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 .
Applicant’s amendment and response filed on 5/20/2026 has been received and entered into the case.
Claim 7 has been canceled, and claims 1-6 and 8-13 have been considered on the merits. All arguments have been considered.
Response to Amendment
The claim rejection under 35 USC 112(b) has been withdrawn due to the instant amendment.
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.
Claim(s) 1-6 and 8-13 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Huang et al. (US 948190 B2; IDS ref.)
Regarding claims 1-2, 5, Huang et al. teach a method comprising culturing mammalian cells expressing a recombinant protein including antibody in a bioreactor and the culture medium contains at least 3, 6, 9 g/L mannose (col. 2, lines 1-17; col. 3, lines 15-20). Regarding the intended outcome disclosed in the preamble of claim 1, the limitation does not provide any active step to be carried out, and rather it is directed to the result of the claimed steps. As Huang et al. teach the identical steps as claimed, the identical results are expected.
Regarding claim 3, Huang et al. teach that the bioreactor has a capacity of at least 500 L (col. 3, lines 11-12).
Regarding claim 4, Huang et al. teach the antibody as a recombinant protein and the antibody includes monoclonal antibody (col. 13, lines 40-44) and exemplify various known mAb such as adalimumab, bevacizumab, etc. (col. 14, lines 29-42). These “mabs” are monoclonal IgGs.
Regarding the increase by at least 2% (claim 1) or at least 2.5% (claim 6), the wherein clause of these claims is directed to the results of the claimed method but does not require any active step to be performed. Thus, the limitation of the wherein clause does not provide any patentable weight in determining patentability of the claimed method. Furthermore, the same results are expected from the method of Huang et al. as they teach the identical method steps as the claimed method.
Regarding claim 8 directed to the fed-batch process, Huang et al. teach that the mammalian cells inoculated into the production bioreactor can be maintained as a batch culture using a fed-batch process (col. 7, lines 5-9).
Regarding claim 9 directed to the perfusion process, Huang et al. teach that for cultures maintained by perfusion, perfusion feeds can begin at any time, for example, perfusion feeds can begin on or about day 3 or 4 of the culture or a day or two earlier or later (col. 7, lines 16-19).
Regarding claim 10 directed to the method further comprising isolating step of the expressed antibody, Huang et al. teach a method further comprising a step of harvesting and purifying the recombinant protein produced by the cell culture (col. 22, claim 14).
Regarding claim 11, the method of claim 11 is interpreted the same as claim 1 because the active steps of claim 11 are identical to those of claim 1 because the intended purpose of the method to match the afucosylation of a recombinantly produced antibody to a previously obtained target afucosylation percentage for the same antibody does not provide any additional method steps to the steps of claim 1. Furthermore, the “previously obtained target afucosylation percentage for the same antibody” does not provide any standard and thus, the target afucosylation percentage is considered as any afucosylation percentage, and thus, the teachings of Huang et al. as discussed with regard to claim 1 would anticipate the subject matter of claim 11.
Regarding claim 12, the wherein clause of the claim is directed to the result obtainable , and it does not limit the steps for the claimed method. Thus, claim 12 is interpreted the same as claim 11. Huang et al. teach the method steps disclosed in claim 11 as discussed above.
Regarding claim 13 directed to the perfusion process, Huang et al. teach that for cultures maintained by perfusion, perfusion feeds can begin at any time, for example, perfusion feeds can begin on or about day 3 or 4 of the culture or a day or two earlier or later (col. 7, lines 16-19).
Thus, the reference anticipates the claimed invention.
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.
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.
Claim(s) 1-6 and 8-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Huang et al. (supra).
Regarding claims 1-2 and 5, Huang et al. teach a method comprising culturing mammalian cells expressing a recombinant protein including antibody in a bioreactor and the culture medium contains at least 3, 6, 9 g/L mannose (col. 2, lines 1-17; col. 3, lines 15-20). Regarding the intended outcome disclosed in the preamble of claim 1, the limitation does not provide any active step to be carried out, and rather it is directed to the result of the claimed steps. As Huang et al. teach the identical steps as claimed, the identical results are expected.
Regarding claim 3, Huang et al. teach that the bioreactor has a capacity of at least 500 L (col. 3, lines 11-12).
Regarding claim 4, Huang et al. teach the antibody as a recombinant protein and the antibody includes monoclonal antibody (col. 13, lines 40-44) and exemplify various known mAb such as adalimumab, bevacizumab, etc. (col. 14, lines 29-42). These “mabs” are monoclonal IgGs. Thus, it would have been obvious to a person skilled in the art to use the method of Huang et al. for producing monoclonal IgG with a reasonable expectation of success.
Regarding the increase by at least 2% (claim 1) or at least 2.5% (claim 6), the wherein clause of these claims is directed to the results of the claimed method but does not require any active step to be performed. Thus, the limitation of the wherein clause does not provide any patentable weight in determining patentability of the claimed method. Furthermore, the same results are expected from the method of Huang et al. as they teach the identical method steps as the claimed method.
Regarding claim 8 directed to the fed-batch process, Huang et al. teach that the mammalian cells inoculated into the production bioreactor can be maintained as a batch culture using a fed-batch process (col. 7, lines 5-9). Thus, it would have been obvious to a person skilled in the art to use the fed-batch process in order to produce a recombinant antibody using the method of Huang et al. with a reasonable expectation of success.
Regarding claim 9 directed to the perfusion process, Huang et al. teach that for cultures maintained by perfusion, perfusion feeds can begin at any time, for example, perfusion feeds can begin on or about day 3 or 4 of the culture or a day or two earlier or later (col. 7, lines 16-19). Thus, it would have been obvious to a person skilled in the art to use the perfusion process in order to produce a recombinant antibody using the method of Huang et al. with a reasonable expectation of success.
Regarding claim 10 directed to the method further comprising isolating step of the expressed antibody, Huang et al. teach a method further comprising a step of harvesting and purifying the recombinant protein produced by the cell culture (col. 22, claim 14). Thus, it would have been obvious to a person skilled in the art to harvest, isolate and purify the produced recombinant antibody using the method of Huang et al. in order to utilize the antibody for subsequent analysis and/or therapeutic application with a reasonable expectation of success.
Regarding claim 11, the method of claim 11 is interpreted the same as claim 1 because the active steps of claim 11 are identical to those of claim 1 because the intended purpose of the method to match the afucosylation of a recombinantly produced antibody to a previously obtained target afucosylation percentage for the same antibody does not provide any additional method steps to the steps of claim 1. Furthermore, the “previously obtained target afucosylation percentage for the same antibody” does not provide any standard and thus, the target afucosylation percentage is considered as any afucosylation percentage, and thus, the teachings of Huang et al. as discussed with regard to claim 1 would anticipate the subject matter of claim 11.
Regarding claim 12, the wherein clause of the claim is directed to the result obtainable , and it does not limit the steps for the claimed method. Thus, claim 12 is interpreted the same as claim 11. Huang et al. teach the method steps disclosed in claim 11 as discussed above.
Regarding claim 13 directed to the perfusion process, Huang et al. teach that for cultures maintained by perfusion, perfusion feeds can begin at any time, for example, perfusion feeds can begin on or about day 3 or 4 of the culture or a day or two earlier or later (col. 7, lines 16-19).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Arguments
Regarding claim rejection under 112(b), applicant’s arguments with respect to the instant amendment have been fully considered and are persuasive. The claim rejection under 112(b) has been withdrawn.
Regarding the 102 and 103 rejection based on Huang et al., applicant argued that the Huang reference fails to disclose that the addition of mannose increases the afucosylation of the antibody by at least 2% (claim 1) or 2.5% (claim 6).
As discussed in the claim rejections, it is the examiner’s position that the limitations are directed to the results of the claimed method steps. As the claim rejection clearly showed that Huang teaches the identical steps of culturing cells expressing an antibody in a bioreactor, and adding mannose to the cell culture during the antibody production as the claimed method, thus, the same results are expected.
The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) and In re Tomlinson, 363 F.2d 928, 150 USPQ 623 (CCPA 1966). See M.P.E.P. § 2112.02.
Applicant asserted that “by at least 2%” is a specific measurable limitation and can be achieved by the claimed method. This is clear acknowledgement by applicant that the limitation is a result of the claimed method.
Applicant further stated that the limitation is not merely a result that can be expected by the method of Huang. The examiner respectfully disagrees with this allegation. The claims disclose the active steps to be carried out to achieve the claimed results, and the claims only disclose the steps of culturing the cells expressing antibody and adding mannose during the antibody production process. There is no other critical parameter or condition required to achieve the claimed results. Thus, any teaching that meets the claimed steps and materials are expected to produce the same results as claimed.
To invalidate a patent by anticipation, a prior art reference normally needs to disclose each and every limitation of the claim. See Standard Havens Prods., Inc. v. Gencor Indus., Inc., 953 F.2d 1360, 1369, 21 USPQ2d 1321, 1328 (Fed. Cir. 1991). However, a prior art reference may anticipate when the claim limitation or limitations not expressly found in that reference are nonetheless inherent in it. See id. and Verdegaal Bros., Inc. v. Union Oil Co. of Cal., 814 F.2d 628, 630, 2 USPQ2d 1051,1053 (Fed. Cir. 1987). Under the principles of inherency, if the prior art necessarily functions in accordance with, or includes, the claimed limitations, it anticipates. See In re King, 801 F.2d 1324, 1326, 231 USPQ 136, 138 (Fed. Cir. 1986). Inherency is not necessarily coterminous with the knowledge of those of ordinary skill in the art. See Titanium Metals, 778 F.2d at 780. Artisans of ordinary skill may not recognize the inherent characteristics or functioning of the prior art. See id. at 782. However, the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer. See id. at 782 ("Congress has not seen fit to permit the patenting of an old [composition], known to others…, by one who has discovered its…useful properties."); Verdegaal Bros., 814 F.2d at 633.
This court's decision in Titanium Metals illustrates these principles. See Titanium Metals, 778 F.2d at 775. In Titanium Metals, the patent applicants sought a patent for a titanium alloy containing various ranges of nickel, molybdenum, iron, and titanium. The claims also required that the alloy be "characterized by good corrosion resistance in hot brine environments." Titanium Metals, 778 F.2d at 776. A prior art reference disclosed a titanium alloy falling within the claimed ranges, but did not disclose any corrosion-resistant properties. This court affirmed a decision of the PTO Board of Appeals finding the claimed invention unpatentable as anticipated. This court concluded that the claimed alloy was not novel, noting, "it is immaterial, on the issue of their novelty, what inherent properties the alloys have or whether these applicants discovered certain inherent properties." Id. at 782. This same reasoning holds true when it is not a property, but an ingredient, which is inherently contained in the prior art. The public remains free to make, use, or sell prior art compositions or processes, regardless of whether or not they understand their complete makeup or the underlying scientific principles which allow them to operate. The doctrine of anticipation by inherency, among other doctrines, enforces that basic principle." See Atlas Powder Co. v. IRECO Inc., 51 USPQ2d 1943 (Fed. Cir. 1999).
Thus, a reference may be anticipatory if it discloses every limitation of the claimed invention either explicitly or inherently. A reference includes an inherent characteristic if that characteristic is the natural result flowing from the reference’s explicitly explicated limitations. Continental Can Co. USA, Inc. v. Monsanto Co., 948 F.2d 1264, 1269, 20 USPQ2d 1746, 1749 (Fed. Cir. 1991).
Applicant argued that Example 3 of Huang showed afucosylation less than 2% higher in the mannose supplemented group compared to those without mannose (untreated) group. The examiner disagrees with this analysis. The table showing the results of Example 3 of Huang disclose 3.8% when no mannose added and 4.8% with mannose added at a M/H ratio of 0.5. The difference of 3.8% to 4.8% is 26.3% increase [(4.8-3.8)/3.8 x 100] which is far greater than 2% increase.
It is noted that applicant appears to interpret or intends to claim such that the limitation of “by at least 2%” being meant to be a 2% “percentage-point” increase of the percentage of afucosylation in the presence of mannose compared to the absence of mannose. However, the limitation of “increased by at least 2%” in the claim is not disclosed as “percentage point increase”, and thus, the instant limitation should be interpreted as a relative increase between two percentages not the percentage-point increase. Thus, the teaching of Huang resulting in 26.3% increase (Example 3) would meet the limitation of at least 2% or 2.5% increase.
It is noted that even if the claims are amended to clarify that the increase is based on percentage point without introducing new matter, the data shown in Table 2 of the instant specification fails to support the limitations directed to the “at least 2%” or “at least 2.5%” as claimed. This is because Table 2 shows the control is 5.21% of afucosylation and only 6g/L of mannose addition was able to meet “2% point increase” (i.e. 5.21% to 7.27%). There is no support for “at least 2%” or “at least 2.5%” as these limitations are open-ended without upper limitation.
Applicant asserted that the culture conditions in the presence application do not include hexose. It is acknowledged that the instant specification is silent on hexose. The instant specification however discloses that “In some cases, the one or more input components (also referred to as one or more input materials) may include one or more nutrients, such as glucose, vitamins, lipids, mannose, etc.” (para. 42). Although it is not clear what the source of sugar in the culture medium is, however, a typical mammalian cell culture medium contains glucose, and the specification mentions the use of glucose, which is hexose, it appears that the control cell culture medium in Table 2 of the instant specification would contain glucose. Furthermore, applicant’s argument is directed to the feature that is not claimed as the instant claims do not exclude the use of hexose in the culture medium along with mannose. Thus, applicant’s argument is not persuasive to overcome the claim rejection based on Huang.
Conclusion
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 TAEYOON KIM whose telephone number is (571)272-9041. The examiner can normally be reached 9-5 EST Monday-Friday.
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, JAMES SCHULTZ can be reached at 571-272-0763. 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.
/TAEYOON KIM/Primary Examiner, Art Unit 1631
Prosecution Insights