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 .
The amendment filed 11/28/25 has been entered. Claims 20-22 have been cancelled. Claims 1-19 and 23 are pending.
Claim Rejections Withdrawn
The rejection of claims 1-19 and 23 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in view of the amendment to the claims.
The rejection of claim 8-9 and 14-15 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph is withdrawn in view of the amendment to the claims.
The rejection of claim(s) 1-2, 8-9, 14-15, 17-19 and 23 under 35 U.S.C. 102(a)(1)) as anticipated by Allison et al. US20060165702, July 2006 is withdrawn in view of the amendment to the claims.
The rejection of claim(s) 1 and 10 under 35 U.S.C. 103 as being unpatentable over Allison et al. US20060165702, July 2006 in view of Yamane-Ohnuki et al. Biotechnol Bioeng, 2004 Sept 5: 87(5):614-22 is withdrawn in view of the amendment to the claims.
New Claim Rejections
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 3-19 and 23 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.
The claims recite percentage of glycoforms in an antibody. E.g. “wherein the antibody comprises no less than 60% G0 glycoform”. This is confusing because in the specification in example 5 table 4 the partial glycoform percentage content is listed for a composition of antibodies i.e. an antibody sample. In paragraph 163, the partial glycoform percentage content of a group of BAT0303F antibodies is set forth, wherein the content of G0 glycoform in the group of antibodies is no less than 60%.
As claimed the antibody itself comprises a percentage of glycoforms. The antibody art teaches that there are different glycoforms of antibodies dictated by the glycan structure attached to the Fc region. See different antibody glycoforms and their unique glycan structure1.
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Thus, in an antibody preparation there can be different amounts of glycoforms of the same antibody as evidenced by table 4 of the specification. Thus, the antibody comprising a percentage of glycoforms does not make sense as each antibody is a glycoform itself, but there can be different percentages of antibody glycoforms in an antibody preparation.
Regarding claim 11, the metes and bounds of “wherein the content of a main peak in the antibody composition is at least 72%”. What is a peak of an antibody composition? It is not clear what this peak is referring to.
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) 1-2 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Luo et al. Glycoengineering of pertuzumab and its impact on the pharmacokinetic/pharmacodynamic properties. Sci Rep. 2017 Apr 11;7:46347. doi: 10.1038/srep46347 as evidenced by Allison et al. US20060165702, July 2006 cited previously.
Luo et al disclose an antibody specifically binding to HER2 i.e. pertuzumab, wherein the pertuzumab is expressed by CHO cells with the FUT8 gene knocked out. Luo et al disclose a composition/pharmaceutical composition comprising phosphate buffered saline and pertuzumab wherein the pertuzumab has been purified from said CHO cells with the FUT8 gene knocked out. See p. 7 under preparation of glycoengineered pertuzumab and page 2 under characterization of pertuzumab expressed in Glycoengineered CHO cells.
As evidenced by Allison pertuzumab comprises the heavy chain sequence SEQ ID NO: 9 (see appendix A for alignment of the heavy chain SEQ ID NO: 14 of pertuzumab and SEQ ID NO: 9 of this application) and comprises the light chain sequence set forth in SEQ IDNO: 10 ( see alignment in appendix B for the light chain SEQ ID NO: 13 of pertuzumab and SEQ ID NO: 10 of this application).
Thus, said heavy chain sequence of pertuzumab comprise a HCDR1 comprising the sequence set forth in SEQ ID NO: 1 (b) an HCDR2 comprising the sequence set forth in SEQ ID NO: 2, (c) an HCDR2 comprising the sequence set forth in SEQ ID NO: 3; and the light chain sequence comprises:
(d) a LCDR1 comprising the sequence set forth in SEQ ID NO: 4, (b) an LCDR2 comprising the sequence set forth in SEQ ID NO: 5, (c) an LCDR2 comprising the sequence set forth in SEQ ID NO: 6.
Claim 1:Luo et al disclose the same antibody as claimed comprising the CDRs as set forth above expressed by CHO cell with the gene FUT8 knocked out, therefore said antibody will also have a fucosylation level of 0-5%.
Claim 2: Luo et al disclose the same antibody as claimed comprising the CDRs as set forth above expressed by CHO cell with the gene FUT8 knocked out, therefore said antibody will also have a fucosylation level of 0%. Moreover, Luo et al disclose the antibody is nonfucosylated. See abstract, p. 2 under “characterization of pertuzumab expressed in Glycoengineered CHO cells.
Claim(s) 3-5, 8-9, 11-15, 17, 18, 19 and 23 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gennaro et al.US 2014/0308277 10/16/2014 as evidenced by Allison et al. US20060165702, July 2006 cited previously.
Gennaro et al discloses an antibody pertuzumab specifically binding to HER2 that comprises comprise a HCDR1 comprising the sequence set forth in SEQ ID NO: 1 (b) an HCDR2 comprising the sequence set forth in SEQ ID NO: 2, (c) an HCDR2 comprising the sequence set forth in SEQ ID NO: 3; and the light chain sequence comprises:
(d) a LCDR1 comprising the sequence set forth in SEQ ID NO: 4, (b) an LCDR2 comprising the sequence set forth in SEQ ID NO: 5, (c) an LCDR2 comprising the sequence set forth in SEQ ID NO: 6.
As evidenced by Allison pertuzumab comprises the heavy chain sequence SEQ ID NO: 9 (see appendix A for alignment of the heavy chain SEQ ID NO: 14 of pertuzumab and SEQ ID NO: 9 of this application) and comprises the light chain sequence set forth in SEQ IDNO: 10 ( see alignment in appendix B for the light chain SEQ ID NO: 13 of pertuzumab and SEQ ID NO: 10 of this application). Thus, pertuzumab comprises the CDRs of claim 3, variable regions of claim 8 and the heavy and light chains of claim 9.
See paragraph 91 for Gennaro et al for the definition of pertuzumab.
Gennaro et al performs oligosaccharide analysis of different pertuzumab samples. In the pertuzumab samples the G0 glycoform is present in the sample at 72.1, 63.6, 62.4, 70.3, 75.4,71.8, 73.3 and 69.7 (values in percent) in the respective pertuzumab samples. See paragraphs 252-257 and table 9.
Gennaro et al disclose a composition comprising the antibody and a pharmaceutically acceptable carrier. See paragraphs 202-210 under “therapeutic applications and uses”
Thus, claims 3-5, 8-9, and 17 are anticipated.
Regarding claims 11 -15, the content of a main peak in the pertuzumab antibody samples tested is at least 72%, 73.3%, 72.1% and 75.4% in the respective samples. See table 9 (percent peak area).
Gennaro et al teaches a method of treating cancer comprising administering the pertuzumab with a pharmaceutical carrier to a patient an effective dose of 420mg or 840mg per dose. See paragraphs 202-210 under “therapeutic applications and uses”.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1-3, 10, 11 and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gennaro et al.US 2014/0308277 10/16/2014 as evidenced by Allison et al. US20060165702, July 2006 cited previously in view of Luo et al. Glycoengineering of pertuzumab and its impact on the pharmacokinetic/pharmacodynamic properties. Sci Rep. 2017 Apr 11;7:46347. doi: 10.1038/srep46347.
The teachings of Gennaro et al is set forth above.
Gennaro et al does not disclose the antibody is expressed in CHO cells with FUT8 knocked out and does not disclose the antibody has a fucosylation level of 0-5%.
Luo et al disclose an antibody specifically binding to HER2 i.e. pertuzumab, wherein the pertuzumab is expressed by CHO cells with the FUT8 gene knocked out. Luo et al disclose a composition/pharmaceutical composition comprising phosphate buffered saline and pertuzumab wherein the pertuzumab has been purified from said CHO cells with the FUT8 gene knocked out. See p. 7 under preparation of glycoengineered pertuzumab and page 2 under characterization of pertuzumab expressed in Glycoengineered CHO cells. Luo et al disclose therefore said antibody will also have a fucosylation level of 0%. Moreover, Luo et al disclose knocking out the FUT8 gene results in an afucosylated (nonfucosylated) antibody. See abstract, p. 2 under “characterization of pertuzumab expressed in Glycoengineered CHO cells.
Luo et al disclose afucosylated pertuzumab has increased ADCC activity. See p. 1 last paragraph and p. 2 first paragraph.
Gennaro et al also discloses that ADCC activity is an aspect of cell mediated immunity by which an effector cell actively lyses a target cell that has bound antigen specific antibodies. Gennaro et al also discloses afucosylated variants of the pertuzumab. See paragraph 250.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date of the instant that the antibodies of Gennaro et al could have been expressed by a CHO cell with the FUT8 gene knocked out as taught by Luo et al, and would have resulted in the instant invention with a reasonable expectation of success. The motivation to have done so is that Luo et al discloses that expressing pertuzumab in a CHO cell with the FUT8 gene knocked out results in an afucosylated pertuzumab with increased ADCC activity i.e. 0% fucosylation and as taught by Gennaro et al ADCC activity is an aspect of cell mediated immunity by which an effector cell actively lyses a target cell that has bound antigen specific antibodies.
Expressing the pertuzumab in said CHO cells could have reasonably resulted in afucosylated pertuzumab at a fucosylation level of 0% (Luo et al disclose the pertuzumab expressed in FUT8 knocked out CHO cells is fucose (-).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 3, 6-9, 17, 18 and 23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9 and 10 of copending Application No. 18/855690 (‘690). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘690 claims disclose:
An antibody comprising the CDRs in claim 3, the variable regions of claim 8 and the heavy and light chain of claim 9.
The ‘690 claims discloses that the antibody comprises no less than 60% G0.
The ‘690 claims discloses that the antibody further comprises 3-7% G0-GN glycoform which overlaps with 5-6% in claim 7, 6-12% of G1 glycoform which anticipates 8-9% in claim 7, 6-12% G1’ glycoform which anticipates 8-9% in claim 7 and no more than 3% of G2 glycoform which anticipates 0-1% in claim 7.
The ‘690 claims disclose a method of treating cancer comprising administering to a patient an effective dose of said antibody.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-3, 10, and 18-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9 and 10 of copending Application No. 18/855690 (‘690) in view of Luo et al. Glycoengineering of pertuzumab and its impact on the pharmacokinetic/pharmacodynamic properties. Sci Rep. 2017 Apr 11;7:46347. doi: 10.1038/srep46347 and Gennaro et al.US 2014/0308277 10/16/2014.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘690 claims disclose:
An antibody comprising the CDRs in claim 1 and 3 and disclose that the antibody has a fucosylation level of 0-5%.
The ‘690 claims discloses that the antibody comprises no less than 60% G0.
The ‘690 claims disclose a method of treating cancer comprising administering to a patient an effective dose of said antibody.
The ‘690 claims disclose the antibody is pertuzumab.
The ‘690 claims do not disclose that the antibody is expressed by a CHO cell with FUT8 knocked out and does not disclose the effective dose of the antibody is 50 mg to 1000 mg per dose.
Luo et al disclose an antibody specifically binding to HER2 i.e. pertuzumab, wherein the pertuzumab is expressed by CHO cells with the FUT8 gene knocked out. Luo et al disclose a composition/pharmaceutical composition comprising phosphate buffered saline and pertuzumab wherein the pertuzumab has been purified from said CHO cells with the FUT8 gene knocked out. See p. 7 under preparation of glycoengineered pertuzumab and page 2 under characterization of pertuzumab expressed in Glycoengineered CHO cells. Luo et al disclose therefore said antibody will also have a fucosylation level of 0%. Moreover, Luo et al disclose knocking out the FUT8 gene results in an afucosylated (nonfucosylated) antibody. See abstract, p. 2 under “characterization of pertuzumab expressed in Glycoengineered CHO cells.
Luo et al disclose afucosylated pertuzumab has increased ADCC activity. See p. 1 last paragraph and p. 2 first paragraph.
Gennaro et al teaches a method of treating cancer comprising administering the pertuzumab to a patient an effective dose of 420mg or 840mg per dose. See paragraphs 202-210 under “therapeutic applications and uses”.
Gennaro et al also discloses that ADCC activity is an aspect of cell mediated immunity by which an effector cell actively lyses a target cell that has bound antigen specific antibodies. Gennaro et al also discloses afucosylated variants of the pertuzumab. See paragraph 250.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date of the instant that the antibodies of the ‘690 claims could have been expressed by a CHO cell with the FUT8 gene knocked out as taught by Luo et al, and would have resulted in the instant invention with a reasonable expectation of success. The motivation to have done so is that Luo et al discloses that expressing pertuzumab in a CHO cell with the FUT8 gene knocked out results in an afucosylated pertuzumab with increased ADCC activity i.e. 0% fucosylation and as taught by Gennaro et al ADCC activity is an aspect of cell mediated immunity by which an effector cell actively lyses a target cell that has bound antigen specific antibodies.
Expressing the pertuzumab in said CHO cells could have reasonably resulted in afucosylated pertuzumab at a fucosylation level of 0% (Luo et al disclose the pertuzumab expressed in FUT8 knocked out CHO cells is fucose (-).
With respect to claim 19, administering the antibody at a dose from 50 mg to 1000 mg to said patient would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date in view of the teaching of Gennaro et al that pertuzumab can be administered to a patient to treat cancer patient at an effective dose of 420mg or 840mg per dose.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Status of Claims
Claims 1-19 and 23 are rejected.
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/OLUWATOSIN A OGUNBIYI/ Primary Examiner, Art Unit 1645
1Taken from figure S1 of supplementary information of the following journal article: Senini et al. Direct glycosylation analysis of intact monoclonal antibodies combining ESI MS of glycoforms and MALDI-in source decay MS of glycan fragments. Commun Chem 7, 203 (2024). https://doi.org/10.1038/s42004-024-01297-x