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 .
Priority
This application is a CON of 16/415,893 filed 05/17/2019 now Patent 12030925. 16/415,893 has PRO 62/801,576 filed 02/05/2019. 16/415,893 has PRO 62/773,785 filed 11/30/2018, PRO 62/712,880 filed 07/31/2018, and PRO 62/673,670 filed 05/18/2018.
Information Disclosure Statement
The information disclosure statements submitted on 05/07/2025 have been considered by the examiner.
Claim Status
Claims 90-104 are being examined on the merits in this office action.
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 90-95, and 104 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Seth et al. (WO 2015/106052A1 - hereinafter “Seth”).
Regarding claim 90, Seth teaches a chimeric protein comprising: i) a FVIII protein and ii) a VWF protein (claim 1) and that the proteins are linked by a disulfide bond ([0221] and claim 29). Seth further teaches that the chimeric protein comprises a VWF polypeptide comprising amino acid sequence of SEQ ID No: 197 which comprises the instant SEQ ID NO: 202. Furthermore, Seth discloses on pages 173-174 the FVIIII comprising the amino acid sequence of SEQ ID NO: 173 (page 173-174), which comprises the instant SEQ ID NO: 207.
Seth further teaches the composition for use in a subject suffering from Hemophilia A [0043, 0106] with a dose of 37.5 IU/kg, 75 IU/kg, [0051, 0349, 0363] which is comprised in the instantly claimed range and that several divided doses may be administered over time [0283]. Seth further teaches that the chimeric protein can be administered as a prophylactic or on-demand ([0041, 0043, 0108, 0292, 0313, 0315] and claim 130) and further teaches that the administration of the polypeptide is intravenous or subcutaneous administration ([0040] and claim 120). It is clear that the chimeric protein of FVIII and VWF comprising the instant SEQ ID NOS: 207 and 202 respectively, is known in the art and disclosed for use in the treatment of bleeding disorders such as Hemophilia.
Regarding claims 91-92, Seth teaches that the chimeric polypeptide can be administered as a single bolus or several divided doses [0283].
Regarding claim 93-94, Seth teaches that the chimeric polypeptide may be given prior to activities that increase the risk of bleeding, such as contact sports [0108].
Regarding claim 95, Seth teaches that the subject is a human [0043].
Regarding claim 104, Seth teaches a chimeric protein comprising: i) a FVIII protein and ii) a VWF protein (claim 1) and that the proteins are linked by a disulfide bond ([0221] and claim 29), and teaches a method for treating a bleeding disorder such as hemophilia A (claim 122, 126, 129; [0106, 0292-0293, 0306-0311, 0316, 0352]). Seth teaches that the subject is scheduled to undergo surgery or is undergoing surgery [0041, 0107, 0292, 0313]. Seth further teaches that the chimeric protein comprises a VWF polypeptide comprising amino acid sequence of SEQ ID No: 197 which comprises the instant SEQ ID NO: 202. Furthermore, Seth discloses on pages 173-174 the FVIIII comprising the amino acid sequence of SEQ ID NO: 173 (page 173-174), which comprises the instant SEQ ID NO: 207. Seth further teaches the composition for use in a subject suffering from Hemophilia A [0043, 0106] with a dose of 37.5 IU/kg37.5 IU/kg, 75 IU/kg [0051, 0349, 0363] which is comprised in the instantly claimed range and that several divided doses may be administered over time [0283]. Seth teaches that the subjects are treated with a single intravenous administration [0347]. Seth further teaches that the chimeric protein can be administered as a prophylactic or on-demand ([0041, 0043, 0108, 0292, 0313, 0315] and claim 130) and further teaches that the administration of the polypeptide is intravenous or subcutaneous administration ([0040] and claim 120). It is clear that the chimeric protein of FVIII and VWF comprising the instant SEQ ID NOS: 207 and 202 respectively, is known in the art and disclosed for use in the treatment of bleeding disorders such as Hemophilia.
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 96-103 are rejected under 35 U.S.C. 103 as being unpatentable over Seth et al. (WO 2015/106052A1 - hereinafter “Seth”) as applied to claim 90 above, and further in view of Franchini et al. (Ann Hematol (2007) 86:699–704).
The teachings of Seth are disclosed above and incorporated herein by reference. Seth does not teach at least twelve bleeding episodes as recited in claim 97.
Franchini teaches a method of treating bleeding episodes comprising administering VIII/VWF concentrate and that the concentrate is administered at 20–50 IU/kg of FVIII/VWF once daily and that it was effective in preventing bleeding in more than 90% of surgical or invasive procedures (Page 701, left col., 5th paragraph, line 1-6). Franchini further teaches the concentrate administered to subjects that had twelve bleeding episodes with 93% excellent or good efficacy and no adverse events (Page 701, left col., 2nd paragraph, line 1-7). Franchini further teaches prophylactic treatment with the concentrate at least once per week for 45 weeks (about 11 months) (Page 702, left col., line 1-4). Examiner notes that the teaching reads on at least three months.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Seth and administer the chimeric protein to subjects that had twelve bleeding episodes since Franchini teaches that such a polypeptide has been administered to such subjects and had 93% excellent or good efficacy and no adverse events (Page 701, left col., 2nd paragraph, line 1-7). One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in administering the chimeric protein to the patient population taught by Franchini since such concentrate has been administered to subjects with at least 12 bleeding episodes at a higher success rate.
Regarding claim 96, Seth teaches that the subject were treated with FVIII product which does not comprise VWF fragment [0053, 0054, 0354].
Regarding claim 97, Franchini teaches the concentrate administered to subjects that had twelve bleeding episodes with 93% excellent or good efficacy and no adverse events (Page 701, left col., 2nd paragraph, line 1-7). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Seth and administer the chimeric protein to subjects that had twelve bleeding episodes since Franchini teaches that such a polypeptide has been administered to such subjects and had 93% excellent or good efficacy and no adverse events (Page 701, left col., 2nd paragraph, line 1-7).
Regarding claim 98, Franchini teaches a method of treating bleeding episodes comprising administering VIII/VWF concentrate and that the concentrate is administered at 20–50 IU/kg of FVIII/VWF once daily and that it was effective in preventing bleeding in more than 90% of surgical or invasive procedures (Page 701, left col., 5th paragraph, line 1-6). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Seth and administer the chimeric protein at a dose 50 IU/kg since Franchini teaches that the administration of the polypeptide at the taught dose was effective in treating bleeding episodes.
Regarding claim 99, Seth teaches a chimeric protein comprising: i) a FVIII protein and ii) a VWF protein (claim 1) and that the proteins are linked by a disulfide bond ([0221] and claim 29). Seth further teaches that the chimeric protein comprises a VWF polypeptide comprising amino acid sequence of SEQ ID No: 197 which comprises the instant SEQ ID NO: 202. Furthermore, Seth discloses on pages 173-174 the FVIIII comprising the amino acid sequence of SEQ ID NO: 173 (page 173-174), which comprises the instant SEQ ID NO: 207. Seth further teaches the composition for use in a subject suffering from Hemophilia A [0043, 0106] with a dose of 37.5 IU/kg [0051, 0349, 0363] which is comprised in the instantly claimed range and that several divided doses may be administered over time [0283]. Examiner notes that this teaching reads on at least 3 months. Seth teaches that the subjects are treated with a single intravenous administration [0347]. Seth further teaches that the chimeric protein can be administered as a prophylactic or on-demand ([0041, 0043, 0108, 0292, 0313, 0315] and claim 130) and further teaches that the administration of the polypeptide is intravenous or subcutaneous administration ([0040] and claim 120). It is clear that the chimeric protein of FVIII and VWF comprising the instant SEQ ID NOS: 207 and 202 respectively, is known in the art and disclosed for use in the treatment of bleeding disorders such as Hemophilia. Additionally, Franchini teaches prophylactic treatment with the concentrate at least once per week for 45 weeks (about 11 months) (Page 702, left col., line 1-4). Examiner notes that the teaching reads on at least three months. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Seth and administer the chimeric protein to subjects at the duration taught by Franchini since the method successfully treated bleeding episodes.
Regarding claims 100-103, Franchini teaches prophylactic treatment with the concentrate at least once per week for 45 weeks (about 11 months) (Page 702, left col., line 1-4). Examiner notes that the teaching reads on at least three months. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Seth and administer the chimeric protein to subjects at the duration taught by Franchini since the method successfully treated bleeding episodes.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 90-104 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 11, 14-17 of U.S. Patent No. US12030925B2 in view of Seth et al. (WO 2015/106052A1 - hereinafter “Seth”). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the patent recite a method of treating hemophilia A comprising administering multiple doses of a chimeric polypeptide at a dosing interval to a human subject in need thereof, wherein the chimeric polypeptide comprises:
(i) a FVIII protein comprising the amino acid sequence of SEQ ID NO: 207; and
(ii) a VWF protein comprising the amino acid sequence of SEQ ID NO: 202; wherein each of the multiple doses is from 45 IU/kg to 55 IU/kg and the dosing interval is at least 6 days to 8 days; and wherein the multiple doses are administered for at least about 6 months; wherein the chimeric polypeptide is administered for prophylactic treatment; wherein the chimeric polypeptide is administered intravenously.
The claims of the patent do not recite the method for on-demand treatment.
Seth teaches a chimeric protein comprising: i) a FVIII protein and ii) a VWF protein (claim 1) and that the proteins are linked by a disulfide bond ([0221] and claim 29). Seth further teaches that the chimeric protein comprises a VWF polypeptide comprising amino acid sequence of SEQ ID No: 197 which comprises the instant SEQ ID NO: 202. Furthermore, Seth discloses on pages 173-174 the FVIIII comprising the amino acid sequence of SEQ ID NO: 173 (page 173-174), which comprises the instant SEQ ID NO: 207. Seth further teaches the composition for use in a subject suffering from Hemophilia A [0043, 0106] with a dose of 37.5 IU/kg [0051, 0349, 0363] which is comprised in the instantly claimed range and that several divided doses may be administered over time [0283]. Examiner notes that this teaching reads on at least 3 months. Seth teaches that the subjects are treated with a single intravenous administration [0347]. Seth further teaches that the chimeric protein can be administered as a prophylactic or on-demand ([0041, 0043, 0108, 0292, 0313, 0315] and claim 130) and further teaches that the administration of the polypeptide is intravenous or subcutaneous administration ([0040] and claim 120).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method recited by the claims of the patent and use the method for on-demand therapy as taught by Seth so as to administer chimeric molecule in response to symptoms of a bleeding episode or before an activity that may cause bleeding. One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in administering the chimeric protein on-demand such as when bleeding starts so as to reduce the risk of bleeding. The disclosures render obvious claims 90, and 99.
Regarding claim 91, Seth teaches that the chimeric polypeptide can be administered as a single bolus or several divided doses [0283]. It would have been obvious to modify the method of patent and also administer the chimeric protein as a single dose.
Regarding claim 92, the claims of the patent recite wherein the multiple doses are administered for at least about 6 months (claim 1).
Regarding claim 93, Seth teaches that the chimeric polypeptide may be given prior to activities that increase the risk of bleeding, such as contact sports [0108]. It would have been obvious to modify the method of patent and also administer the chimeric protein before an activity that increases risk of bleeding such as physical trauma.
Regarding claim 95, the claims of the patent recite administering the chimeric polypeptide wherein the subject is a human (claim 1-2, 11).
Regarding claim 96, Seth teaches that the subject were treated with FVIII product which does not comprise VWF fragment [0053, 0054, 0354]. It would have been obvious to modify the method of patent and also administer the subject with FVIII product which does not comprise VWF fragment.
Regarding claim 97, the claims of the patent recite wherein the subject was previously on an on-demand treatment regimen with a marketed FVIII product and has had at least twelve bleeding episodes (claim 5).
Regarding claim 98, the claims of the patent recite wherein each of the multiple doses is 50 IU/kg (claim 3).
Regarding claims 100-103, the claims of the patent recite wherein the multiple doses are administered for at least about 6 months (claims 1-2, 11, 14-17).
Regarding claim 104, the claims of the patent recite a method of treating hemophilia A comprising administering multiple doses of a chimeric polypeptide at a dosing interval to a human subject in need thereof, wherein the chimeric polypeptide comprises:
(i) a FVIII protein comprising the amino acid sequence of SEQ ID NO: 207; and
(ii) a VWF protein comprising the amino acid sequence of SEQ ID NO: 202; wherein each of the multiple doses is from 45 IU/kg to 55 IU/kg and the dosing interval is at least 6 days to 8 days; and wherein the multiple doses are administered for at least about 6 months; wherein the chimeric polypeptide is administered for prophylactic treatment; wherein the chimeric polypeptide is administered intravenously.
The claims of the patent do not recite wherein the human subject is undergoing or will undergo surgery. However, Seth teaches that the subject is scheduled to undergo surgery or is undergoing surgery [0041, 0107, 0292, 0313]. It would have been obvious to modify the claims of the patent and administer the chimeric protein to a human subject who is undergoing or will undergo surgery as taught by Seth.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mercy H. Sabila whose telephone number is (571)272-2562. The examiner can normally be reached Monday - Friday 5:00 am - 3:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571)270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MERCY H SABILA/Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
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