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 .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 07/24/2024 and 02/26/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
The claim objections are withdrawn following correction of capitalization and spelling out of SWFI.
WITHDRAWN REJECTIONS
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 2, 4, 8-9, 17, 19, and 21 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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.
Rejection of claim 4 is withdrawn following clarification of clinical reference range.
Rejection of claims 2, 9, 19 and 21 are withdrawn following cancellation of trademark terms.
Rejection of claim 8 is withdrawn following claim amendments.
Rejection of claim 17 is withdrawn following claim amendments
Claim Rejections - 35 USC § 103
Claims 1-4, 11-12, 14, 16, and 19-21 are rejected under 35 U.S.C. 103 as being unpatentable over 8,407,912 (Publication April 2, 2013; hereinafter "Hubbard;" See IDS 07/24/2024).
Rejection is withdrawn following claim amendments.
Claims 5 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over 8,407,912 (Publication April 2, 2013; hereinafter "Hubbard;" See IDS 07/24/2024) in view of Rogers et al (Transfusion. 2019 Apr; hereinafter "Rogers;" See PTO-892).
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over 8,407,912 (Publication April 2, 2013; hereinafter "Hubbard;" See IDS 07/24/2024) as evidenced by Hopkins (StatPearls Publishing; [Updated 2022 Sep 12; See PTO-892).
Claims 7-10 are rejected under 35 U.S.C. 103 as being unpatentable over 8,407,912 (Publication April 2, 2013; hereinafter "Hubbard;" See IDS 07/24/2024) in view of Liu et al (Transfusion. 2019 Feb; hereinafter "Liu;" See IDS 07/24/2024).
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over 8,407,912 (Publication April 2, 2013; hereinafter "Hubbard;" See IDS 07/24/2024) in view of Shakiba et a; (Advanced Powder Technology; hereinafter "Shakiba;" See PTO-892) Chen et al (Adv Drug Deliv Rev. 2021 May; hereinafter "Chen;" See PTO-892).
Rejection is withdrawn following claim amendments. New rejections are set forth below.
Double Patenting
Claims 1-4, 6-12, 16, 19-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 12,201,920 in view of 8,407,912 (Publication April 2, 2013; hereinafter "Hubbard;" See IDS 07/24/2024).
Claims 1-4, 6-12, 16-17, 19-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,975,274 in view of 8,407,912 (Publication April 2, 2013; hereinafter "Hubbard;" See IDS 07/24/2024).
Claims 11 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 12,405,057 in view of 8,407,912 (Publication April 2, 2013; hereinafter "Hubbard;" See IDS 07/24/2024).
The rejections are withdrawn following filing of Terminal disclaimers.
NEW REJECTIONS NECESSITATED BY CLAIM AMENDMENTS
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4, 6-9, 11-12, 14, 16, and 19-21 are rejected under 35 U.S.C. 103 as being unpatentable over 8,407,912 (Publication April 2, 2013; hereinafter "Hubbard;" See IDS 07/24/2024) in view of Liu et al (Transfusion. 2019 Feb; hereinafter "Liu;" See IDS 07/24/2024) further as evidenced by Cheng (PLoS One. 2013 Jun 7; hereinafter “Cheng;” See PTO-892).
Regarding claims 1, 3-4, 6 and 16: Hubbard disclosed a spray-dried plasma powder which can later be rapidly and easily reconstituted to produce transfusion grade plasma. The spray dried powder can be stored at least 2-3 years at virtually any temperature (e.g., −180° C. to 50° C.). (Hubbard col. 3, lines 10-15) Hubbard disclosed that the plasma powder may exhibit, a recovery rate for the protein between the plasma and the physiologically active reconstituted plasma, of at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, etc. (Hubbard col. 13, para 2, lines 5-15) This falls within the claimed within 25% recovery of plasma proteins compared to the levels before storage. It is also noted that −180° C to 50° C reads on the claimed −80° C to 45° C limit and at least 2-3 years reads on the claimed 1 day to 48 months limit. Accordingly, Hubbard reasonably suggested preservation of plasma protein levels following drying and storage and reconstitution.
Liu further taught spray-drying donor plasma following pre-treatment with glycine-hydrochloric acid and subsequently reconstituting the spray-dried plasma with water for injection. (See Liu Abstract). Liu reported that the reconstituted spray-dried plasma retains greater than 80% levels of all tested functional coagulation factors and related proteins, with the product exhibiting coagulation function comparable to fresh frozen plasma. (See Liu Table 1). Liu further reports clot formation and comparable global homostatic function following reconstitution. (See Table 4 and Table 2). Thus, Liu provides further evidence that spray-dried donor plasma can be processed and reconstituted while retaining clinically relevant plasma protein and coagulation function, as required by claim 4.
With respect to the pH, Liu expressly taught that spray-dried plasma pretreated with glycine hydrochloric acid and reconstituted with water for injection exhibited a pH of approximately 7.03±0.11. (See Liu, p. 710 col. 2) Liu further stated that the European Pharmacopeia specifies a plasma-product pH between 6.5-7.6. (See Liu p. 709, col. 2, 2nd para). Thus, Liu’s disclosed reconstituted spray-dried plasma falls within the claimed pH range of about 6.5-7.8 without requiring post-reconstitution pH adjustment.
Liu taught that pretreatment with glycine -hydrochloric acid mitigates spray drying induced alkalinization and improves preservation of plasma proteins, including vWF and other coagulation-related proteins. Liu therefore provided a reason for a person of ordinary skill in the art to employ the disclosed pretreatment in the spray-drying process of Hubbard to obtain a reconstituted plasma of Hubbard to obtain a reconstituted plasma having physiologically compatible pH and preserved protein and coagulation characteristics.
Accordingly, the combination of Hubbard and Liu taught or reasonably suggested a spray-dried plasma made from donor plasma that can be stored for extended periods, reconstituted with water for injection, retain plasma protein levels, exhibit physiologically compatible pH and retain clinically relevant coagulation functionality, including clot formation.
Applicants’ arguments regarding absence of an express disclosure in Hubbard of the claimed pH and clot-formation characteristics have been considered. However, Liu supplies these teachings and demonstrates that glycine-HCl pretreatment followed by spray-drying and water-only reconstitution can provide the claimed pH and preserve the claimed coagulation function.
A person of ordinary skill in the art would have had reason to apply Liu’s known plasma pre-treatment and spray-drying teachings to spray—dried plasma of Hubbard, with a reasonable expectation of transfusion grade reconstituted plasma having the disclosed characteristics.
It is noted that claim 16 is to a product by process. Product by process limitations are only given patentable weight to the extent that the process imparts a structural or functional distinction in the spray-dried plasma as compared to the prior art. Accordingly the process limitations do not distinguish the claimed product from the spray dried plasma disclosed in the prior art.
Regarding claim 2 and 19-21: The teachings of Hubbard’s disclosure of an average dried powder particle size of about 30 µm or less does not disclose the size of the particulates measured by a particle analyzer using the electrical sensing zone method of particulates having size between 2 µm to 60 µm or less is considered and acknowledged. It is submitted that particulate matter and microparticles in plasma and other biological products was well established in the art before the relevant date. Particle number and particle size were routinely analyzed in plasma products. For example Cheng taught characterization of particulate matter in plasma using a Beckmann Multisizer 4 coulter counter which “quantifies particles in suspension by measuring changes in electrical conductivity as particles pass through an aperture of 20 µm and allows accurate measurement of particles in the 0.4–10.0 µm size range”. Thus the technique to use a particle counter to determine particulate matter and size in plasma was known analytical technique.
Thus, a person of ordinary skill in the art evaluating the quality and transfusion-related suitability of reconstituted spray-dried plasma of Hubbard and Liu would have had reason to characterize the particulate population of the reconstituted product and compare it with the donor plasma. The selection of conventional particle-sizing technique, including electrical sensing sone analysis would have been a matter of routine matter of practice. Likewise, evaluating a predetermined size interval such as the 2-60 µm range would have been within the ordinary skill of the art when characterizing particulate matter in a biological product.
The claimed reduced mean particulate size represents a measurable property of the resulting reconstituted plasma rather than a structural limitation distinguishing the claimed composition of the spray-dried plasma. Applicants have not established that measuring particulate size in the reconstituted product or comparing the particulate size with the donor plasma required anything other than routine analytical testing. Neither has the Applicant provided evidence demonstrating that the claimed particulate size reduction is an unexpected result attributable to a patentably distinct feature of the claimed spray-dried plasma.
Accordingly, once the spray-dried plasma of Hubbard, as modified according to Liu, was prepared and reconstituted, determining the particulate-size distribution of the resulting product would have been a routine characterization of the product. To the extent the claimed reduced particulate-size characteristic is an inherent property of the resulting product, the discovery or identification of that inherent property does not impart patentability to an otherwise obvious product. Alternatively, to the extent the particulate-size characteristic is not inherent, routine optimization and characterization of the spray-drying and reconstitution process would have provided a reason to investigate and obtain the claimed particulate characteristics.
Regarding claim 7-9: The teachings of Hubbard are set forth above. It is noted that Hubbard did not teach or suggest the claimed ranges of C5a or vWF. Liu taught that single donor spray-dried plasma comprises 9.6 ± 3.7 nm/ml C5a which falls within the claimed range of claim 7. Further Liu taught that although spray drying cleaves HMW vWF multimers and often reduces vWF:RCo to less than 30% compared with the untreated starting plasma Regarding the presence of vWF” “ODP had FVIII levels comparable to other coagulation factors, albeit at the low end, indicating that the ability of vWF to stabilize FVIII was largely unaffected by the change of size distribution.” As such it can be gleaned that when reconstituted, there is an amount of von Willebrand factor that induces clot formation. Liu indicated that the amount of vWF was 50–200 IU/dL.
Regarding claim 11: Hubbard taught that the plasma powder described comprises ”less than 1% moisture by weight” (Hubbard, col. 12, lines 5-10).
Regarding claim 12: Hubbard indicated that “reconstituted plasma to a human patient utilizing the integrated storage and reconstitution device” (see cols. 1-3, in particular, col. 1, lines 56-61). As such Hubbard envisioned infusing their reconstituted plasma composition into a human subject.
Regarding claim 14: Hubbard taught spray-dried plasma that exhibits stability over extended periods and across a broad range of storage temperatures. It is well known in the art that biological materials, including plasma products \, are routinely stored under standard conditions such as room temperature (approximately 20-25 ºC) to preserve stability. For example, Hubbard taught “In an embodiment, spray dried plasma of the present invention can be stored at room temperature (e.g., between about 20° C. and 25° C.) for at least about 1 hour to about 12 months.” A person of ordinary skill in the art would have been motivated to store the spray-dried plasma at conventional temperature conditions as taught by Hubbard to maintain product stability and usability. The selection of specific storage temperatures and durations, including those recited in the claim represents a matter of routine optimization of result-effective variables. Therefore, the claimed subject matter would have been obvious.
Claims 5, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over 8,407,912 (Publication April 2, 2013; hereinafter "Hubbard;" See IDS 07/24/2024) in view of et al (Transfusion. 2019 Feb; hereinafter "Liu;" See IDS 07/24/2024) and Rogers et al (Transfusion. 2019 Apr; hereinafter "Rogers;" See PTO-892 of March 23, 2026), further as evidenced by Cheng (PLoS One. 2013 Jun 7; hereinafter “Cheng;” See PTO-892).
Regarding claim 5 and 22: The teachings of Hubbard in view of Liu are set forth above. As indicated above Hubbard taught plasma powder can be dried directly into the final, attached sterile container, which can later be rapidly and easily reconstituted to produce transfusion grade plasma. (Hubbard col. 2, line 9) It is noted that Hubbard did not explicitly teach that the spray dried plasma can be used for transfusion for up to about 26 hours. It is however noted that Hubbard taught a spray dried plasma which can be stored at least 2-3 years at virtually any temperature (e.g., −180° C. to 50° C). (see above). Hubbard noted that their spray-dried plasma when reconstituted, exhibits physiological activity substantially equivalent to Thawed Plasma, Liquid Plasma, FP24 (Plasma frozen within 24 hrs of phlebotomy), or FFP. (Hubbard col. 4, lines 40-45) As such it is recognized that spray dried plasma can be stored at room temperature for 24 hrs at 4º C. (See Rogers Table 2).
It would have been obvious for a person of ordinary skill in the art to apply the post-reconstitution handling conditions of Rogers to the spray-dried plasma of Hubbard. It is noted that both references are directed to spray-dried plasma products intended for transfusion. A person of ordinary skill in the art would have recognized that the storage conditions disclosed in Rogers represent a period during which the reconstituted plasma remains suitable for its intended use.
Further, regarding claim 22, Hubbard, as indicated above, disclosed that the plasma powder may exhibit, a recovery rate for the protein between the plasma and the physiologically active reconstituted plasma, of at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, etc. (Hubbard col. 13, lines 5-15) As such the disclosure of Hubbard supports that a level of one or more plasma proteins of the reconstituted spray dried plasma is within about 20%, as compared to a level of the one or more plasma proteins in reconstituted spray dried plasma contemporaneously after being spray dried.”
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over 8,407,912 (Publication April 2, 2013; hereinafter "Hubbard;" See IDS 07/24/2024) in view of Shakiba et a; (Advanced Powder Technology; hereinafter "Shakiba;" See PTO-892) Chen et al (Adv Drug Deliv Rev. 2021 May; hereinafter "Chen;" See PTO-892).
Regarding claim 17: The teachings of Hubbard are set forth above. It is noted that Hubbard did not teach or suggest low crystallization of cholesterol as required by instant claims, as compared to lyophilization. It is noted that a reduced number of cholesterol crystals, when viewed at 100X magnification, as compared to freeze dried plasma as recited in the instant claim is interpreted to mean lower number of cholesterol crystals in spray died formulation as compared to lyophilized formulation.
Spray drying is known to hinder crystallization. For example, Shakiba taught that “[t]he challenge of crystalline particle formation is the relatively long time scale nature of crystallization. In contrary, spray drying is a fast drying method in which most of the moisture is evaporated and the total residence time in the order of seconds, which conventionally hinders crystallization.” (Shakiba, p. 2300, col. 1, para 1). In contrast lyophilization is known to cause crystallization by decreasing solubility of the compositions of a formulation causing phase separation. For example, Chen taught that “Drying techniques such as lyophilization and spray-freeze drying involve freezing of solutions. Freezing involves a combination of different stresses destabilizing proteins, including cold denaturation, stress at interfaces, phase separation, and changes induced by concentrated components.“ (See Chen, p. 221, col. 1 -2) “Cooling rate dictates the number of ice nuclei and the size of the crystals, which is affected by the formulation composition. A faster cooling rate results in greater nuclei formation and smaller crystals. A fast-freezing step used for lactate dehydrogenase demonstrated larger extent of structural damage and lower activity recovery than for a slow-freezing rate. As smaller ice crystals have a larger surface area for proteins to be adsorbed, formulations with smaller ice crystals tends to lose their secondary and tertiary structures.
Differences in solubility of formulation composition causes phase separation in freezing, and certain components crystallize instead of maintaining in the amorphous matrix.” (Chen p. 221, col. 2, para 2).
As such, given the nature of the preparation of the dry powders, one of ordinary skill in the art would expect more cholesterol crystals in a lyophilized plasma versus a spray dried plasma. A person of ordinary skill in the art would have expected that different drying techniques give raise to different microstructures, with spray drying suppressing crystallization and freeze-drying promoting crystallization. A person of ordinary skill would have expected to arrive at a composition comprising reduced number of cholesterol crystals by spray drying as compared to freeze drying.
Conclusion
No claim is free of art.
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAGAMYA VIJAYARAGHAVAN whose telephone number is (703)756-5934. The examiner can normally be reached 9:00a-5:00p.
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/JAGAMYA NMN VIJAYARAGHAVAN/ Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633
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