the spray drying head, wherein the spray drying head comprises:--.
Claims 17 and 18 are rejected due to their dependency on indefinite claim 16.
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) 1-3, 5-13, and 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 1-3, 13, 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, which when in use, is in fluid communication with the plasma source (reservoir) 210 and the pressurized aerosol gas source 202, wherein, when in use, 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’’, wherein, when in use, atomized plasma droplets evaporate 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, i.e. by capture filter 118, and the humid air is allowed to pass (Figures 3 and 4, paragraphs [0046]-[0059]).
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).
With regard to claim 5: Modified Hubbard does not explicitly teach that the pretreatment solution has HCl in an amount ranging between 15 and 25 µmole/mL plasma.
However, it is understood that one mole of glycine HCl contains one mole HCL. Accordingly, a solution comprising glycine HCl is understood to comprise HCl at the same 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 HCl (i.e. the HCl in the glycine HCl) in an amount of 10-30 µmole/mL plasma. Consequently, it is understood that if the amount of the SDSAS in the pretreatment solution of modified Hubbard were further optimized so as to be about 15-25 µmole/mL plasma, the HCl in said pretreatment solution would also be about 15-25 µmole/mL plasma.
As discussed in the rejection of claim 1 above, the amount of SDSAS is understood to be a result effective variable in view of Liu. Furthermore, an SDSAS amount of 15-25 µmole/mL plasma would still lie entirely within the range of acceptable amounts (0.001-0.050 mmol/mL plasma, i.e. 1-50 µmole/mL plasma) disclosed by Liu (see Liu: Paragraph [0011] and claim 1).
It would have also been obvious to one of ordinary skill in the art to further modify Hubbard in view of Liu by optimizing the amount of the SDSAS, i.e. the glycine HCl, in the pretreatment solution, such that said SDSAS and consequently the HCl therein, is added in an amount ranging between about 15 µmole/mL of plasma and about 25 µmole/mL of plasma, in order to obtain a predictably functional spray drying process wherein addition of the SDSAS has its indented effect.
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.
However, 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.
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]).
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.
With regard to claim 10: Modified Hubbard does not explicitly teach that a first volume of said plasma is rapidly 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 it is advantageous to combine the plasma and the treatment solution 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.
A person having ordinary skill in the art would further 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: Because the method steps of modified Hubbard are identical to that of claim 12 (see rejection of claim 1 above), the results thereof will be the same. Accordingly, the recovery of active vWf is necessarily about 5-40% greater than the recovery of active vWf obtained from an otherwise identical spray dried plasma that has not undergone step a.
Regardless, in the event that the recovery of active vWf is not necessarily about 5-40% greater than the recovery of active vWf obtained from an otherwise identical spray dried plasma that has not undergone step a, such an active vWf recovery is consistent with what Liu teaches as achievable through the addition of the SDSAS. Specifically, Liu teaches that addition of the SDSAS will result in the recovery of vWF may being “from about 10 to about 20 percentage points to about 40 percentage points greater than the recovery of active von Willebrand factor obtained from an otherwise identical spray dried plasma that has not undergone pretreatment with a SDSAS,” (paragraph [0012]). “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).
Furthermore, the teachings of Liu show that vWf recovery is a result effective variable, with higher recovery being desirable (Liu: paragraphs [0009] and [0012]). "[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).
If, for the sake of argument, the active von Willebrand factor recovery recited in claim 12 is not an inherent result of Liu’s method, then 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 carrying out the pretreatment step a so as to optimize the recovery of active vWf, i.e. such that the recovery of active vWf is necessarily about 5-40% greater than the recovery of active vWf obtained from an otherwise identical spray dried plasma that has not undergone step a, in order to obtain a spray dried plasma product capable of having a desirable and predictably achievable active vWf recovery upon reconstitution.
Claim(s) 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu in view of Hubbard as applied to claims 1 and 8 above, and further in view of Bakaltcheva et al. (“Freeze-dried whole plasma: Evaluating sucrose, trehalose, sorbitol, mannitol and glycine as stabilizers”; https://doi.org/10.1016/j.thromres.2006.07.005), hereafter referred to as Bakaltcheva.
With regard to claim 4: In modified Hubbard, the pretreatment solution comprises glycine, i.e. the glycine in the glycine HCl, in an amount of 10-30 µmole/mL plasma.
Modified Hubbard is silent to the pretreatment solution comprising glycine in an amount of about 70-90 µmole/mL plasma.
Bakaltcheva teaches adding 60mM (equal to 60 µmole/mL) glycine to plasma in order to stabilize said plasma prior to spray drying (abstract, sections titled “Effect of freeze-drying and consequent forced degradation at 40 °C on PT, APTT, TT and fibrinogen. Protection by different stabilizers” and “Effect of freeze-drying and consequent forced degradation at 40 °C on factors V, VII, VIII, IX and X. Protection by different stabilizers”). Bakaltcheva teaches that glycine added in said amount functions well as a protein stabilizer (see “discussion”, Figures 1-3, and sections titled “Effect of freeze-drying and consequent forced degradation at 40 °C on PT, APTT, TT and fibrinogen. Protection by different stabilizers” and “Effect of freeze-drying and consequent forced degradation at 40 °C on factors V, VII, VIII, IX and X. Protection by different stabilizers”).
Although Bakaltcheva studies glycine’s properties as a stabilizer in the specific context of freeze dried plasma, a person having ordinary skill in the art would reasonably expect that glycine would function well as a stabilizer in plasmas dried by other means, including spray drying.
Notably, if 60 µmole/mL plasma of free glycine were added to pretreatment solution in modified Hubbard, i.e. in addition to the glycine HCl, then the total amount of glycine in the pretreatment solution would be 70-90 µmole/mL plasma, which coincides exactly with the claimed range.
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 Bakaltcheva by adding 60 µmole/mL plasma of free glycine to the pretreatment solution, i.e. in addition to the glycine HCl, such that the total amount of glycine in the pretreatment solution would be 70-90 µmole/mL plasma, in order to impart the beneficial stabilizing effects of free glycine to the formulated plasma and subsequently the spray dried plasma.
Claim(s) 14 and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hubbard in view of Liu as applied to claims 1 and 8 above, and further in view of Ng (“Diagnostic approach to von Willebrand disease”; doi: 10.1182/blood-2014-08-528398).
With regard to claims 14 and 15: Because the method steps of modified Hubbard are identical to that of claims 14 and 15 (see rejection of claim 1 above), the results thereof will be the same. Accordingly, the von Willebrand Factor Antigen amount or von Willebrand Factor Ristocetin Cofactor amount is necessarily between about 50 IU/dL and about 200 IU/dL. Said amounts are levels within the corresponding clinical reference ranges (normal ranges) for von Willebrand Factor Antigen amount and von Willebrand Factor Ristocetin Cofactor amount, as evidenced by Ng (see sections titled “VWF:Ag” and “VWF:RCo” on pages 2030 and 2031).
Regardless, in the event that the von Willebrand Factor Antigen amount or von Willebrand Factor Ristocetin Cofactor amount is not necessarily between about 50 IU/dL and about 200 IU/dL, a person having ordinary skill in the art would recognize that such values for the von Willebrand Factor Antigen amount or von Willebrand Factor Ristocetin Cofactor are desirable.
As discussed above, Ng teaches that the clinical reference ranges (normal ranges) for von Willebrand Factor Antigen amount and von Willebrand Factor Ristocetin Cofactor amount are both 50-200 IU/dL (see sections titled “VWF:Ag” and “VWF:RCo” on pages 2030 and 2031). This teaching indicates that von Willebrand Factor Antigen amount and von Willebrand Factor Ristocetin Cofactor amount are result effective variables in the context of a spray dried reconstituted plasma, as it is understood that a vWf within the normal range would be desirable if the plasma is to be administered with desirable effects.
The teachings of Liu indicate that vWf recovery can be increased by adding the SDSAS. Accordingly, a person having ordinary skill in the art would recognize that it is possible to manipulate the von Willebrand Factor Antigen amount or von Willebrand Factor Ristocetin Cofactor amount in a spray dried plasma upon reconstitution, e.g. through addition of a treatment solution prior to spray drying. "[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).
If, for the sake of argument, the von Willebrand Factor Antigen amount or von Willebrand Factor Ristocetin Cofactor amount is not necessarily between about 50 IU/dL and about 200 IU/dL, then 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 carrying out the pretreatment step a and the spray drying step b so as to obtain a spray dried plasma having a von Willebrand Factor Antigen amount or von Willebrand Factor Ristocetin Cofactor amount between about 50 IU/dL and about 200 IU/dL upon reconstitution, in order to obtain a spray dried plasma which upon reconstitution comprises vWf within the normal reference range.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 and 37-44 of copending Application No. 17/945,126 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘126 application anticipate or otherwise render obvious the claims of the present Application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Bakaltcheva et al. (US 7,931,919) and Bakaltcheva (US 8,349,367) are patent documents covering subject matter that is at least similar to the Bakaltcheva NPL reference relied upon in the 103 rejections above.
Conclusion
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/JONATHAN LUKE PILCHER/Examiner, Art Unit 1772