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 .
DETAILED ACTION
Preliminary Amendment
1. Applicant's preliminary amendment filed 7/6/2026 is acknowledged and has been entered. Claim 1 has been amended. Claims 6-36 have been cancelled. Accordingly, the species election is moot. Claims 1-5 are pending and are under examination.
Priority
2. Receipt is acknowledged of certified copies of foreign priority papers required by 37 CFR 1.55, which papers have been placed of record in the file.
3. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d) or (f), 365(a) or (b) or 386(a). Based on the filing receipt, the effective filing date of this National Stage application, which is a 371 of PCT/JP2022/009851 filed 03/08/2022, is March 9, 2021 which is the filing date of Foreign Application JAPAN 2021-037528 filed 03/09/2021 from which the benefit of foreign priority is claimed.
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.
4. Claims 3-5 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 3 has improper antecedent basis problem in reciting “a CH1 region of a heavy chain of the antibody.” Perhaps, Applicant intends “a CH1 region of the heavy chain of the antibody” having been recited in claim 1.
Claim 4 is indefinite in reciting “a strong anion exchanger” because “strong” is a subjective term lacking a comparative basis for defining its metes and bounds.
Claim 5 is also indefinite in reciting “a weak cation exchanger” because “weak” is a subjective term lacking a comparative basis for defining its metes and bounds.
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.
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.
5. Claims 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Sonoda et al. (US 2019/0338043 A1) in view of Koshimura et al. (US 2019/0225700 A1).
Sonoda et al. disclose a method for producing a fusion protein in which an antibody and a human lysosomal enzyme are fused to form the fusion (recombinant) protein which comprises humanized anti-human transferrin receptor (anti-hTfR) Fab antibody and human α-L-iduronidase (hIDUA) [0516, 0520, 0521]. The method comprises: (a) culturing mammalian cells that produce the fusion protein in a serum-free medium to secrete the fusion protein in a culture medium; (b) collecting a culture supernatant by removing the mammalian cells from the culture medium; and, (c) purifying the fusion protein from the culture supernatant using column chromatography; wherein the column chromatography comprises: a column chromatography having a solid phase material (CaptureSelect column) to which a substance having affinity for the antibody (CH1 affinity column) is bound (Example 33). The human lysosomal enzyme is hIDUA and the antibody is an Fab having a light chain comprising SEQ ID NO:22 (SEQ ID No. 23); wherein the anti-hTfR Fab is bound to hlDUA via amino acids consonant to SEQ ID No. 4 as set forth in claim 1, on the C terminal side such that the fusion protein forms amino acid SEQ ID No. 93 which is consonant to SEQ ID No. 27 as recited in claim 1 [0516, 0520, 0521].
Although silent in teaching that “the heavy chain is bound to the human α-L-iduronidase via SEQ ID NO:4 on the C-terminal side;” Sonoda et al. indeed show forming the resultant fusion protein having the amino acid SEQ ID NO: 93 which is consonant to the fusion protein formed having amino acid SEQ ID NO: 27 as recited in Applicant’s claimed invention.
Sonoda et al. differ from the instant invention in failing to teach further performing anion exchange column chromatography, cation exchange column chromatography, and size exclusion column chromatography in this order.
Koshimura et al. teach a method of producing a fusion protein in which human anti-hTfR antibody and a human lysosomal enzyme are fused; wherein the human lysosomal enzyme is human α-L-iduronidase (Abstract; [0042], [0100], [0101]). The method comprises: (a) culturing mammalian cells that produce the fusion protein in a serum-free medium to secrete the fusion protein in a culture medium; (b) collecting a culture supernatant by removing the mammalian cells from the culture medium; and, (c) purifying the fusion protein from the culture supernatant using column chromatography; wherein the column chromatography comprises: column chromatography having a solid phase material to which a substance having affinity for the antibody is bound (CH1 affinity chromatography) and size exclusion column chromatography (Abstract; [0012-0016, 0160, 0163, 0171-0175]). Koshimura et al. teach that the human lysosomal enzyme is linked to the antibody heavy chain on the C terminal side [0030, 0112]. In paragraph [0003], Koshimura et al. state that both of anion exchange column chromatography with strong anion exchanger and cation exchange column chromatography with weak cation exchanger have been used conventionally in the art in purifying lysosomal enzymes expressed as recombinant fusion proteins to such levels as permitted for use as medical drugs.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to incorporate the method of Koshimura in purifying recombinant anti-hTfR fused to human lysosomal enzymes including anti-hTfR Fab fused to hIDUA as taught by Sonoda secreted from cultured mammalian cells using CH1 affinity column chromatography and size exclusion chromatography with the suggestion that anion exchange column chromatography in addition to CH1 affinity column chromatography and cation exchange column chromatography in addition to CH1 affinity column chromatography have also been conventionally used in purifying recombinant proteins including anti-hTfR fused to human lysosomal enzymes to such level as permits its use as medical drug [0003], into the method of Sonoda that produces the fusion protein having anti-hTfR Fab fused to hIDUA purified by CH1 affinity column chromatography for use as medical drug capable of penetrating blood-brain barrier because Koshimura taught that CH1 affinity chromatography and size exclusion chromatography, alongside anion exchange column chromatography and cation exchange column chromatography in addition to CH1 affinity chromatography have been selectively used to purify recombinant protein secreted from cells including fusion proteins having Fab antibody fused to human lysosomal enzymes such as the anti-hTfR Fab fused to hIDUA produced by Sonoda. One of ordinary skill would have been motivated to incorporate the teachings of Koshimura into the method of producing recombinant anti-hTfR Fab fused to hIDUA fusion protein having SEQ ID No. 27 as taught by Sonoda because Koshimura taught that use of combination purification methods provides advantage in producing purified recombinant proteins capable of removing contaminants in a level that permits use in medical drug applications.
With respect to the recitation “wherein the column chromatography using the material to which the substance having affinity for the antibody is bound as a solid phase, the anion exchange column chromatography, the cation exchange column chromatography, and the size exclusion column chromatography are used in this order” in claim 2, the examiner recognizes that the test for combining references is what the combination of disclosures, taken as a whole, would suggest to one of ordinary skill in the art. See: In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); or, In re McLaughlin, 170 USPQ 209 (CCPA 1971); or, KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). References are evaluated by what they suggest to one versed in the art, rather than by their specific disclosures. See: In re Bozek, 163 USPQ 545 (CCPA 1969). A person of ordinary skill in the art, using common knowledge and common sense, is also a person of ordinary creativity capable of fitting the multiple teachings of the combination of references together like pieces of a puzzle, in consideration of the goals intended to be achieved and specific problem being addressed by the individual references. In the case of Applicant’s invention as well as the combination of references; the goal of each of the methods is optimization with ample motivation to achieve utmost purity levels of recombinant proteins secreted by mammalian cells, specifically anti-hTfR fused to human lysosomal enzymes for use as medical grade drugs. There is no requirement that the claimed invention or a motivation to make the modification be expressly articulated in any one or all of the references. Any need or problem known at the effective filing date of the instant invention can provide a reason for combining elements and combinations of conventionally used method steps of the different references. Accordingly, it would also have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to combine conventionally known purification techniques and rearrange the order of purification steps because it has been held that merely reversing the order of steps in a multi-step process in not a patentable modification absent unexpected or unobvious results, Ex parte Rubin, 128 U.S.P.Q. 440 (P.O.B.A. 1959). Cohn v. Comr. Patents, 251 F. Supp. 437, 148 U.S.P.Q. 486 (D.C. 1966).
6. No claims are allowed.
Remarks
7. Prior art made of record are not relied upon but considered pertinent to the applicants' disclosure:
Fahrner et al. (Industrial Purification of Pharmaceutical Antibodies: Development, Operation, and Validation of Chromatography Processes. Biotechnology and Genetic Engineering Reviews 18: 301-327 (2001) IDS) provide reviews of protein antibody recovery and purity using different chromatography techniques including protein A affinity chromatography, cation exchange chromatography, and anion exchange chromatography.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GAILENE R. GABEL whose telephone number is (571)272-0820. The examiner can normally be reached Monday, Tuesday, and Thursday 5:30 AM to 4:00 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, Gregory S. Emch can be reached at (571) 272-8149. 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.
/GAILENE GABEL/Primary Examiner, Art Unit 1678
September 3, 2026
Prosecution Insights