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
Applicant’s election without traverse of Group I, claims 1-8 and 14-18 and SEQ ID NO: 56 as species in claim 7 in the reply filed on 11/12/2025 is acknowledged.
Attorney indicated that species for claims 2-6 are encompassed in elected SEQ ID NO:56 and elected "glycosylated" species for claim 8 in interview on January 30, 2026.
Species election for claims 2-6 is withdrawn.
Claims 9-13, 19 and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/12/2025.
Claims 1-8 and 14-18 (claim set filed 04/05/2023) are examined on the merits herein.
Priority
This application is a 371 of PCT/US2021/065588 filed 12/29/2021 which claims benefit of provisional application 63/107,678 filed 10/30/2020. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Drawings
The drawings are objected to because Fig. 1A and 1B have the following issues:
Fig. 1A and 1B display amino acid sequence alignment and have numbering for nucleic acid sequences which are not displayed. Applicant is suggested to have numbering for amino acids.
The first sequence in Figure 1A and 1B is the sequence of human FIX (SEQ ID NO:1) as described in the specification in Description of Figures (paragraph 0019). However, that sequence is different from the sequence with SEQ ID NO:1 (paragraph 0104 of the specification and sequence listing). The part of SEQ ID NO:1: “FNKGRSASVL” is displayed on Fig. 1B as: “FHKGRSALVL” (different amino acids are highlighted).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 recites acronym FIX. Although claim 1 is not rejected under 35 U.S.C. 112(b) since the specification describes that FIX is a clotting factor IX (paragraph 0002), to enhance the clarity of the claims aforesaid objection is made. The applicant is suggested to provide description of acronym FIX and use acronym later.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2-7 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 2-6 recite replacements of amino acid residues. The dual sequence numbering is explained in the specification as representing the replacement in the sequence with the signal peptide (first number) and without signal peptide (second number) (paragraph 0006). However, recitation of amino acid residues replacement has several uncertainty issues:
It is not clear how these residues can be identified. While claim 1 recites single replacement V132A-V86A identified by the alignment with SEQ ID NO:1 or SEQ ID NO:15 or sequences with 95% identity to SEQ ID NO:1 or SEQ ID NO:15, claims 2-6 do not provide reference SEQ ID NO for alignment. It is unclear if the same sequences can be used for identification since they are not mentioned.
The recited replacements indicate the amino acid residue to replace and not only its position. The unmodified FIX can have different residues in the aligned position and SEQ ID NO:1 or SEQ ID NO:15 (if used for alignment) do not have all the recited residues. For instance, position 361 has H and not N, position 366 has A and not L and position 367 has S and not V or L in SEQ ID NO:1. Therefore, it is not clear if replacement is performed for any residue aligned with that position (option 1) or replacement is performed only when the type of residue corresponds to the recited in claims 2-6 (option 2). For instance, if the residue aligned with position 313 in claim 2 is suggested to be replaced with S (option 1) or only when aligned position 313 has N, it is suggested to be replaced with S. The presence of two replacements of the same residue number, i.e. L367S-L321S and V367I-V321 in claim 2 seems to point to option 2.
Claim 2 recites: “comprising at least one amino acid replacements selected from among N313S-N267S, … and R404K-R358K”. Although reciting alternatives is not governed by a particular format, an issue of lack of clarity arises when it is not clear if the list of alternatives is closed or open. The transitional phrase “comprising” points to open group and the recitations “selected from” and “and” indicates closed group. The scope is unclear since it is not clear if applicant intends to make this a closed grouping “from the group consisting of” or an open group. Claims 3, 4, 5, 6 have the same issues.
Thus, the scope and boundaries of claims 2-6 are not certain making claims 2-6 indefinite.
Claim 7 recites the unmodified FIX to consist of sequences with SEQ ID NOS: 52-57. Claim 7 depends on claim 1 reciting modification of the unmodified FIX, i.e. V132A-V86A, resulting in a modified FIX. The sequences with SEQ ID NOS: 52-57 all have this replacement. It is not clear how sequences with SEQ ID NOS: 52-57 can be considered unmodified FIX if these polypeptides are modified according to claim 1. The scope and boundaries of claim 7 are not certain making claim 7 indefinite.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-6 and 18 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Gaucher (WO 2018208973 A1).
Regarding claim 1, Gaucher teaches novel variants of FVII, FVIII and FIX clotting factors with increased clotting factor activity relative to the corresponding native human clotting factor proteins (p. 1, lines 29-30). Figure 1 shows sequence alignment of variants with the sequence of human FIX with SEQ ID NO: 42 (p. 30, lines 16-24) which is 100% identical to instant SEQ ID NO: 1. Figure 1 presents multiple variants with replacement V132A (sequence with the signal peptide) or V86A (without the signal peptide). Gaucher teaches variant An96 fIX Padua with SEQ ID NO:1 (with the signal peptide) aligned with human FIX with sequence identical to instant SEQ ID NO:1 (p. 30) that has V132A replacement and which showed substantially more FIX activity compared to unmodified human FIX (p. 32, lines 19-24). Thus, Gaucher teaching anticipates claim 1.
Regarding claim 2, Gaucher teaches sequence of An96 fIX Padua that has N313S replacement (p. 30, SEQ ID NO:1) corresponding to limitation of claim 2. Thus, Gaucher teaching anticipates claim 2.
Regarding claim 3, Gaucher teaches sequence of An96 fIX Padua that has E323K replacement (p. 30, SEQ ID NO:1) corresponding to limitation of claim 3. Thus, Gaucher teaching anticipates claim 3.
Regarding claim 4, Gaucher teaches sequence of An96 fIX Padua that has D232N replacement (p. 30, SEQ ID NO:1) corresponding to limitation of claim 4. Thus, Gaucher teaching anticipates claim 4.
Regarding claim 5, Gaucher teaches sequence of An96 fIX Padua that has D338N replacement (p. 30, SEQ ID NO:1) corresponding to limitation of claim 5. Thus, Gaucher teaching anticipates claim 5.
Regarding claim 6, Gaucher teaches sequence of An96 fIX Padua that has R384L replacement (p. 30, SEQ ID NO:1) corresponding to limitation of claim 6. Thus, Gaucher teaching anticipates claim 6.
Regarding claim 18, Gaucher teaches An96 fIX Padua variant in a zymogen form (p. 6, lines 33-34). Thus, Gaucher teaching anticipates claim 18.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 7, 8 and 14-18 are rejected under 35 U.S.C. 103 as being unpatentable over Oyhenart (US 20080102115 A1).
Regarding claim 1, Oyhenart teaches modified FIX polypeptides (Abstract). The unmodified FIX is human FIX with SEQ ID NO: 1 for precursor form (with the signal peptide) and SEQ ID NO: 2 for the mature form (paragraph 0017). The SEQ ID NO: 1 of Oyhenart teaching has 99.6% identity to instant SEQ ID NO:1. Oyhenart discloses various modifications of FIX sequence and suggests more than one modification (paragraph 0012). Oyhenart describes that the modified FIX polypeptides exhibit increased activity compared to the unmodified FIX (paragraph 0024). Oyhenart suggests modifications that can reduce immunogenicity of FIX, one of such modifications is V132A-V86A (paragraph 0434).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to follow teaching of Oyhenart and create modified FIX incorporating V132A-V86A replacement. One would have been motivated to do that with since Oyhenart teaches that V132A-V86A modification reduces FIX immunogenicity and hence V132A-V86A modification can prevent formation of inhibitory antibodies and prolong modified FIX action in circulation. A skilled artisan would have reasonably expected success in that because Oyhenart teaches that more than one modifications of human FIX can be present and that suggested modifications exhibit increased FIX activity. Thus, Oyhenart teaching renders claim 1 obvious.
Regarding claim 7, Oyhenart teaches human FIX with SEQ ID NO:1. The SEQ ID NO:1 differs from instant SEQ ID NO:52 in 3 modifications, i.e. V138A-V86A, D338N-D292N and L367S-L321S. Oyhenart describes that modified FIX can include two or more modifications of positions, including recited positions V86, D292 and L321 in mature form and suggests replacement of D292N (paragraph 0013). Oyhenart discloses V138A-V86A and L367S-L321S modifications as modifications reducing immunogenicity of modified FIX (paragraph 0434). Combination of these three modifications will result in instant modified FIX with SEQ ID NO: 52.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to construct the modified FIX polypeptide comprising the sequence taught by Oyhenart and try combination of substitutions V138A-V86A, D338N-D292N and L367S-L321S. One would have been motivated to do that with reasonably expected success since Oyhenart provides instructions for modification and evaluation of FIX polypeptides, teaches that V86, D292 and L321 modifications can be combined and that V132A-V86A and L367S-L321S modifications reduces FIX immunogenicity and therefore the combination of V138A-V86A, D338N-D292N and L367S-L321S can improve therapeutic properties of FIX. Thus, Oyhenart teaching renders claim 7 obvious.
Regarding claims 8 and 14, Oyhenart teaches that the modified FIX polypeptides can be post-translationally modified, including “glycosylation, carboxylation, hydroxylation, sulfation, phosphorylation, or conjugation to albumin or polyethylene glycol (PEG) moiety” (paragraph 0022). Thus, Oyhenart teaching renders claims 8 and 14 obvious.
Regarding claim 15, Oyhenart teaches that the modified FIX polypeptides can include hyperglycosylation (paragraph 0426). Thus, Oyhenart teaching renders claim 15 obvious.
.
Regarding claims 16, 17 and 18, Oyhenart teaches that FIX polypeptides include precursor forms and mature forms, zymogens and activated forms (paragraph 0404). Thus, Oyhenart teaching renders claims 16, 17 and 18 obvious.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIOUBOV G KOROTCHKINA whose telephone number is (571)270-0911. The examiner can normally be reached Monday-Friday: 8:00-5:30.
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 G 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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/L.G.K./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653