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
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on September 19, 2025 has been entered.
Amendment Entry
2. Applicant's amendment/response filed August 27, 2025 is acknowledged and has been entered. Claims 1 and 6 have been amended. Claims 27-29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Accordingly, claims 1-9, 12, and 21-29 are pending. Claims 1-9, 12, and 21-26 are under examination.
Withdrawn Rejections / Objections
3. Any objection or rejection not reiterated herein, has been withdrawn.
4. In light of Applicant’s amendment and arguments, the rejection of claims 1-9, 12, and 21-26 on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,649,449 in view of CHO et al. (J Biomed Sci. Vol. 9: 631-638 (2002)), is hereby, withdrawn.
5. In light of Applicant’s amendment and arguments, the rejection of claims 1-9, 12, and 21-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 10,329,594 in view of CHO et al. (J Biomed Sci. Vol. 9: 631-638 (2002)), is hereby, withdrawn.
Priority
6. Applicant’s submission of an updated and corrected application data sheet (ADS) filed May 23, 2024 is acknowledged. Based on the ADS, Applicant has withdrawn the priority claim of this application to ASN 15/254,852 filed 9/1/2016, now U.S. Patent No. 10,329,594 and provisional application 62/213,880 filed 9/3/2015.
As such, Applicant’s updated claim for the benefit of 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. The application is a continuation of ASN 16/440,776 filed 6/13/2019 which is a continuation of PCT/US2019/036379 filed 6/10/2019. Accordingly, the effective filing date of the instant application is June 10, 2019 which is the filing date of PCT/US2019/036379 from which the benefit of priority is claimed.
Applicant is advised to request a corrected Filing Receipt that reflects the updated ADS to the Office of Patent Application Processing (OPAP).
Claim Rejections - 35 USC § 102
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.
7. Claims 1, 3-8, 12, and 21-25 are rejected under 35 U.S.C. 102(a) as being anticipated by CHO et al. (Establishment of a Human Somatic Hybrid Cell Line for Recombinant Protein Production. J Biomed Sci. Vol. 9: 631-638 (2002)).
Cho et al. provide that cell fusion techniques have been used to derive mammalian host cell lines suitable for large scale production of therapeutic proteins (Abstract). In this study, Cho et al. focused on developing cell lines with human glycosylation profiles capable of secreting high levels of therapeutic proteins (p. 632, left col., 1st full ¶).
Cho et al. teach a method of obtaining a hybrid cell line adapted for industrial production by fusing human embryonic kidney 293 cell line (HEK 293 cells) with human suspension B cells (primary cell population) (p. 632, left col., 1st full ¶). The method comprises: providing a starting mixture of eukaryotic (mammalian) cells. In this case, Cho et al. teach using a starting mixture of HEK 293 cells or cell line and Burkitt’s lymphoma 2B8: HH514-16 cell line (Abstract; p. 632, left col., 1st & 2nd full ¶s). The method further comprises treating the starting mixture of cells with polyethylene glycol (PEG) fusogenic agent and culturing the PEG-treated HEK 293 cells and 2B8 cells in a culture medium supplemented with hypoxanthine-aminopterin-thymidine and G41B, so as to form one or more hybrid HKB cells (HKB hybrid clones: hybrid of kidney and B cells) and so as to eliminate non-fused cells (Abstract; p. 632, left col., 1st to right col. 2nd full ¶). Cho et al. further teach selecting for cells endowed with human glycosylation machinery and growth properties (HKB11 hybrid cells: better growth rate parameters relative to the other HKB hybrid cells). Cho et al. specifically established the HKB11 hybrid cell line (HKB11 clone) shown to be endowed with strong growth properties (grows readily including in serum free medium) and human glycosylation machinery which involves both endoplasmic reticulum (ER) and Golgi apparatus (GA); hence, relatively high density of ER per hybrid cell and/or relatively high density of GA per hybrid cell which is crucial for protein production compared with other hybrid cells formed (p. 632, left col. 1st full ¶ to right col. 2nd full ¶; p. 633, left col. last full ¶ to right col.). The HKB11 hybrid cells are specifically shown to support high-level production of proteins including cytokines, IL-2, IL-4, ICAM-1, rFVIII (Abstract). Cho et al. specifically taught that the HKB11 hybrid cells show production or secretion levels of ICAM-1 and IgG at approximately 10 times higher than the starting mixture cell population, and 6 times higher secretion levels of other proteins (p. 633, right col. last ¶ to p. 634).
Cho et al. teach performing successive dilution culture (dilution cloning) of the hybrid cells formed (p. 632, left col. 3rd ¶ to right col. 1st full ¶). Cho et al. teach fusing the two cell lines in the starting mixture to form hybrid cells using PEG fusion (fusogenic agent) and centrifugation (Abstract; p. 632, left col. 1st ¶ to right col. 1st full ¶). Cho et al. teach using and comparing HEK 293 cells and CHO cells (Abstract; p. 631, right col.). Cho et al. also teach transfecting starting mixtures of CHO cells, HEK 293 cells, and 2B8 cells, as well as the hybrid cell line HKB11 cell line with transgene or expression vectors pSM98, pSH125, and pCISF8 that each encodes a gene product or marker protein ICAM, anti-TNF, and recombinant FVIII, respectively. The gene products are intended for use as a pharmaceutical agent (human therapeutic proteins) (Abstract; p. 631, right col., p. 632, right col. 3rd full ¶; p. 633, right col. to p. 634; Figure 3). Cho et al. teach replacing the transgene with a different transgene encoding a gene product (various recombinant proteins: activated protein C, recombinant adenovirus; rFVIII) for commercial production (p. 631, right col.; p. 633, right col. to p. 634). Cho et al. teach optically detecting ICAM-1 and rFVIII using ELISA or chromogenic detection (p. 632, right col. 4th full ¶ to p. 633, left col 3rd full ¶).
With respect to the recitation of “selecting and recovering cells that proliferate more rapidly,” Applicant’s disclosure in the abstract and paragraphs [0034, 0077, 0079] appear to provide that cell growth and cell proliferation are intended to be consonant and synonymous to each other. Accordingly, the teaching of Cho that selects for “human glycosylation machinery and growth properties” in page 632, first paragraph appears to read on Applicant’s claimed invention.
It is proper for purposes of this anticipation rejection to interpret "proliferation" in claim 1 as cell growth in the teaching of Cho because of reasons as set forth supra and because unpatented claims are given the broadest reasonable interpretation consistent with the specification.
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.
8. Claims 9 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over
CHO et al. (J Biomed Sci. Vol. 9: 631-638 (2002)) in view of Terasaki et al. (Fluorescent Staining of Subcellular Organelles: ER, Golgi Complex, and Mitochondria. Current Protocols in Cell Biology Unit 4.4 pp. 1-18 (1998)).
Cho et al. is discussed supra. Cho et al. differ from the instant invention in failing to teach that the transfected hybrid cell line produces at least eight grams of the gene product per liter of culture medium. Cho et al. further does not teach incubating the hybrid cells with a vital dye that stains ER and/or GA for sorting according to the amount of the vital dye associated with each hybrid cell.
Terasaki et al. teach staining endoplasmic reticulum (ER) and/or Golgi apparatus (GA) in cells using vital dyes including fluorescent dye DiOC6(3) and fluorescent ceramide analogs including C6-NBD-Cer and BODIPY-Cer). Terasaki et al. teach that fluorescent dye DiOC6(3) is a particularly advantageous vital dye for staining ER because it allows ER to be specifically distinguished from other organelles. Terasaki et al. further teach that fluorescent ceramide analogs C6-NBD-Cer and BODIPY-Cer) are advantageous vital stains for GA because they readily accumulate in the Golgi complex which receives, processes, and sorts newly synthesized proteins exported from the ER (p. 4.4.1, 1st to 3rd full ¶s).
It would have been obvious to one or ordinary skill in the art at the time the invention was filed to have stained the hybrid cells of Cho using the ER vital stain and GA vital stain taught by Terasaki because Terasaki taught that an ability to specifically stain, distinguish, and identify different subcellular compartments and organelles is crucial for understanding cell function and protein synthesis such as in the method of Cho. One would have been motivated to incorporate the vital stains taught by Terasaki for application into the method of establishing human somatic hybrid cell line as taught by Cho because Cho identified and established HKB11 hybrid cell line endowed with human glycosylation machinery and growth properties, which the vital stain taught by Terasaki can enable staining of the HKB11 hybrid cell line’s ER and/GA which are responsible for manifesting the 10 times higher increased production or secretion levels of ICAM-1 and IgG, and 6 times higher secretion levels of other proteins.
With respect to claim 26 which recites “the transfected cell population produces at least eight grams of the gene product per liter of culture medium”, it is deemed that "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation";
Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art."). Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). Since Cho et al. teach distinguishably measuring 6 times and 10 times protein production or secretion by HKB11 hybrid cells relative to other hybrid clones and/or the starting mixture; absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable range of the method disclosed by the prior art by normal optimization procedures.
Response to Arguments
9. Applicant's arguments filed August 27, 2025 have been fully considered but they are not persuasive.
A) Applicant argues that the claims are not anticipated by Cho because Cho did not set out to increase protein production by making a cell line that proliferates fast. Applicant specifically contends that protein proliferation does not depend on proliferation rate of the cells making the protein.
Applicant’s argument is not persuasive because claim 1 does not appear to recite obtaining and making a cell line set out to increase protein production. In fact, the preamble of claim 1 recites “obtaining a hybrid cell line adapted for industrial production” but fails to clearly define that “industrial production” intends “increased protein production.” Additionally, steps a) to d) recite steps of forming hybrid cells and selecting and recovering hybrid cells that proliferate more rapidly; whereas nowhere in claim 1 appears to intend for the selected and recovered hybrid cells that proliferate rapidly to further encompass hybrid cells capable of increased protein production.
B) Applicant further argues that Cho does not teach or suggest selecting cells for higher rate of proliferation and that Cho also does not teach the type of dilution culture referred to in Applicant’s invention so as to select fast growing cells from slower growing cells.
Applicant’s argument is not persuasive because as set forth herein supra, Cho teaches selecting for cells endowed with human glycosylation machinery and growth properties in page 632, first full paragraph, which appears to encompass cell proliferation, as claimed, and as further supported in Applicant’s disclosure. As to the type of successive dilution culture referred to in Applicant’s disclosure being distinct from the teaching of Cho; it is deemed that paragraph [0050] of the specification and reiterated in page 8 of Applicant’s response, is not recited in claim 5. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Allowable Subject Matter
10. Claim 2 is free of the prior art of record. Claim 2 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
11. No claims are allowed.
THIS ACTION IS MADE FINAL. 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.
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
October 18, 2025