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
Newly submitted claim 40 is directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: Claim 40 is drawn to a FVIII (anti-haemophilic factor or AHF) high-concentrate with a specific activity of at least 2.5 units AHF and a fibrinogen content of less than 0.25 mg/mg protein, wherein the concentrate comprises about 95%, 98%, 99% or at least about 99.5% pure FVIII. The newly submitted claim is an independent invention that recites exclusive characteristics such the amount of fibrinogen protein in the concentrate and the percent purity of the FVIII.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claim 40 is withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Status of Claims
Claims 1-38 were originally filed on 12/20/2021.
The amendment received on 04/08/2024, cancelled claims 36-38; amended claims 1-2, 8, 11-12, 21-22, 26-29, 32-35; and added new claim 39.
The amendment received on 04/23/2025, amended claims 1, 12-14 and 39; and added new claims 40-41.
The amendment received on 10/02/2025, amended claims 1, and 39-40.
The amendment received on 04/21/2026, amended claim 1, and cancelled claims 39-40.
Claims 1-35 and 41 are currently pending and under consideration.
Priority
The present application claims the benefit under 35 U.S.C 119 (e) to U.S. Provisional Application No. 63/111,191 filed November 9th, 2020. Applicants’ claim for the benefit of a prior-filed application under 35 U.S.C 119 (e) or under 35 U.S.C 120, 121, or 365 (c) is acknowledged.
Response to Arguments
1. Applicants’ arguments, see Response, filed 04/21/2026, with respect to the 35 U.S.C. 102(a)(1) rejection, have been fully considered and are persuasive. The 35 U.S.C. 102(a)(1) rejection to claims 1, 4-8, 16, 23-25 and 33-35 has been withdrawn.
2. Applicants’ arguments, see Response, filed 04/21/2026, with respect to the 35 U.S.C. 103 rejection, have been fully considered and are persuasive. The 35 U.S.C. 103 rejection to claims 1-3, 9-15, 17-22 and 26-32 has been withdrawn.
4. Applicants’ arguments, see Response, filed 04/21/2026, with respect to the 35 U.S.C. 103 rejection, have been fully considered and are persuasive. The 35 U.S.C. 103 rejection to claim 39 is moot.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
1. Claims 1-35 and 41are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Claim 1 was amended to recite “(a) reconstituting plasma cryoprecipitate to form reconstituted plasma cryoprecipitate”. Applicants stated in their remarks that “No new matter is added with this amendment and support for this amendment can be found throughout the application as-filed, for example, in [00101]-[00103] and [0045] (see Remarks, filed 04/21/2026, pg. 6 of 15). However, the support provided by Applicants does not support the amendment to claim 1, step a. Pursuant to MPEP 2111.01, under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the time of the invention. The Cambridge Dictionary defines the term “reconstitute” as to bring something back to its original state by adding liquid (see https://dictionary.cambridge.org/us/dictionary/english/reconstitute, retrieved on 09/25/2026). Therefore, the newly added limitation to claim 1 constitutes new matter because adding liquid to plasma cryoprecipitate does not return the plasma to ties original state as fresh plasma. Thus, the reconstituted plasma cryoprecipitate has not been adequately supported. Claims 2-35 and 41 are also rejected because they depend upon a rejected claim.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
3. Claims 1, 4, 33-35 and 41 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Burnouf et al., Vox Sang 1991; 60:8-15 (cited in the IDS filed on 11/26/2025) (here in after “Burnouf”).
For claims 1, 33 and 41, Burnouf discloses a purification process of FVIII (see pg. 8, Title and pg. 9, Fig. 1 purification scheme). Burnouf’s method comprises preparing a concentrate from plasma from whole blood donations by freezing the plasma at -60°C and storing at -35°C (see pg. 9, left column, second to last paragraph). Plasma bags were opened and the plasma was thawed at 0-2°C in a stirred heated vessel; the suspension was centrifuged to recover the cryoprecipitate (about 9 g/l plasma) which was then frozen at -60°C (see pg. 9, left column, second to last paragraph).
As evidenced by Sparrow; cryoprecipitate is a concentrate of high molecular weight plasma proteins that precipitate when frozen plasma is slowly thawed (see pg. 259, abstract). The concentrate contains factor VIII, von Willebrand factor (vWF), fibrinogen, factor XIII, fibronectin, and small amounts of other plasma proteins (see pg. 259, abstract). Therefore, Burnouf’s cryoprecipitate corresponds to plasma cryoprecipitate comprising the blood coagulation factor and fibrinogen as recited in instant claim 1. Burnouf’s purification scheme depicted in Fig. 1, shows that the highly purified FVIII as the final product of the process (see pg. 9, Fig. 1), thereby constituting wherein the blood coagulation factor is Factor VIII as recited in instant claims 33 and 41.
Burnouf also describes that the frozen cryoprecipitate was allowed to thaw, solubilized then mixed with Al(OH)3 (see pg. 9, left column, last paragraph). Thereby corresponding to (a) contacting the reconstituted plasma cryoprecipitate with solid Al(OH)3 as recited in instant claim 1, step (a). Burnouf adds that the cryoprecipitate was treated with Al(OH)3 and subjected to cold precipitation, since these steps were helpful in removing vitamin K-dependent clotting factors as well as some fibrinogen and fibronectin (see pg. 12, right column, second full paragraph). Thereby, constituting wherein fibrinogen is adsorbed onto the solid Al(OH)3 as recited in instant claim 1, step (a).
Burnouf describes that after 15 minutes of gentle stirring the solubilized cryoprecipitate with Al(OH)3, the mixture was centrifuged and the supernatant was treated with a mixture of 0.3% tri(n-butyl)phosphate (TnBP) and 1% Tween 80 for 8 h at 25°C (see pg. 9, right column, first paragraph). Thereby corresponding to (b) separating the fibrinogen adsorbed onto the solid Al(OH)3 from the blood factor, thereby forming the first fraction comprising the blood coagulation factor and the second fraction comprising the fibrinogen, as recited in instant claim 1.
For claim 4, Burnouf discloses that the cryoprecipitate was solubilized (see pg. 9, left column, last paragraph). As previously discussed in the 35 U.S.C 112(b) rejection above, the cryoprecipitate suspension and the reconstituted plasma cryoprecipitate are being interpreted as the exact same product. Thus, Burnouf’s solubilized cryoprecipitate constitutes forming a cryoprecipitate suspension prior to adsorbing the fibrinogen onto the solid Al(OH)3, as recited in instant claim 4.
For claim 34, Burnouf’s Fig. 1 shows depicts a step involving Al(OH)3 adsorption followed by cold precipitation (see pg. 9, Fig. 1), thereby constituting wherein centrifugation is not used in separating the fibrinogen adsorbed onto the solid Al(OH)3 from the blood coagulation factor, forming the first fraction and the second fraction, as recited in instant claim 34.
For claim 35, Burnouf describes that after 15 minutes of gentle stirring at room temperature, the mixture was cooled to 15°C and centrifuged in K 110 Jouan centrifuges at 5,000 g for 15 min (see pg. 9, right column, first paragraph). Thereby constituting wherein centrifugation is used in separating the fibrinogen adsorbed onto the solid Al(OH)3 from the blood coagulation factor, forming the first fraction and the second fraction, as recited in instant claim 35.
Accordingly, Burnouf’s disclosure anticipates the instantly claimed method of separating blood coagulation factor from fibrinogen in plasma cryoprecipitate as recited in instant claims 1, 4, 33-35 and 41.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness
(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
4. Claims 1 and 2-3 are rejected under 35 U.S.C. 103 as being unpatentable over Burnouf et al., Vox Sang 1991; 60:8-15 (cited in the IDS filed on 11/26/2025) (here in after “Burnouf”) as applied to claim 1 above, in further view of US 4,272,523 Date of patent Jun. 9, 1981 (cited in the IDS filed on 11/26/2025) (herein after “Kotitschke”) as applied to claims 2-3 herewith.
Regarding claim 1, please see Burnouf discussion above.
Regarding claims 2-3, Burnouf teaches mixing solubilized cryoprecipitate with Al(OH)3 and gently stirring at room temperature during 15 minutes, as part of the purification process of FVIII . However, Burnouf does not expressly teach wherein the solid SiO2 is fumed SiO2, nor wherein the fumed SiO2 is hydrophilic colloidal SiO2, as recited in claims 2 and 3 respectively.
However, Kotitschke’s invention pertains to fractionating citrate-stabilized plasma wherein the stabilized plasma is adsorbed on colloidal silica, forming a precipitate comprising fibrinogen and a supernatant (see sheet 1 of 6, Fig. 1). Kotitschke adds that that when using low concentrations of colloidal silica in the adsorption of citrate plasma at temperatures between about 1° and 37° C, fibrinogen is attached practically specifically to the colloidal silica (i.e., SiO2), while the coagulation factors II, VII, IX and X remain preserved in the "residual citrate plasma" freed from the colloidal silica (see column 2, lines 33-39). As such, the combined teachings of Burnouf and Kotitschke are suggestive of the claim limitations recited in instant claims 2-3.
Furthermore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Burnouf with the teachings of Kotitschke in order to arrive at the claimed method. One of ordinary skill in the art would have been motivated to do so because it was known that between about 1° and 37° C, fibrinogen attaches to SiO2 as taught by Kotitschke. One of ordinary skill in the art would have had a reasonable expectation of success in achieving the claimed method given that fibrinogen is adsorbed onto solid Al(OH)3 after 15 minutes of gently stirring solubilized cryoprecipitate with Al(OH)3 at room temperature as taught by Burnouf; and given that the supernatant in both Burnouf and Kotitschke’s methods comprises blood coagulation factors. Therefore, combining Burnouf and Kotitschke teachings constitutes some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention, pursuant to KSR.
In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the above claims would have been obvious to one of ordinary skill in the art within the meaning of 35 U.S.C 103. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references discussed above.
Conclusion
No claims are 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 CLAUDIA E ESPINOSA whose telephone number is (703)756-4550. The examiner can normally be reached Monday-Friday 9:30-5:30 EST.
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/CLAUDIA ESPINOSA/Patent Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
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