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 of the species (SDSAS: hydrogen chloride) and (amino acid: glycine) in the reply filed on 12/01/2025 is acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-22 and 37-44 were examined on their merits.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at Pg. 18, Paragraph [0113]. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the Examiner on form PTO-892, they have not been considered.
Claim Objections
Claims 41 and 43 are objected to because of the following informalities: The word “having” should be changed to “has”. Appropriate correction is required.
Claim 42 is objected to because of the following informalities: The word “is” should be inserted between the words “proteins” and “vWf” and the word “the” inserted between the words “and” and “vWf”.
Claim 44 is objected to because of the following informalities: The word “the” should be inserted between the words “and” and “vWf”.
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.
Claim 14 is 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. The term “rapidly” 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. For purposes of examination, the Examiner has interpreted the limitation as being met by any combination of any volume of plasma and any volume of pretreatment solution over any period of time.
Claims 16-20 recite the limitation "C5a". There is insufficient antecedent basis for this limitation in the claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-41 and 43 are rejected under 35 U.S.C. § 103 as being unpatentable over Lui et al. (US 9,545,379 B2), in view of Hubbard, JR. et al. (US 2012/0167405 A1), both cited in the IDS.
Liu et al. teaches a method of producing spray dried plasma, comprising pretreating plasma from a blood donor (Column 5, Lines 35-36) with one or more SDSAS, wherein the SDSAS may be glycine-HCl at a concentration between about 0.001 and 0.050 mmol/mL (or about 1 to about 50 µmol/mL) of the plasma to create a formulated plasma;
and drying the formulated plasma with a spray dryer to create spray dried formulated plasma (Columns 24-25, Claim 1), and reading on Claims 1 and 37, steps a) and b), 39 and 40.
With regard to Claims 1 and 37, step b), Liu teaches the spray dryer head and spray drying chamber (e.g. the spray drying device) are formed from disposable materials (therefore meeting the limitation of being “disposable”) (Column 14, Lines 2-6).
With regard to Claims 1 and 37, steps c) and d), Liu teaches a spray drying head comprising a spray dry nozzle in fluid communication with the formulated plasma and a compressed/pressurized aerosol gas source wherein the pressurized aerosol gas atomizes the formulated plasma entering the drying chamber (Figs 4a-c);
a drying gas jet/inlet in communication with a drying gas source to provide drying gas to the drying chamber (Fig. 1a, #116 and 116a and Figs. 4a,b);
and a drying chamber wherein atomized plasma droplets dehydrate (e.g. remove water and produce humidity) in contact with drying gas to obtain spray dried formulated plasma (Figs. 4a,b)
With regard to Claim 1, step d), Liu teaches the reconstitution of the spray dried formulated plasma (Columns 24-25, Claim 1) and;
wherein the reconstituted the spray dried formulated plasma has a recovered amount of vWf (plasma protein) that is greater compared to reconstituted spray dried plasma not treated with SDSAS (Column 26, Claim 16).
With regard to Claim 10, Liu teaches the formulated plasma of Claim 1, step a) has a pH of about 5.5 to about 6.5 (contained within the claimed pH range of about 6 to about 6.6) (Column 25, Claim 10).
With regard to Claim 11, Liu teaches reconstituting the spray dried formulated plasma with sterile water (e.g. reconstitution solution) (Column 25, Claim 2).
With regard to Claim 12, Liu teaches the reconstituted plasma has a pH of about 6.8 to about 7.6 (contained within the claimed range of about 6.7 to about 7.8) (Column 25, Claim 3).
With regard to Claim 15, Liu teaches the formulated plasma is subjected to shear stress (e.g. agitation) prior to spray drying (see Fig. 4a, “feeding line”).
The teachings of Liu et al. were discussed above.
Liu et al. did not teach a method wherein the pretreatment solution comprises glycine in an amount ranging from about 50-110 µmol/mL of plasma or about 50 or 100 nM;
and HCl in an amount ranging from about 10-30 µmol/mL of plasma or about 1-50 nM, as required by Claims 1 and 37, step a) respectively;
wherein the spray drying nozzle comprises a vortex generator, as required by Claims 1 and 37, step c).
While the references listed above do not specifically teach the limitation of the amount ranges of glycine to HCl or molar ratio to glycine and HCl in the pretreatment solution of Claims 1 and 37, step a) and 2-8; or wherein the pretreatment solution has a pH between about 2-4, as required by Claim 9; one of ordinary skill in the art would recognize that the pH and concentration/molar ratio of glycine and HCl in a pretreatment composition comprising glycine-HCl are result-effective optimizable variables. Liu et al. teaches pretreating plasma with one or more SDSAS, wherein the SDSAS may be glycine-HCl at a concentration between about 0.001 and 0.050 mmol/mL (or about 1 to about 50 µmol/mL) of the plasma. These are endpoints in a total useful concentration range which overlaps the claimed range. The reference further teaches that SDSAS prevents or alleviates detrimental rising of pH during the spray drying process (Column 7, Lines 6-23) and that volatile strong acid (HCl) can be converted to fixed with amino acid (glycine) to render it non-volatile, making it easier to use (Column 8, Lines 4-8). This provides motivation for someone of ordinary skill in the art to practice or test the pretreatment solution pH, individual HCl and glycine concentration and molar ratio parameter values in a pretreatment solution widely to find those that are functional or optimal to sufficiently prevent or alleviate detrimental rising of pH during the spray drying process, which then would be inclusive or cover the instantly claimed values.
Absent any teaching of criticality by the Applicant concerning the pH and concentration of glycine and HCl in the pretreatment composition, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations as optimizable variables which can be met as a matter of routine optimization (see MPEP § 2144.05 (II)(B). Those of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make this modification in order to obtain a plasma pretreatment solution which prevents or alleviates detrimental rising of pH during a spray drying process. There would have been a reasonable expectation of success in making these modifications because the Liu reference is reasonably drawn to the same field of endeavor, that is, plasma pretreatment solutions comprising SDSAS and the spray drying thereof.
Hubbard, JR. et al. teaches a spray drying nozzle assembly comprising a vortex generator wherein cyclonic separation removes the atomized particles from the air/gas stream without the use of filters (Fig. 3a, #s 348 and 358 and 3b and Pgs. 8-9, Paragraph [0155]).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the spray drying head comprising a spray dry nozzle of Liu to include a vortex generator of Hubbard because this would allow in stream separation of the atomized formulated plasma droplets without the use of filters. Those of ordinary skill in the art would have been motivated to make this modification in order to isolate desired atomized formulated plasma droplets.
There would have been a reasonable expectation of success in making this modification because both references are drawn to the same field of endeavor, that is, spray dried plasma.
With regard to Claim 13, Liu teaches the reconstituted plasma is suitable for subjects to which it is to be administered (transfused) (Column 2, Lines 24-29). Therefore, the ordinary artisan would have recognized that the reference has “selected” a subject in need of plasma transfusion and it would have been obvious to perform such a transfusion. Those of ordinary skill in the art would have been motivated to make this modification in order to treat a subject in need of a plasma transfusion. There would have been a reasonable expectation of success in making this modification because Liu teaches that the reconstituted plasma is suitable for transfusion into subjects.
With regard to Claim 14, Liu teaches contacting plasma with the SDSAS pretreatment solution prior to spray drying (Column 4, Lines 26-35) and wherein the volume of the pre-spray dried plasma is determined and an SDSAS dose is measured to obtain the desired pH of the plasma formulation (Column 8, Lines 52-61). One of ordinary skill in the art would recognize that the volume of plasma and volume of pretreatment solution and the precent difference between them are result-effective optimizable variables.
Liu’s teaching of measuring the volume of plasma to be treated to determine how much SDSAS to mix with the plasma provides motivation for someone of ordinary skill in the art to practice or test the plasma and pretreatment solution volume and % difference parameter values widely to find those that are functional or optimal to produce the desired pH in the plasma formulation, which then would be inclusive or cover the instantly claimed values. Absent any teaching of criticality by the Applicant concerning the volume of plasma, pretreatment solution or the % difference thereof, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations as optimizable variables which can be met as a matter of routine optimization (see MPEP § 2144.05 (II)(B). Those of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make this modification in order to obtain a plasma formulation with the desired pH.
With regard to the limitations of Claims 16-20, 41 and 43, these would be inherent in the use of a pretreatment solution having an SDSAS (HCl) and amino acid (glycine) of Liu to pretreat a plasma sample because the instant Specification states at Pg. 3, Paragraph [0018] that:
It has been discovered that acceptable C5a levels result from a pretreatment solution having an SDSAS and an amino acid addition, and optionally rapid mixture/agitation of the pretreatment components. Acceptable C5a levels are those that are similar to C5a levels NFP or an FDA approved plasma product. In an embodiment C5a levels are reduced, as compared to C5a levels from rehydrated plasma that underwent pretreatment only with a SDSAS, and optional rapid mixture/agitation of the pretreatment components. In particular, levels of C5a for reconstituted plasma resulting from the pretreatment solution of the present invention can be between about 0.1 ng/mL to about 30 ng/mL and in particular between 8 ng/mL and 12 ng/mL (e.g., about 10 ng/mL). C5a levels are reduced,
as compared to plasma not subjected to a pretreatment solution having at least one SDSAS and at least one amino acid. In an embodiment, the C5a levels are reduced by about 20% or less (e.g., 20%, 15%, 10%, 5%, 1%), as compared to plasma not subjected to the pretreatment solution of the present invention. In another embodiment, C5a levels are about the same as that of never frozen plasma, or within about 20% or less (e.g., 20%, 15%, 10%, 5%, 1%) of C5a in never frozen plasma or approved FDA plasma products.
As the prior art teaches the same SDSAS/amino acid pretreatment solution to treat plasma as claimed, it would be expected to produce a plasma formulation with the same properties and characteristics, such as plasma proteins being about the same as in approved FDA plasma products (e.g., a corresponding clinical reference range). Further, the discovery of a previously unappreciated property of a prior art composition or the prior arts non-recognition of an inherent feature is not an indicial of non-obviousness. See the MPEP at 2112, I. and II.
With regard to Claims 21, 22, 37, step d) and 38; respectively that: the one or more plasma proteins is vWf and the amount thereof is about 5-40% or 10-35% greater than that of reconstituted plasma not pretreated with SDSAS;
and wherein an amount of plasma proteins in the reconstituted plasma is within 10% or 20% of that in plasma not subjected to step a), Liu teaches that the spray dried formulated plasma (same percentage whether reconstituted or not) has a recovery of active vWf at least 10-20% greater (overlapping the claimed ranges) than the recovery obtained from plasma not treated with SDSAS (Column 2, Lines 65-67 and Column 3, Lines 1-5).
Claim(s) 1-41, 42, 43 and 44 are rejected under 35 U.S.C. § 103 as being unpatentable over Lui et al. (US 9,545,379 B2), in view of Hubbard, JR. et al. (US 2012/0167405 A1), both cited in the IDS, as applied to Claims 1-41 and 43 above, and further in view of Ng et al. (2015).
The teachings of Liu et al. and Hubbard, JR. et al. were discussed above.
The Examiner notes that Liu discloses that vWf activity can be measured by the vWf:ristocetin cofactor assay and vWf amount can be measured by vWf antigen assay (Column 6, Lines 59-67).
Neither Liu or Hubbard teaches that the vWf antigen amount or vWf ristocetin cofactor amount is between about 50-200 IU/dL, as required by Claims 40 and 44.
Ng et al. teaches that the normal range for vWf antigen amount and vWf ristocetin cofactor amount is generally between about 50-200 IU/dL (Pg. 2030, Column 2, Lines 28-29 and Pg. 2031, Column 1, Lines 10-11).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of producing spray dried plasma of Liu so that the vWf antigen amount or vWf ristocetin cofactor amount in the reconstituted plasma is between about 50-200 IU/dL because this is the normal concentration range for these compounds.
Those of ordinary skill in the art would have been motivated to make this modification in order to produce and/or use a plasma product which is as close to normal in vivo plasm as possible. There would have been a reasonable expectation of success in making this modification because Liu produces a spray dried plasma product suitable for transfusion into a subject in need thereof and Ng teaches the normal concentrations of components found in plasma.
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 1-5, 9-12, 14-18, 21 and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 5, 6-9 and 10-12 of copending Application No. 18/467,074 in view of Lui et al. (US 9,545,379 B2).
Instant Claim 1 is drawn to a method of producing spray dried plasma from a plasma from one or more donors, the method comprising the steps of:
a) combining plasma with a pretreatment solution, wherein the pretreatment solution comprises
i) glycine in an amount ranging between-from about 50 µmole/mL of plasma and-to about 110 µmole/mL of plasma, and
ii) hydrochloric acid (HCI) in an amount ranging between-from about 10 µmole/mL of plasma to about 30 µmole/mL of plasma, to thereby obtain formulated plasma; and
b) drying the formulated plasma with a spray drying system that includes a spray drying disposable device to create spray dried formulated plasma, wherein the spray drying disposable device comprises:
c) a spray drying head comprising:
i) a spray dry nozzle assembly in fluid communication with the formulated plasma and a pressurized aerosol gas source that provides a pressurized aerosol gas, wherein spray drying nozzle comprises a vortex generator, wherein, when in use, the pressurized aerosol gas atomizes the formulated plasma entering the drying chamber to thereby obtain atomized plasma droplets;
ii) one or more drying gas jets in communication with a drying gas source that provides a drying gas, wherein, when in use, the one or more drying gas jets provide the drying gas to the drying chamber; and
d) a drying chamber, wherein, when in use, atomized plasma droplets evaporate when coming into contact with the drying gas emitted from the one or more drying gas jets to thereby obtain spray dried formulated plasma and humid air;
wherein when the spray dried formulated plasma is reconstituted, an amount of one or more plasma proteins recovered in the reconstituted plasma is increased, as compared to that in reconstituted plasma not subjected to step a).
This is made obvious by Claim 1 of the ‘074 application which is drawn to:
a method of producing spray dried plasma, the method comprising the steps of: a) combining plasma with a pretreatment solution, 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;
and b) drying the formulated plasma with a spray drying system and a spray drying disposable device having a spray drying head and a drying chamber, wherein the spray drying system having a drying gas source providing a drying gas that, when in use, communicates with the drying chamber, a plasma source providing a plasma and a pressurized aerosol gas source providing a pressurized aerosol gas, the spray drying disposable device comprising: i) the spray drying head comprising: (1) a spray dry nozzle assembly, wherein, when in use, is in fluid communication with the plasma source from the spray drying system and the pressurized aerosol gas source from the spray drying system, wherein, when in use, the pressurized aerosol gas flows in a vortex pattern and atomizes the plasma entering the drying chamber to obtain atomized plasma droplets; ii) the drying chamber, wherein, when in use, atomized plasma droplets evaporate 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 and the humid air is allowed to pass; to thereby create spray dried formulated plasma; wherein 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.
The teachings of the ‘074 application were discussed above.
The ‘074 application did not teach a disposable spray drying device or a method wherein the spray drying head comprises on or more drying gas jets in communication with a drying gas source that provides a drying gas, as required by instant Claim 1.
Liu et al. teaches a method of producing spray dried plasma, comprising pretreating plasma from a blood donor (Column 5, Lines 35-36) with one or more SDSAS, wherein the SDSAS may be glycine-HCl at a concentration between about 0.001 and 0.050 mmol/mL (or about 1 to about 50 µmol/mL) of the plasma to create a formulated plasma;
and drying the formulated plasma with a spray dryer to create spray dried formulated plasma (Columns 24-25, Claim 1).
With regard to Claims 1 and 37, step b), Liu teaches the spray dryer head and spray drying chamber (e.g. the spray drying device) are formed from disposable materials (therefore meeting the limitation of being “disposable”) (Column 14, Lines 2-6).
With regard to Claims 1 and 37, steps c) and d), Liu teaches a spray drying head comprising a spray dry nozzle in fluid communication with the formulated plasma and a compressed/pressurized aerosol gas source wherein the pressurized aerosol gas atomizes the formulated plasma entering the drying chamber (Figs 4a-c);
a drying gas jet/inlet in communication with a drying gas source to provide drying gas to the drying chamber (Fig. 1a, #116 and 116a and Figs. 4a,b);
and a drying chamber wherein atomized plasma droplets dehydrate (e.g. remove water and produce humidity) in contact with drying gas to obtain spray dried formulated plasma ( (Figs. 4a,b).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of the ‘074 application to use a disposable spray drying device comprising a drying gas jet/inlet in communication with a drying gas source to provide drying gas to the drying chamber because the ‘074 application does not indicate whether the device is disposable or how the drying gas is applied. Those of ordinary skill in the art would have been motivated to make this modification in order to provide a spray drying device which is not re-used and supplies jetted drying gas. There would have been a reasonable expectation of success in making this modification because both the ‘074 application and Liu are drawn to the same field of endeavor, that is, methods of making spray dried plasma.
Instant Claims 2&3, 4&5, 9, 10, 11, 12, 14, 15-18 and 21&22 are anticipated by Claims 1, 4, 5, 6, 7, 8, 9, 1, 11 and 12 of the ‘074 application.
This is a provisional nonstatutory double patenting rejection.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
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If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Sharmila G Landau can be reached at (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL C MARTIN/Examiner, Art Unit 1653 01/09/2026