DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s amendment filed on October 7, 2025 is acknowledged.
Claims 2-4, 6-16, and 23-63 have been canceled.
Claims 1, 5, and 17-22 are pending and currently under consideration.
3. 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 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.
4. 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, 14, and 17-22 are rejected under 35 U.S.C. 103 as obvious over Vermot-Desroches et al. (WO2014/009358, reference on IDS) in view of Parren et al. (WO 2014/108198, reference on IDS) for the reasons of record.
The previous Office Action states:
“Vermot-Desroches et al. teach TRAIL Receptor 1 (TRAILR1, DR4) that has a cytoplasmic death domain and are able to trigger apoptosis in tumor cells via down-stream caspase activation (e.g. see [0005] in pages 1-2). Vermot-Desroches et al. teach expression of DR4 is frequently detected in human cancers including colon, gastric, pancreatic, ovarian, breast and non-small-cell lung cancer with low or no expression in normal tissues (e.g. see [0007] in page 2). Vermot-Desroches et al. teach that agonistic monoclonal anti-DR4 antibody directed against DR4 including bispecific antibody against DR4 and DR5 can be used for cancer therapy (e.g. see [0015]-[0018]). Vermot-Desroches et al. teach that anti-DR4 agonist antibodies including mapatumumab (anti-DR4 human IgG1 antibody) or lexatumumab are shown to be well-tolerated in patients (e.g. see [0020]) in page 4. Vermot-Desroches et al. teach that a synergistic apoptosis induction against glioma has been observed by using two antibodies each directed to a different epitope on the DR5 as compared to one antibody against one single epitope and teach a pharmaceutical composition comprising these two antibodies (e.g. see page 5). Vermot-Desroches et al. also teach that the antibodies can exhibit cytotoxicity mediated by the Fc region including CDC and modification in the Fc region to increase CDC function is desirable (e.g. see page 19). Vermot-Desroches et al. disclose examples of specific anti-DR5 antibody (e.g. see page 5).
The reference teachings differ from the instant invention by not method of increasing the apoptotic activity of the anti-DR4 antibody by introducing E430G amino acid substitution in the Fc region.
Parren et al. teach method of making a human IgG1 including IgF1m(f) isoform antibody with enhanced complement-dependent cytotoxicity (CDC) by introducing amino acid substitution in the Fc region in position E430 including E430G (e.g. see 2nd full paragraph in pages 3, 21-22, 2nd full paragraph in page 23, and Figures 2 and 31). Parren et al. teach that the antibody can be human monoclonal antibodies such as IgG1-4 (e.g. see Figure 2 in page 5) or humanized or chimeric (e.g. see pages 9-12). Parren et al. teach that the antibody can be targeting to antigen TNFRSF10A which known to be death receptor 4 (DR4) (e.g. see pages 39 and 46). The reference teaches a pharmaceutical composition comprising the antibodies and a carrier and a kit (e.g. see pages 68-71). Parren et al. teach multispecific and bispecific antibody (e.g. see page 70). Given that the prior art antibody binds the same DR4 and has the same amino acid substitution E430G in the Fc region, the prior art antibody would inherently be agonistic and capable of inducing programmed cell death in a target cell.
It would thus be obvious to one of ordinary skill in the art at the time the invention was filed to combine the teachings of Vermot-Desroches et al. and Parren et al. to introduce the E430G substitution to the Fc region of an antibody including anti-DR4 antibody for increase CDC activity of the antibody. Such antibody would be expected to have increased apoptotic activity compared to the same antibody without E430G substitution because it was shown by Parren et al. that E430G substitution in the Fc region of an IgG1 antibody including anti-DR4 antibody enhanced the cell killing via increased CDC activity compared to the unmutated antibody. An ordinary skill in the art would have been motivated to introduce E430G substitution in the Fc region of a human anti-DR4 IgG1 antibody for increased tumor cell killing, and have a reasonable expectation of success, since amino acid substitution E430G in the Fc region of a known anti-DR4 and/or anti-DR5 antibody would be expected to increase the cytotoxicity of the antibody by increase effector functions such as CDC activity. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary”
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant argues that the claims have been amended to recite an antibody that binds to DR4 which renders the claim unobvious because a skilled artisan would not have considered introducing E430G into an anti-DR4 antibody to increase its apoptotic activity. Applicant asserts that the CDC and apoptosis are different methods of killing cells involving different mechanisms, specifically, CDC involves the physical lysis of cells as a result of pores formed in the cell membrane while apoptosis refers to the programmed cell death rather than pore-based lysis of cells. As such, applicant asserts that a skilled in the art would not have looked to the disclosure of Parren et al., which teaches E430G substitution for increased CDC activity, for the purpose of increased apoptosis effect. As such, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
Contrary to applicant’s reliance on the distinction of apoptosis vs CDC, note that the instant claims are drawn to a method for increasing the apoptotic activity of an anti-DR4 antibody, the method comprising a single step of introducing into the Fc region of the antibody a mutation at position E430, wherein the antibody induces higher level of apoptosis relative to the same antibody without the mutation.
It appears that the body of the claims defines the method steps and structure – introducing mutation at position E430 in the Fc region. But the preamble only states a purpose or intended use of the anti-DR4 antibody comprising substitution at E430 including E430G. As such, the preamble of “a method for increasing the apoptotic activity” does not limit the claims method steps and the structure of the antibody. See MPEP 2111.02(II).
The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See MPEP 2144 IV.
Here, given the teachings of Vermot-Desroches et al. pertinent to the benefit of an CDC enhanced specific anti-DR4 and anti-DR5 antibodies in killing tumor cells, and the teachings of Parren et al. regarding an IgG antibody, e.g. anti-DR4 antibody, with enhanced complement-dependent cytotoxicity (CDC) having amino acid substitution E430G in the Fc region, an ordinary artisan at the time the invention was filed would have had a reasonable expectation of success of combining the teachings of the references to modify single amino acid at position E430 with G in the well-known agonistic anti-DR4 antibody and anti-DR5 antibody to enhance tumor killing. Given that the properties of a compound cannot be separated from the compound, see In re Papesch, 315 F.2d 381,391 (CCPA 1963) (“a compound and all its properties are inseparable), the combined teachings of the references would have yielded an agonistic anti-DR4 or anti-DR5 antibody comprising E430G substitution in the Fc region inherently/intrinsically having the property of inducing a higher level of apoptosis relative to the same antibody without the E430G mutation.
As such, applicant’s arguments have not been found persuavive.
6. 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.
7. Claims 1, 5, 14, and 17-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 14-16, 18, 19, 21, 34, 38, and 46-50 of copending USSN 17/745,667) (the ‘667 application) in view of Parren et al. (WO 2014/108198, reference on IDS).
The instant claims are drawn to a method for increasing the apoptotic activity of a human IgG1 anti-DR4 antibody comprising introducing into the Fc region mutations E430G.
The claims in the ‘667 applicant are drawn to a polypeptide comprising a human IgG Fc region comprising mutations including E430G and wherein the polypeptide can be a human antibody that binds TNFR-SF (DR4) and the method of treating a disease by administering the polypeptide.
The claims in the ‘667 application differ from the instant claims by not reciting a method of increasing the apoptotic activity by introducing E430G substitution in the Fc region of a human IgG1 anti-DR4 antibody.
The teachings of Parren et al. are discussed above.
It would thus be obvious to one of ordinary skill in the art to practice a method of increasing apoptotic activity by using the polypeptide including anti-DR4 antibody comprising E430G substitution recited in the ‘667 application. An ordinary skill in the art would have been motivated to do so, and have a reasonable expectation of success, since Parren et al. teach that introducing E430G in the Fc region of an antibody such as anti-DR4 antibody would enhanced tumor cell killing via CDC activity. As such, one of skill in the art would be motivated to practice a method of increasing the apoptotic activity of a known anti-DR4 antibody by introducing substitution E430G in the Fc region known to increase tumor cell killing via CDC. As such, the claims in the ‘667 application would render the instant claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant requests that the provisional nonstatutory double patenting rejection be held abeyance. As such, the rejection is maintained for the reasons of record.
8. No claim is allowed.
9. 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.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHUN DAHLE whose telephone number is (571)272-8142. The examiner can normally be reached Mon-Fri 6:30am-4:00pm.
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, Misook Yu can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHUN W DAHLE/Primary Examiner, Art Unit 1641