DETAILED ACTION
Status of Application, Amendments and/or Claims
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 of 7/20/26 has been entered in full. Claims 1-2, 4, 7 and 11-13 are amended. Claims 1-20 are pending.
Information Disclosure Statement
The Information Disclosure Statement of 7/20/26 has been considered.
Withdrawn Objections and/or Rejections
The following page numbers refer to the previous Office Action (1/21/26).
The objection to the drawings on page 2 is withdrawn in view of the replacement sheets filed on 7/20/26.
The objection to the specification at page 3 is withdrawn in view of the amendments to the specification.
The objections to claims 11-14 at page 3 under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only is withdrawn in view of the amendments to the claims.
The objections to claims 1, 3-10 and 15-20 at pages 3-4 are withdrawn in view of the amendments to the claims.
The rejection of claim 2 at page 4 under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter is withdrawn in view of the amendments to the claim.
The rejection of claim 2 at pages 6-9 under 35 U.S.C. 112(a) for lacking enablement for the full scope of the claim is withdrawn in view of the amendments to the claim that limit the binding molecule to one that comprises the sequence of SEQ ID NO: 15.
Maintained Objections and/or Rejections
Claim Objections
Claim 2 is objected to because of the following informalities:
In claim 2, line 2, “SEQ ID NO” should be “SEQ ID NO:”.
Appropriate correction is required. This objection was set forth at page 3 of the 1/21/26 Office Action.
Applicants’ reply filed on 7/20/26 at pages 9-10 indicates that the claim has been amended to overcome this objection, but the claims as filed on 7/20/26 do not include the referenced change. As such, the objection is maintained.
Claim Rejections - 35 USC § 112, enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.-The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1 and 3-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while enabling for
A binding molecule comprising a human IgG1 Fc variant of a wild-type human IgG1 Fc region and one or more antigen binding domains, wherein the Fc variant comprises the amino acid sequence of SEQ ID NO: 15,
does not reasonably provide enablement for
A binding molecule comprising a human IgG1 Fc variant of a wild-type human IgG1 Fc region and one or more antigen binding domains, wherein the Fc variant comprises a combination of amino acid substitutions consisting of L234A, L235A, S267K and P329A (LALSKPA), wherein the amino acid residues are numbered according to the EU index of Kabat, and wherein the Fc variant leads to a reduced or undetectable binding affinity to FcγRIA, FcγRIIIa or C1q relative to wild-type IgG1 Fc region.
This rejection was set forth at pages 6-9 of the 1/21/26 Office action for claims 1, 3-10 and 15-20; Applicants’ amendments to claims 11-14 necessitate the addition of these claims to the rejection.
In the reply at page 11, Applicants argue that claim 1 has been amended to “further narrow and expressly define the invention”, and such amendment “substantially narrows the claim scope and directly addresses the concerns raised in the Office Action”. Applicants further argue that “[t]he present amendment removes any such concern” that the claims encompass “a broad genus of Fc variants extending beyond the specific molecules disclosed in the application and therefore require undue experimentation to determine which variants possess the claimed properties” (pages 11-12). Applicants further argue that the claim “no longer encompasses an open-ended genus of Fc variants” and instead is “limited to Fc variants comprising a specific combination of four defined amino acid substitutions”, i.e., LALASKPA.
This argument has been fully considered but is not found persuasive. The amendments to lines 3-4 of claim 1 merely correct grammar that was objected to. The amendments to lines 6-7 of claim 1 introduce a new functional limitation that does not address the basis of the enablement rejection; specifically, that the Fc region of the binding molecule of claim 1 is not limited to the set of four substitution mutations termed LALASPKA (i.e., those found in SEQ ID NO: 15) but instead encompasses an Fc region with those mutations as well as any other number of mutations throughout the sequence. As set forth in the rejection of record at page 7 of the previous Office action, the specification expressly teaches that a “variant Fc region” differs by “at least one amino acid”, which is a range without an upper limit, and thus the claims encompass variant in which each and every amino acid of the 217 amino acid sequence is altered. The addition of a functional limitation only serves to identify a property that must be tested for and does not identify which mutations can be made throughout the amino acid sequence of SEQ ID NO: 15 and still retain functionality. Prior art (Borrok et al, 2017) was cited that mutations into the Fc region may result in unintended loss of functionality including “a reduction in biophysical stability which can correlate with increased aggregation propensity, poor manufacturability, and lower solubility”; see page 8 of the previous Office action. It is noted that dependent claim 2 as amended is now limited to comprising the amino acid sequence of SEQ ID NO: 15 and thus does now meet the enablement requirement.
At pages 12-13, Applicants further argue that the specification provides experimental guidance demonstrating that the recited functional properties (Fc receptor and C1q binding) are possessed by WT IgG1 as well as the mutants LALASKPA, LALAPA, LALAGA, LALAPG, DAPASK, GADAPA and GADAPASK. At page 13, Applicants point to original Figures 2 and 3 (now renumbered as Figures 2-5). Applicants further point to teachings in the specification regarding how to measure “reduced Fc receptor binding and C1q binding”.
This argument has been fully considered but is not found persuasive. These results were previously considered and acknowledged at page 8 of the previous Office action, but they are limited to testing the effector function and not whether other mutations, encompassed by the claims, result in loss of functionality of the Fc region. With regard to the techniques for measuring reduced Fc receptor and C1 binding, these are limited to measuring these particular functional properties and not to determine the effect of other mutations on functionality.
Double Patenting
The nonstatutory double (NSDP) 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 NSDP 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 (TD) in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on NSDP 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 TD must be signed in compliance with 37 CFR 1.321(b).
The filing of a TD by itself is not a complete reply to a NSDP rejection. A complete reply requires that the TD 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 TD 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 (eTD) may be filled out completely online using web-screens. An eTD that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTDs, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-9 and 11-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 169-196, 199-202 and 204 of co-pending application 18/035,470, filed 5/4/23, and which shares the same applicant and includes the same two inventors with the instant application. This rejection was set forth at pages 10-13 of the 1/21/26 Office Action; Applicants’ amendments to the claim necessitate the addition of claims 11-14 to the rejection.
Instant claim 1 has been amended to add a functional limitation to the claimed binding molecule; specifically, that the Fc variant that it comprises is one that “leads to a reduced or undetectable binding affinity to FcγRIA, FcγRIIIa or C1q relative to a IgG1 Fc region”. Applicants argue at page 15 of the 7/20/26 reply that this amendment to claim 1 renders the claim patentably distinct from the claims of the ‘470 application.
This argument has been fully considered but is not found persuasive. The antibodies of ‘470 containing Fc regions that comprise the LALASKPA mutations inherently possess the newly recited functional limitation that is conferred by the LALASKPA mutations. Furthermore, the specification of ‘470 provides evidence of this. See Section 8.34 Example 34. As such, while the claims of ‘470 do not expressly recite the new limitation, the claimed subject matter inherently possesses it.
Claims 11-14, as amended, encompass a method of treating a disease in an individual comprising administering the binding molecule of claim 1 to the individual, wherein the effector function of the binding molecule is reduced or undetectable in the individual compared to the effector function induced by a polypeptide comprising the wild-type human IgG1 Fc region (claim 11), and further wherein the effector function is ADCC (claim 12), ADCP (claim 13) or CDC (claim 14). These claims correspond to claim 204 of ‘470, which is directed to a method of treating a subject with a CD19-associated disease or disorder comprising administering to the subject an effective amount of the CD19-binding molecule of claim 169. While these claims do not expressly recite the functional limitation directed to effector function, the CD19-binding molecule of claim 169 that comprises an Fc region comprising the LALASKPA mutations would inherently possess this functionality, as evidenced by the specification of ‘470; see Section 8/34 Example 34 cited above.
Claims 1-8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 136-142 of co-pending application 18/035,472, filed 5/4/23, and which shares the same applicant and includes the same two inventors with the instant application. This rejection was set forth at pages 13-15 of the 1/21/26 Office Action.
Instant claim 1 has been amended to add a functional limitation to the claimed binding molecule; specifically, that the Fc variant that it comprises is one that “leads to a reduced or undetectable binding affinity to FcγRIA, FcγRIIIa or C1q relative to a IgG1 Fc region”. Applicants argue at page 15 of the 7/20/26 reply that this amendment to claim 1 renders the claim patentably distinct from the claims of the ‘472 application.
This argument has been fully considered but is not found persuasive. The antibodies of ‘470 containing Fc regions that comprise the LALASKPA mutations inherently possess the newly recited functional limitation that is conferred by the LALASKPA mutations. Furthermore, the specification of ‘472 provides evidence of this. See Section 8.34 Example 34. As such, while the claims of ‘472 do not expressly recite the new limitation, the claimed subject matter inherently possesses it.
While this rejection is currently provisional, it is noted that a Notice of Allowance was mailed on 9/15/26 in the ‘472 application, and includes claims 136-142, and that once a patent is issued this rejection will necessarily become non-provisional.
New objections
Claim Objections
Claims 1-20 are objected to because of the following informalities:
In claim 1, lines 6-7, “wild-type IgG1 Fc region” is missing an article (“a” or “the”).
In claim 4, line 6, “is Fc gamma RIIIa V158 variant” should be “is a Fc gamma RIIIa V158 variant”.
In claim 13, line 1, “wherien” should be “wherein”.
In claims 7 and 14, “complement dependent” should be “complement-dependent”. Compare with “antibody-dependent” in claims 7, 12 and 13.
The remaining claim(s) are objected to for depending from an objected claim.
Appropriate correction is required.
New rejections necessitated by Applicants’ amendment
Claim Rejections - 35 USC § 112(b)
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 1-20 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 pre-AIA the applicant regards as the invention.
Claim 1, as amended, newly recites a “wild-type IgG1 Fc region” in lines 6-7. It is unclear whether or not this region is the same one recited in lines 1-2, because the region of lines 6-7 is missing an article, and is also lacks the word “human”.
The remaining claim(s) included in the rejection are dependent claims that depend from one of the claims rejected above and encompass the same indefinite subject matter.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 extension fee 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 ZACHARY C HOWARD whose telephone number is (571)272-2877. The examiner can normally be reached on Monday to Friday from 9 AM to 5 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford, can be reached at telephone number (571) 272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZACHARY C HOWARD/Primary Examiner, Art Unit 1674
