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 .
Claim Status
The amendment of 08/04/2026 has been entered. Claims 1-21, 23-28, 30-36 are pending (claim set as filed on 08/04/2026). Claims 1-21, 23-28, 30-36 are currently under examination and were examined on their merits.
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed on 06/05/2026 has been received and considered.
Withdrawn Objections/Rejections
The objection of claim 13, the rejection of claims 17-18, 22-25 and 29-31 under 35 U.S.C. 112(b) and the rejection of claims 22 and 29 under 35 U.S.C. 102 as set forth in the previous Office action are withdrawn in light of Applicant’s amendment filed on 08/04/2026.
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 34-36 are newly rejected as necessitated by amendment 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 34-36 recite “the truncated VWF of SEQ ID NO:4” which is indefinite for lacking antecedent basis because “the truncated VWF of SEQ ID NO:4” is not recited within the claim or in claims 1, 23, and 26 from which claims 34-36 depend, respectively. It is further unclear if “the truncated VWF of SEQ ID NO:4” means that the truncated VWF consists of SEQ ID NO:4, or if the truncated VWF corresponds to a part of SEQ ID NO: 4. One of ordinary skill in the art would not be able to determine the metes and bounds of the claim, and thus, could not clearly determine how to avoid infringement of claims 34-36.
In the interest of compact prosecution, claims 34-36 are interpreted to the broadest embodiment claimed.
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, 12-21, and 32-34 are newly rejected as necessitated by amendment 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, 17 and 32, 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]).
Regarding claim 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 claims 18 and 33, 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]).
Regarding claim 34, please note the rejection under Claim Rejections - 35 USC § 112 (b) above. Pertaining to the polypeptide, Schulte teaches wherein the polypeptide is a fusion protein comprising a truncated VWF of SEQ ID NO: 4 and albumin (paragraphs [0014], [0131], [0175], [0177]), and wherein the molar ratio of the polypeptide to FVIII in the composition is greater than 200 (paragraphs [0116], and [0241]). As discussed above regarding claims 13 and 15, Schulte teaches wherein the truncated VWF consists of amino acids 764-1242 of the instant SEQ ID NO: 4 (paragraph [0131]; see alignment above; note, amino acids 764-1242 of Applicant’s SEQ ID NO:4 correspond to Qy 1-479). 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.
Schulte does not expressly teach storing the composition (instant claim 1).
While Schulte does not expressly teach storing the 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 claims 17 and 32, 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 claims 18 and 33, 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, 31, and 36 are newly rejected as necessitated by amendment 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]).
Regarding claim 36, please note the rejection under Claim Rejections - 35 USC § 112 (b) above. Pertaining to the polypeptide, Schulte teaches wherein the polypeptide is a fusion protein comprising a truncated VWF of SEQ ID NO: 4 and albumin (paragraphs [0014], [0131], [0175], [0177]), and wherein the molar ratio of the polypeptide to FVIII in the composition is greater than 200 (paragraphs [0116], and [0241]). As discussed above regarding claims 13 and 15, Schulte teaches wherein the truncated VWF consists of amino acids 764-1242 of the instant SEQ ID NO: 4 (paragraph [0131]; see alignment above; note, amino acids 764-1242 of Applicant’s SEQ ID NO:4 correspond to Qy 1-479). 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.
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 VWF versus in a composition without the polypeptide under the described conditions.
Claims 23-25, 30, and 35 are newly rejected as necessitated by amendment 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 polypeptide comprising 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), wherein the molar ratio is at least 200. (instant claim 30), or wherein said polypeptide is a fusion protein comprising the truncated VWF of SEQ ID NO:4 and albumin and wherein the molar ratio of the polypeptide to the FVIII in the composition is greater than 200 (instant claim 35).
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]).
Regarding claim 35, please note the rejection under Claim Rejections - 35 USC § 112 (b) above. Pertaining to the polypeptide, Schulte teaches wherein the polypeptide is a fusion protein comprising a truncated VWF of SEQ ID NO: 4 and albumin (paragraphs [0014], [0131], [0175], [0177]), and wherein the molar ratio of the polypeptide to FVIII in the composition is greater than 200 (paragraphs [0116], and [0241]). As discussed above regarding claims 13 and 15, Schulte teaches wherein the truncated VWF consists of amino acids 764-1242 of the instant SEQ ID NO: 4 (paragraph [0131]; see alignment above; note, amino acids 764-1242 of Applicant’s SEQ ID NO:4 correspond to Qy 1-479). 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.
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]).
While Kannicht does not teach wherein the polypeptide is a fusion protein comprising the truncated VWF of SEQ ID NO:4 and albumin and wherein the molar ratio of the polypeptide to the FVIII in the composition is greater than 200 (instant claim 35), 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 Kannicht’s storage method of a pharmaceutical composition with Schulte’s teachings on a fusion protein and molar ratio, to create a storage method wherein said polypeptide is a fusion protein comprising the truncated VWF of SEQ ID NO:4 and albumin and wherein the molar ratio of the polypeptide to the FVIII in the composition is greater than 200. One would have been motivated to use Schulte’s fusion protein to increase the half-life of the truncated VWR since albumin is a half-life extending protein (Schulte, paragraph [0177]). One would have been motivated to employ a molar ratio of polypeptide to FVIII that is greater than 200 as taught by Schulte to ensure stability of FVIII during storage and after administration, since truncated VWF stabilizes FVIII in vitro and in vivo (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 08/04/2026. 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: “[T]he Examiner has erroneously assumed that Schulte' s teachings directed to co-administration to improve in vivo half-life characteristics are transferable to an in vitro context. Such assumption is not valid. There is no teaching or suggestion in Schulte that a truncated VWF polypeptide fused to a half-life extension moiety such as albumin would have a positive improvement on stability of Factor VIII in an in vitro environment. One skilled in the art certainly could not have predicted the improved results for the present invention as shown in the present application with any reasonable expectation of success based on the teachings in Schulte” (remarks, page 12).
The Examiner responds that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the reference or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, regarding base claim 1, Schulte teaches the claimed composition, the recited molar ratio, and motivation to store said composition. It is noted that Schulte’s composition inherently requires mixing of the components (see claim 30 and paragraph [0241]). It would have been obvious to a skilled artisan to have combined Schulte’s teachings to have arrived at the instant method for increasing the in vitro stability of FVIII. One would have been motivated to do so to have a composition ready and available for administering when needed (Schulte, paragraph [0241]). Since Schulte teaches the method, composition and molar ratio recited in the claim, coagulation factor VIII in Schulte’s composition is expected to have the same properties, i.e. increased in vitro stability.
Applicant describes that combining the references Schulte and Kannicht as suggested by the Examiner is improper hindsight (remarks, page 15).
The Examiner responds that it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In this case, regarding base claims 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. Regarding claim 23, it would have been obvious to a skilled artisan to have combined Kannicht’s and Schulte’s teachings to increase the stability of FVIII during storage since truncated VWF stabilizes FVIII (Kannicht, paragraph [0302]). Regarding claim 26, it would have been obvious to a skilled artisan to have combined Schulte’s and Kannicht’s teachings to prepare a composition that is ready and available for administering when needed (see Schulte, paragraph [0241]).
Applicant describes wherein the results of decreased loss of FIII activity described in Examples 3 and 4 in the specification are unexpected (remarks, pages 16-19).
The Examiner responds that results showing a decreased loss of FVIII activity 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.
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.
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.
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/SANDRA ZINGARELLI/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
