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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/10/2025 has been entered.
Claim Status
The amendment of 06/10/2025 has been entered. Claims 1-31 are pending (claim set as filed on 06/10/2025). Claims 1-31 are currently under examination and were examined on their merits.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 08/14/2025 was considered in part. This IDS fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. Specifically, the provided reference document No. 3 (“Octapharma USA Announces FDA Approval of NUWIQ New Product Strengths, Expanding Hemophilia A Patient Treatment Options," New Jersey Business Magazine, August 22, 2017, 5 pages total) is not fully legible; this document has not been considered.
In order to have the struck-through references in the IDS considered by the Examiner, Applicant is asked to submit a new IDS having listed therein only the struck-through documents from this IDS. The IDS should be accompanied by a copy of each struck-through reference.
Claim Objections
Claims 13 is objected to because of the following informalities:
Claim 13 recites “764 to 1242 SEQ ID NO: 4” which should read “764 to 1242 of SEQ ID NO: 4”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 (b)
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 17-18, 22-25 and 29-31 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.
Claims 17-18, recite the term “preferentially”, which renders the claim indefinite since is unclear whether the limitations following the term are part of the claimed invention. See MPEP § 2173.05(d).
Claim 22 recites “the polypeptide comprising a truncated FVIII” which is indefinite for lacking antecedent basis because “polypeptide comprising a truncated FVIII” is not previously recited within the claim.
Claim 23 recites “the polypeptide” which is indefinite for lacking antecedent basis because “polypeptide” is not previously recited within the claim.
Claims 29-31 recite the phrase “molar ration”, which renders the term indefinite because it is unclear what “molar ration” means.
One of ordinary skill in the art would not be able to determine the metes and bounds of claims 17-18, 22-23 and 29-31, and thus, could not clearly determine how to avoid infringement of the claims.
In the interest of compact prosecution, claims 22 and 23 are interpreted to the broadest embodiment claimed. The Examiner notes that dependent claims 24-25 are included in the rejection since they fail to remedy the lack of antecedent basis in base claim 23.
Claim Rejections - 35 USC § 102
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 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.
Claims 22 and 29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schulte et al. (US 2018/0161402 A1, published on 06/14/2018), hereinafter ‘Schulte’.
Schulte’s general disclosure relates to relates to a polypeptide comprising a truncated von Willebrand Factor (VWF) for use in the treatment of a blood coagulation disorder, wherein the polypeptide carries a half-life extending moiety and is administered in molar excess over Factor VIII and/or endogenous VWF (see entire document, including abstract).
Regarding claim 22, pertaining to a method of making a composition, Schulte teaches a method for making a composition comprising coagulation factor VIII (FVIII), said method comprising mixing a polypeptide comprising a truncated von Willebrand Factor (VWF) and the FVIII to form a composition comprising the FVIII and the polypeptide comprising a truncated VWF (paragraphs [0241], [0014]; see claim 30), wherein the molar ratio of the polypeptide to the polypeptide comprising a truncated FVIII in the composition is greater than 20 (see claim 30).
Regarding the in vitro stability of coagulation factor VIII, it is noted that since Schulte teaches the instant method and composition recited in claim 22, Schulte’s coagulation factor VIII is expected to have the same properties, i.e. increased in vitro stability.
Regarding claim 29, pertaining to the molar ratio, Schulte teaches wherein said molar ratio is at least 200 (paragraphs [0014] and [0018]).
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.
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 factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
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 1-6, 17-18, and 12-21 are rejected under 35 U.S.C. 103 as being unpatentable over Schulte et al. (US 2018/0161402 A1, published on 06/14/2018), hereinafter ‘Schulte’.
Schulte’s general disclosure relates to relates to a polypeptide comprising a truncated von Willebrand Factor (VWF) for use in the treatment of a blood coagulation disorder, wherein the polypeptide carries a half-life extending moiety and is administered in molar excess over Factor VIII and/or endogenous VWF (see entire document, including abstract).
Regarding claims 1 and 17, pertaining to a method for increasing the in vitro stability of coagulation factor VIII (FVIII) in a composition, Schulte teaches mixing a polypeptide comprising a truncated von Willebrand Factor (VWF) and said FVIII to form a composition comprising the FVIII and the polypeptide comprising said truncated VWF (paragraphs [0241], [0014], [0082]; see claim 30), wherein the molar ratio of the polypeptide to the FVIII in the composition is greater than 20 (paragraph [0016], see claim 30).
Additionally, Schulte teaches storage of therapeutic formulations of a truncated von Willebrand Factor (VWF) (paragraphs [0014] and [0246]), and wherein VWR fragments increase the in vitro stability of FVIII (paragraph [0012]). It is noted that VWR fragment reads on truncated VWR (paragraph [0127]).
Regrading claims 2, Schulte teaches wherein VWR fragments increase the in vitro stability of FVIII (paragraph [0012]). It is noted that increased in vitro stability indicates increased storage stability.
Regarding claim 3, Schulte teaches wherein the molar ratio of the polypeptide to the FVIII in the composition is greater than 50 (see claim 30).
Regarding claim 4, Schulte teaches wherein the composition comprises a truncated VWF (see claim 30), which is produced by genetic engineering or fragmenting and therefore, truncated VWF is not a wild-type VWR.
Regarding claim 5, Schulte teaches wherein FVIII is recombinantly produced FVIII or plasma derived plasma derived FVIII (paragraph [0234]).
Regarding claim 6, Schulte teaches wherein said method comprises adding
a more than 20-fold molar excess to less than 10,000 fold excess of said polypeptide to said
FVIII (paragraphs [0014] and [0116]).
Regarding claim 12, Schulte teaches wherein said polypeptide binds to said FVIII with a dissociation constant KD of less than 1 nM (paragraph [0037]).
Regarding claim 13, Schulte teaches wherein the truncated VWF comprises amino acids 764-1242 of the instant SEQ ID NO: 4 (paragraph [0131]). It is noted that amino acids 764-1242 of Schulte’s SEQ ID NO: 4 are identical with amino acids 764-1242 of Applicant’s SEQ ID NO:4 (see alignment below; note, amino acids 764-1242 of Applicant’s SEQ ID NO:4 correspond to Qy 1-479).
GenCore version 6.5.2
Copyright (c) 1993 - 2025 Biocceleration Ltd.
OM protein - protein search, using sw model
Run on: December 12, 2025, 15:11:54 ; Search time 36 Seconds
(without alignments)
25597.724 Million cell updates/sec
Title: US-17-623-398-4_COPY_764_1242
Perfect score: 2709
Sequence: 1 SLSCRPPMVKLVCPADNLRA..........QICHCDVVNLTCEACQEPGG 479
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 17053331 unique seqs, 1923837318 residues
Total number of hits satisfying chosen parameters: 17053331
Minimum DB seq length: 0
Maximum DB seq length: 2000000000
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 150 summaries
Database : Published_Applications_AA_Main:*
ALIGNMENT:
Query Match 100.0%; Score 2709; Length 2813;
Best Local Similarity 100.0%;
Matches 479; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SLSCRPPMVKLVCPADNLRAEGLECTKTCQNYDLECMSMGCVSGCLCPPGMVRHENRCVA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 764 SLSCRPPMVKLVCPADNLRAEGLECTKTCQNYDLECMSMGCVSGCLCPPGMVRHENRCVA 823
Qy 61 LERCPCFHQGKEYAPGETVKIGCNTCVCRDRKWNCTDHVCDATCSTIGMAHYLTFDGLKY 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 824 LERCPCFHQGKEYAPGETVKIGCNTCVCRDRKWNCTDHVCDATCSTIGMAHYLTFDGLKY 883
Qy 121 LFPGECQYVLVQDYCGSNPGTFRILVGNKGCSHPSVKCKKRVTILVEGGEIELFDGEVNV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 884 LFPGECQYVLVQDYCGSNPGTFRILVGNKGCSHPSVKCKKRVTILVEGGEIELFDGEVNV 943
Qy 181 KRPMKDETHFEVVESGRYIILLLGKALSVVWDRHLSISVVLKQTYQEKVCGLCGNFDGIQ 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 944 KRPMKDETHFEVVESGRYIILLLGKALSVVWDRHLSISVVLKQTYQEKVCGLCGNFDGIQ 1003
Qy 241 NNDLTSSNLQVEEDPVDFGNSWKVSSQCADTRKVPLDSSPATCHNNIMKQTMVDSSCRIL 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1004 NNDLTSSNLQVEEDPVDFGNSWKVSSQCADTRKVPLDSSPATCHNNIMKQTMVDSSCRIL 1063
Qy 301 TSDVFQDCNKLVDPEPYLDVCIYDTCSCESIGDCACFCDTIAAYAHVCAQHGKVVTWRTA 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1064 TSDVFQDCNKLVDPEPYLDVCIYDTCSCESIGDCACFCDTIAAYAHVCAQHGKVVTWRTA 1123
Qy 361 TLCPQSCEERNLRENGYECEWRYNSCAPACQVTCQHPEPLACPVQCVEGCHAHCPPGKIL 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1124 TLCPQSCEERNLRENGYECEWRYNSCAPACQVTCQHPEPLACPVQCVEGCHAHCPPGKIL 1183
Qy 421 DELLQTCVDPEDCPVCEVAGRRFASGKKVTLNPSDPEHCQICHCDVVNLTCEACQEPGG 479
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1184 DELLQTCVDPEDCPVCEVAGRRFASGKKVTLNPSDPEHCQICHCDVVNLTCEACQEPGG 1242
US-15-576-055-4
Filing date in PALM: 2017-11-21
Sequence 4, US/15576055
Publication No. US20180161402A1
GENERAL INFORMATION
APPLICANT: CSL Behring Recombinant Facility AG
TITLE OF INVENTION: Truncated von Willebrand factor polypeptides for treating
TITLE OF INVENTION: hemophilia
FILE REFERENCE: 06478.1631-00000
CURRENT APPLICATION NUMBER: US/15/576,055
CURRENT FILING DATE: 2017-11-21
PRIOR APPLICATION NUMBER: PCT/EP2016/061443
PRIOR FILING DATE: 2016-05-20
PRIOR APPLICATION NUMBER: EP 15168930.4
PRIOR FILING DATE: 2015-05-22
PRIOR APPLICATION NUMBER: EP 16163239.3
PRIOR FILING DATE: 2016-03-31
NUMBER OF SEQ ID NOS: 8
SEQ ID NO 4
LENGTH: 2813
TYPE: PRT
ORGANISM: Homo sapiens
Regarding claim 14, Schulte teaches wherein the truncated VWF lacks amino acids 1243 to 2813 of SEQ ID NO:4 (“the truncated VWF consists of (a) amino acids 764 to 1242 of SEQ ID NO:4”, paragraph [0131]).
Regarding claim 15, Schulte teaches wherein the truncated VWF consists of
(a) amino acids 764-1242 of SEQ ID NO: 4 (“the truncated VWF consists of (a) amino acids 764 to 1242 of SEQ ID NO:4”, paragraph [0131]), or
(b) an amino acid sequence having a sequence identity of at least 90% to amino acids 764 to 1242 of SEQ ID NO:4 (“the truncated VWF consists of (a) an amino acid sequence having a sequence identity of at least 90% to amino acids 764 to 1242 of SEQ ID NO:4”; paragraph [0131]), or
(c) a fragment of (a) or (b) (paragraph [0131]).
Regarding claim 16, Schulte teaches wherein the truncated VWF does not comprise the binding sites for platelet glycoprotein 1bα (GP1bα), collagen, and /or integrin α11bβIII (RGDS sequence within the C1 domain) (paragraph [0168]).
Regarding claim 18, Schulte teaches wherein the polypeptide does not contain the VWF domains A1 and/or A3 or a part thereof (paragraph [0168]).
Regarding claim 19, Schulte teaches wherein the polypeptide is a fusion protein comprising the truncated VWF and a half-life extending polypeptide (paragraph [0175]).
Regarding claim 20, Schulte teaches wherein the half-life extending polypeptide is albumin or a fragment thereof (paragraph [0177]).
Regarding claim 21, Schulte teaches wherein the composition is a formulation (paragraph [0246]).
Schulte does not expressly teach storing the composition (instant claim 1).
While Schulte does not expressly teach storingthe composition (instant claim 1), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined Schulte’s method with Schulte’s teachings on storage of a therapeutic formulation of a truncated VWR, to have modified Schulte’s method for increasing the in vitro stability of coagulation factor VIII (FVIII) in a composition, wherein the method comprises storing the composition. One would have been motivated to do so, in order to have a composition ready and available for administering when needed (paragraph [0241]). A skilled artisan would have reasonably expected success since Schulte teaches increased in vitro stability of FVIII in the presence of VWR fragments (paragraph [0012]).
Regarding claim 17, modified Schulte teaches the claimed method and composition. Therefore, Schulte’s polypeptide would have the same or similar properties as the instant polypeptide, i.e. the same or similar dissociation constant KD, for binding of the polypeptide to GPIbα.
Regarding claim 18, modified Schulte teaches the claimed method and composition. Therefore, Schulte’s polypeptide would have the same or similar properties as the instant polypeptide, i.e. the same or similar dissociation constant for binding of the polypeptide to collagen type I and type III.
Claims 1, 7-11, 26-28, and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Schulte et al. (US 2018/0161402 A1, published on 06/14/2018), hereinafter ‘Schulte’, in view of Kannicht et al. (US 2018/0185455 A1, published on 07/05/2018), hereinafter ‘Kannicht’.
Schulte’s teachings have been set forth above
Regarding claim 26, pertaining to a method for increasing the in vitro stability of coagulation factor VIII (FVIII) in a composition, Schulte teaches mixing a polypeptide comprising a truncated von Willebrand Factor (VWF) and said FVIII to form a composition comprising the FVIII and the polypeptide comprising said truncated VWF (paragraphs [0241], [0014], [0082]; see claim 30), wherein the molar ratio of the polypeptide to the FVIII in the composition is greater than 20 (paragraph [0016], see claim 30).
Additionally, Schulte teaches storage of therapeutic formulations of a truncated von Willebrand Factor (VWF) (paragraphs [0014] and [0246]), wherein VWR fragments increase the in vitro stability of FVIII (paragraph [0012]), and preparing therapeutical compositions comprising a truncated VWR in lyophilized or aqueous form for storage (paragraph [0246], [0014]).
Regarding claim 31, Schulte teaches wherein the molar ratio is at least 200 (paragraph [0018]).
Modified Schulte does not teach
freeze-drying and reconstituting the composition (instant claim 7),
reconstituting the freeze-dried composition immediately after freeze-drying (instant claim 8),
storage of a freeze-dried composition at 25 °C (instant claim 9),
wherein storage is for a period of 12 months (instant claim 10),
storage of a liquid composition comprising a polypeptide comprising a truncated VWF and FVIII at 25 °C for one week (instant claim 11),
freeze-drying the composition; storing the freeze-dried composition; and reconstituting the freeze-dried composition (instant claim 26),
wherein storing is for at least 12 months (instant claim 27),
wherein storing is for at least 6 months (instant claim 28).
Kannicht’s general disclosure relates to a composition comprising a complex of Factor VIII and one or more Von Willebrand Factor peptides (see entire document, including abstract).
Regarding claim 7, Kannicht teaches freeze-drying and reconstituting of a composition comprising Factor VIII and Von Willebrand Factor (VWF) fragments (paragraphs [0018], [0027], [0295], [0298]-[0299], [0352]).
Regarding claim 8, pertaining to reconstituting immediately after freeze-drying, Kannicht teaches wherein a freeze-dried composition is stored for 12 months (paragraph [0299]). The Examiner notes that a storage time of 12 months includes any storage time up to 12 months.
Regarding claim 9, Kannicht teaches storage of a freeze-dried composition at 25 °C (paragraph [0299]).
Regarding claim 10, Kannicht teaches storage of the composition is for a period of 12 months (paragraph [[0299]).
Regarding claim 11, Kannicht teaches a liquid composition comprising FVIII and a VWR fragment (paragraph [0297], [0352]), and further teaches storing a VWR fragment/FVIII composition at 25 °C for 12 months (paragraph [0299]). The Examiner notes that a storage time of 12 months includes a storage time of one week.
Regarding claim 26, Kannicht teaches storage of a freeze-dried composition comprising FVIII and a VWR fragment (paragraphs [0018], [0295], [0298]-[0299]), and further teaches reconstituting a composition comprising FVIII and added VWF fragment (paragraphs [0297], [0352]).
Regarding claims 27-28, Kannicht teaches a storage time of a composition comprising FVIII and VWR fragments of 12 months and 24 months (paragraphs [0297]-[0299]).
While modified Schulte does not teach freeze-drying and reconstituting the composition (instant claim 7), storage of a freeze-dried composition at 25 °C (instant claim 9), wherein storage is for a period of 12 months (instant claim 10), storage of a liquid composition comprising a polypeptide comprising a truncated VWF and FVIII at 25 °C for one week (instant claim 11), and wherein storing is for at least 6 months (instant claim 28), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined modified Schulte’s method with Kannicht’s teachings on freeze-drying, reconstituting, and storing a composition comprising FVIII and VWR fragments, in order to have created a method comprising freeze-drying and reconstituting the composition (instant claim 7), storage of a freeze-dried composition at 25 °C (instant claim 9) wherein storage is for a period of 12 months (instant claim 10), storage of a liquid composition comprising a polypeptide comprising a truncated VWF and FVIII at 25 °C for one week (instant claim 11), and storing for 12 months or 24 months (instant claim 28). One would have been motivated to do so in order to identify optimal storage conditions for the composition comprising a polypeptide comprising a truncated VWF and FVIII that allow for maximal stability of FVIII activity.
While modified Schulte does not teach reconstituting the freeze-dried composition immediately after freeze-drying (instant claim 8), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined modified Schulte’s method with Kannicht’s teachings on storage periods of 12 and 24 months, to have reconstituted the composition at any time after freeze-drying. One would have been motivated to do so in order to investigate the impact of both freeze-drying and storage on FVIII activity.
While Schulte does not teach freeze-drying the composition, storing the freeze-dried composition, and reconstituting the freeze-dried composition (instant claim 26), wherein storing is for at least 12 months (instant claim 27), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to have modified Schulte’s method with Kannicht’s teachings on freeze-drying, reconstituting, and storing a composition comprising FVIII and VWR fragments, in order to have created a method that comprises freeze-drying the composition, storing the freeze-dried composition and reconstituting the freeze-dried composition (instant claim 26) wherein storing is for 12 or 24 months (instant claim 27). One would have been motivated to do so, in order to prepare a composition that is ready and available for administering when needed (see Schulte, paragraph [0241]).
A skilled artisan would have reasonably expected success in combining Schulte’s and Kannicht’s teachings since both are directed to compositions comprising VWR fragments and FVIII.
Regarding claims 7, 9, and 11, pertaining to FVIII, Schulte in view of Kannicht teaches the claimed method and composition. As such, it is the Examiner’s position that modified Schulte’s method results in the same FVIII yield and FVIII activity as the claimed method, and therefore results in a greater yield of FVIII (instant claim 7), lower loss of FVIII activity (instant claim 9), and a greater FVIII activity (instant claim 11) in a composition with a polypeptide comprising truncated VWR versus in a composition without the polypeptide under the described conditions.
Claims 23-25, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Kannicht et al. (US 2018/0185455 A1, published on 07/05/2018), hereinafter ‘Kannicht’, in view of Schulte et al. (US 2018/0161402 A1, published on 06/14/2018), hereinafter ‘Schulte’.
Kannicht’s general disclosure relates to a composition comprising a complex of Factor VIII and one or more Von Willebrand Factor peptides (see entire document, including abstract).
Regarding claim 23, pertaining to a method of storing a pharmaceutical composition, Kannicht teaches a method of storing a pharmaceutical composition comprising coagulation factor VIII (FVIII) and a truncated von Willebrand Factor (VWF) (paragraphs [0018], [0024], [0027]-[0028], [0302]-[0303]), said method comprising: storing the composition for a time period of 12 months and 24 months (paragraphs [0295], [0297]-[0299], [0302]).
Regarding claim 24, Kannicht teaches wherein the composition is in a freeze-dried form (paragraphs [0298]-[0299]).
Regarding claim 25, Kannicht teaches wherein the composition is stored at a temperature of 25 °C (paragraph [0299]).
Kannicht does not teach wherein the molar ratio of the polypeptide to the FVIII in the composition is greater than 20 (instant claim 23), or wherein the molar ratio is at least 200. (instant claim 30).
Schulte’s general disclosure relates to relates to a polypeptide comprising a truncated von Willebrand Factor (VWF) for use in the treatment of a blood coagulation disorder, wherein the polypeptide carries a half-life extending moiety and is administered in molar excess over Factor VIII and/or endogenous VWF (see entire document, including abstract).
Regarding claims 23 and 30, pertaining to the molar ratio, Schulte teaches a pharmaceutical composition comprising a polypeptide comprising a truncated von Willebrand Factor (VWF) and FVIII (paragraph [0082], see Schulte’s claim 30), wherein the molar ratio of the polypeptide to the FVIII in the composition is greater than 20 (“greater than about 50”; paragraph [0016], see Schulte’s claim 30), and wherein said molar ratio is at least 200 (paragraph [0018]).
While Kannicht does not teach wherein the molar ratio of the polypeptide to the FVIII in the composition is greater than 20 (instant claim 23), or wherein the molar ratio is at least 200. (instant claim 30), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined Kannicht’s teachings on a storage method with Schulte’s teachings on molar ratio, to have created a storage method for a composition comprising coagulation factor VIII (FVIII) and a truncated VWF, wherein the molar ratio of the truncated VWF to FVIII is greater than 50, and wherein the molar ratio is at least 200. One would have been motivated to do so to improve the stability of FVIII during storage, since truncated VWF stabilizes FVIII (see Kannicht, paragraph [0302]; see Schulte, paragraph [0012]). A skilled artisan would have reasonably expected success in combining Kannicht’s and Schulte’s teachings since both are directed to compositions comprising VWR fragments and FVIII.
Response to Arguments
Applicant has traversed the previous prior art rejections in the reply filed on 06/10/2025. Schulte’s and Kannicht’s teachings are still relied upon. Applicant's arguments have been fully considered but they are not persuasive.
In Applicant’s reply, Applicant states that Schulte “is based on the finding that a high molar excess of truncated VWF over FVIII increases the in vivo half-life of FVIII”, further that Schulte “merely suggests mixing truncated VWF and FVIII immediately prior to administration”, and that Schulte teaches “co-administration of the individual active agents (i.e. separately, not as a mixture) does not in any way suggest mixing” (remarks, page 7 and 8).
The Examiner responds that regarding claim 22, Schulte teaches the method and composition recited in the claim. As such, Schulte’s coagulation factor VIII is expected to have the same properties, i.e. increased in vitro stability. Schulte teaches a pharmaceutical composition comprising FVIII and a polypeptide comprising a truncated VWR (see Schulte’s claim 30) which inherently requires mixing of the components.
Applicant describes that based on Schulte’s teachings and known techniques, a skilled artisan would not be motivated to lyophilize and store a mixture of FVIII and a VWF fragment and that “Kannicht does not anywhere teach or suggest the compositions of the present invention having a great excess of VWF as compared to Factor VIII” (remarks, page 8).
In response to Applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, regarding base claims 1, 23, and 26, Schulte teaches a method that provides the instant composition and the recited molar ratio, and Kannicht teaches lyophilizing, storing, and reconstituting the cited composition.
Applicant describes wherein Example 4 describes unexpected results (remarks, page 9).
The Examiner responds that the significance of the impact of the molar ratio on the % loss of FVIII is unclear since no statistical evaluation of the presented data in the instant application is provided (see specification, Table 4 ), and therefore, proper interpretation of the presented results is not possible (see MPEP 716.02(b) I). It is further noted that results of decreased loss of FVIII are expected since Schulte teaches that “VWF-derived polypeptides, in particular VWF fragments, have been described to stabilize FVIII in vitro” (paragraph [0012]), and Kannicht teaches wherein “Von Willebrand Factor peptides seem to increase stability of Factor upon storage (shelf-life)” (paragraph [0302]).
Conclusion
No claims are allowed.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SANDRA ZINGARELLI whose telephone number is (703)756-1799. The examiner can normally be reached M-F 9-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila 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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/SANDRA ZINGARELLI/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/ Supervisory Patent Examiner, Art Unit 1653