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 DIV of 16/317,283 filed 01/11/2019 now PAT 11976106. 16/317,283 is a 371 of PCT/IL2017/050784 filed 07/11/2017. PCT/IL2017/050784 has PRO 62/360,767 filed 07/11/2016.
Information Disclosure Statement
The information disclosure statements submitted on 01/03/2025 and 01/21/2025 have been considered by the examiner.
Claim Status
Claims 38-59 are being examined on the merits in this office action
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 contains periods after limitations “I. – VII. And a-d.”. Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995); See also MPEP § 608.01(m). The examiner suggests using parenthesis instead, e.g., “…(I) stably transfecting…”. 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 38-59 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.
Claim 38 recites the limitation "…desired concentration…" in part (VII). The specification does not define what the desired concentration and how that concentration is distinguished from what is not desired. Thus, one of ordinary skill in the art would not be able to ascertain what the “desired concentration” and therefore the metes and bounds are unknowable. Claims 39-59 depend on the rejected claim 38 and are rejected as well.
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 38-42, 48-51, 54, and 56-59 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Oren et al. (WO2016092550A2 - hereinafter “Oren”).
Regarding claim 38, Oren teaches a method of manufacturing a human CTP-modified polypeptide of interest, the method comprising the steps of:
(a) stably transfecting a predetermined number of cells with an expression vector comprising a coding portion encoding said CTP-modified polypeptide of interest;
(i) wherein said transfected cells express and secrete said CTP- modified polypeptide of interest;
(b) obtaining cell clones that overexpress said CTP-modified polypeptide of interest;
(c) expanding said clones in solution to a predetermined scale;
(d) harvesting said solution containing said clones;
(e) filtering said solution containing said clones to obtain a clarified harvest solution; and,
(f) purifying said clarified harvest solution to obtain a purified protein solution having a desired concentration of a CTP-modified polypeptide of interest; thereby manufacturing the CTP-modified polypeptide of interest ([033, 035]; claim 1), wherein when said polypeptide of interest incudes an activated coagulation Factor VII (FVIIa) (claim 7; [035, 037]), wherein said CTP-modified polypeptide of interest polypeptide consists of three CTPs attached to the carboxy terminal of said polypeptide (claim 8; [089]). Oren teaches that the CTP-modified FVII polypeptide has the amino acid sequence of SEQ ID NO: 111 [0176, 0228, 0239], which is identical to the instant SEQ ID NO: 7. Oren teaches that the FVII-3CTP potency with an EC50 that translates to the instantly recited potency. Additionally, Oren teaches all the steps of the claimed invention, thus the CTP-modified FVII would have the recited properties. Further, whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited. MPEP 2111.04. Further, where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). “MPEP 2112.01.
Regarding claim 39, Oren teaches that the method of manufacturing CTP-modified polypeptide of interest comprises a step for obtaining clones that optimally express said CTP-modified polypeptide of interest from said WCB, and expanding said clones obtained from MCB ([0478, 0821]; claim 11).
Regarding claim 40, Oren teaches wherein said method of manufacturing is an animal-free process ([0821]; Claim 13).
Regarding claim 41, Oren teaches wherein the purity of the CTP-modified polypeptide of interest is at least 70% (claim 29, [0846]). Examiner notes that at least 70% includes higher than 70% which includes the instant percentages.
Regarding claim 42, Oren teaches that the clones express and secrete CTP-modified FVII at least 40 mg/L [0459, 0509].
Regarding claims 48-49, 54, Oren teaches that the method achieves at least a 20% recovery rate of highly glycosylated CTP-modified polypeptide of interest (claim 19; [0495]).
Regarding claim 50, Oren teaches the instant CTP-modified FVIIa. Oren teaches that the conjugate had improved potency, and CTP enhances the potency of proteins [028, 081, 0122, 0237]. Examiner notes that MPEP 2111.04 states: claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. In the instant case, the limitation expresses the intended result of the method step of claim 38 and would naturally flow.
Regarding claim 51, Oren teaches that the number of O-glycans per CTP is between 4-6 [0503-0505].
Regarding claim 56, Oren the cell clones are expanded in solution through a series of sub- cultivation steps up to production bioreactor level [0478].
Regarding claim 57, Oren teaches wherein said bioreactor comprises a disposable bioreactor, a stainless steel bioreactor, a fed-batch mode bioreactor, a batch mode bioreactor, a repeated batch mode bioreactor, or a perfusion mode bioreactor, or any combination thereof (claim 16; [0478]).
Regarding claim 58, Oren teaches purifying is accomplished by hollow fiber cassette or tangential flow cassette sequentially passing said clarified harvest solution through an anion exchange column and a hydrophobic interaction column, obtaining said clarified harvest obtained following step; and inactivating viruses present in said clarified harvest by incubating in a solution toxic to said viruses [0486], wherein the viruses are inactivated using a 1% Triton-X 100 solution [0490], and that the purification includes Ultrafiltration and Diafiltration [0831-0840].
Regarding claim 59, Oren teaches viral log reduction factor (LRF) of about 22 [0850].
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 43-46, 52-53, and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Oren et al. (WO2016092550A2 - hereinafter “Oren”), as applied to claim 38 above, and further in view of Chtourou et al. (US20090311239A1 – hereinafter “Chtourou”).
The teachings of Oren are disclosed above and incorporated herein by reference.
Oren does not teach that the percent N-glycan as recited in claim 43.
Chtourou teaches recombinant FVII wherein the FVII has defined glycan units (Title, Abstract). Chtourou teaches that the N-glycan moieties are at least 40% [0036, 0061]. Chtourou further teaches that FVII has a high sialic acid content such as at least 90% [0063-0064]. Examiner notes that this teaching would read on the limitation of high sialic acid content of at least 15 mol/mol. Chtourou further teaches that FVII contains carboxylated glutamic acid residues (Gla) at least 90% [0002, 0264-0269]. Chtourou teaches that the FVII recovery rate is at least 70% [0122, 0186] and a purity is higher than 90% [0125]. Chtourou teaches that the FVII exhibited a very reduced immunogenicity [0012].
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 FVII of Oren to include defined glycan units so as to have reduced immunogenicity. One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in preparing such a FVII since it has increased viral safety, exhibiting a very reduced immunogenicity.
Regarding claim 43, 45-46, Chtourou teaches recombinant FVII wherein the FVII has defined glycan units (Title, Abstract). Chtourou teaches that the N-glycan moieties are at least 40% [0036, 0061].
Regarding claim 44, Chtourou further teaches that FVII has a high sialic acid content such as at least 90% [0063-0064]. Examiner notes that this teaching would read on the limitation of high sialic acid content of at least 15 mol/mol.
Regarding claims 52-53, Oren teaches the CTP-modified polypeptide of interest having a high glycosylation content and a high percentage of glycosylation sites glycosylated [0458, 0502, 0827, 0842].
Regarding claim 55, Oren teaches FVII is cleaved at R152 resulting in heavy and light chain domains that are held together by a single disulfide bridge [0743] and further teaches the sequence of SEQ ID NO: 34 which is identical to the instant SEQ ID NO: 7.
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.
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, 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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MERCY H SABILA/Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
Prosecution Insights