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. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 May 15, 2026 has been entered.
Claims 3-5, 8, 11, and 14 have been canceled.
Claim 21 has been added.
Claims 1, 2, 6, 7, 9, 10, 12, 13, and 16-21 are pending.
Claims 16-20 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as
being drawn to nonelected inventions, there being no allowable generic or linking claim.
Election was made without traverse in the reply filed on December 23, 2024.
Claims 1, 2, 6, 7, 9, 10, 12, 13, 15, and 21 are currently under consideration.
3. Claims 1, 2, 6, 7, 9, 10, 12, 13, 15, and 21 are objected to for following informalities:
Independent claim 1 recites “wherein amino acid residue other than an arginine residue and a lysin residue” in lines 3-4, which appears to be a typographic error in that it omitted the EU position, e.g. wherein the amino acid residue at position 334 according to the EU numbering system is an amino acid residue other than arginine and lysine (see previous claim set filed on April 20, 2026).
4. 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.
5. Claims 1, 2, 6, 7, 9, 10, 12, 13, and 15, and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14 and 16-21 of copending USSN 18/756,956 (the ‘956 application) in view of Presta (US 6,737,056) for the reasons of record.
The Office Actions mailed previously, e.g. on February 19, 2026, addressed this rejection including K334H substitution as summarized below:
The instant claims are drawn to an antibody half molecule comprising a hinge region, a CH2 region and a CH3 region, wherein at least one cysteine in the hinge region is substituted with another amino acid residue in position C226 and C229, wherein the amino acid residue at position 334 is an amino acid residue such as histidine (H) but not arginine (R) or lysine (K), and wherein homodimerization of the antibody half-molecule is inhibited (e.g. Dependent claim 2).
The claims in the ‘956 application are drawn to a method of treating a disease by a pathogenic cell in a subject by administering a first polypeptide comprising a first antigen binding domain, and a first IgG Fc domain comprising a CH3 domain and a second polypeptide comprising a second antigen binding domain and a second IgG Fc domain, wherein the first Fc comprises amino acid substitution V397Y/K409D (in claim 14), K334E (in claim 19), and C226S and C229S (in claim 20).
The claims in the ‘956 application differ from the instant invention by not reciting amino acid substitution in position 334 with the amino acid residues including H.
Presta teaches a human IgG1 Fc variant consisting of K334Q, K334E, K334H. K334M, K334Y, or K334L, all increased binding affinity to the activating FcγRIIIa, indicates increased ADCC activity (e.g. see variants 136, 139, 190, 191, 221 in Table 8 in cols 63-64).
It would thus be obvious to replace K334E substitution recited in the claims of the ‘956 application with well-known residues as taught by Presta including K334Q, K334E, K334H. K334M, K334Y, or K334L, all of which can enhanced Fc’s affinity to FcγRIIIa and enhanced ADCC effect similar to K334E. An ordinary skill in the art would have been motivated to do so, and have a reasonable expectation of success, since Presta teaches substitutions in K334 with amino acid residues listed above would be expected to enhance effector function. As such, the copending claims in the ‘956 application would render the instant claim 21 obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant asserts that the instant claims are drawn to antibody half-molecule having specific structural modifications required to achieve the half-molecule. Applicant asserts that the stable antibody-half molecule recited in the instant claims differ from the claims in the ‘956 applicant in that the conflicting claims are drawn to pharmaceutical composition comprising the combination of two different antigen-binding molecules that are “more likely to form a heterodimer than homodimers when mixed in solution, and modification in positions 397 and 409 in the conflicting claims are used to promote heterodimerization, rather than forming antibody half-molecule. Applicant asserts that the specific modifications in the instant claims are not recited or suggested in the claims of the ‘956 application in view of Presta which teaches same modification K334E or K334H for enhanced ADCC but not to stabilize antibody half-molecule. Applicant asserts that the instant claims require modification at position 334 to other amino acid residues including H but not K or R or E while claim 19 in the ‘956 application allows K334E. Applicant also argues that instant claim 1 recites that at least one cysteine to be substituted with a serine among positions 226 and 229 but independent claim 14 in the ‘956 application merely recites the first and second polypeptide are not linked by a covalent bond but the mutations in 226 and 229 are only recited in dependent claim 20. Applicant asserts that it is improper to interpretate an antibody half-molecule” comprising a hinge region, a CH2 and CH3 to have additional H chain components since the claim 14 of the ‘956 applicant also requires capable of forming heterodimers in surface plasmon resonance assay.
As such, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
Contrary to applicant’s arguments, note that the issue remains to be that the specific modifications recited in the instant claims are also recited in the conflicting claims in the ‘956 application. For example, independent claim 14 recites a method for treating a disease by administering simultaneously or sequentially to the subject a first polypeptide and a second polypeptide. Clearly, the two polypeptides are not dimerized when administered sequentially.
Further, dependent claim 16 of the ‘956 applicant recites second CH3 domain comprises V397Y/K409D substitutions (identical to the modification recited in the instant claims) and dependent claim 19 further recite that the second CH3 further comprises K334E substitution. Dependent claim 20 further recite that the second IgG comprises C226S and C229S substitution. Furthermore, the specification of the ‘956 application explicitly disclose that these modifications are intended to create antibody half-molecule when no antigen binding occurs (e.g. see [0017] of the specification as-filed of the ‘956 application) and also discloses that the well-known modifications in V397 and K409 weaken the interaction at CH3 interface (e.g. see [0162] of the specification as-filed of the ‘956 application).
While the claims in the ‘956 applicant recites K334E substitution but not K334H, the substitution in position 334 of the Fc region of a human IgG1 for enhanced effector functions including enhanced binding to FcγRIIIa and enhanced ADCC activity were well known in the art at the time the instant invention was filed as evidenced by the teachings of Presta (teaches K334Q, K334E, K334H. K334M, K334Y, or K334L, all increased binding affinity to the activating FcγRIIIa, indicates increased ADCC activity, see discussion above).
It would thus be obvious to one of skill in the art at the time the instant invention was filed to combine the teachings of Presta to replace K334E in the ‘956 application with anyone of the amino acid substitution K334Q, K334H. K334M, K334Y, or K334L for enhanced FcγRIII binding and enhanced ADCC effect as taught by Presta. One of ordinary skill in the art would have been motivated to do so, and have a reasonable expectation of success, since Presta teaches K334Q, K334E, K334H. K334M, K334Y, or K334L in the Fc region of a human IgG1 antibody can also increase Fc’s affinity to the activating FcγRIIIa and enhanced ADCC activity, replacing K334E in the claims of the ‘956 application with another well known modification such as K334H would be well-within the skill of an ordinary artisan.
Given that the combined teachings of the references would result in the same modifications as the instant antibody half molecule, the prior art antibody half molecule would inherently/intrinsically have the same functions including destabilized conformational interface in the CH3 region.
As such, applicant’s arguments have not been found persuasive.
6. No claim is allowed.
7. All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
8. 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
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