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 .
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 July 9, 2026, has been entered.
The amendment filed July 9, 2026, is acknowledged and has been entered. Claim 23 has been amended. Claims 24-27 have been canceled.
Claims 23 and 28-44 are pending in the application. Claims 28-41 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected species of the invention, there being no allowable generic or linking claim.
Claims 23 and 42-44 are under examination. The species of heteromultimer with a specific combination of substitutions with a first CH3 with a K370D substitution and a K360E substitution and a second CH3 with E357K substitution is under consideration.
Information Disclosure Statement
The information disclosure statement has been considered.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 23 and 42-44 are rejected under 35 U.S.C. 102(a)(1) or 35 U.S.C. 102(a)(2) as being anticipated by Liu et al (US 2014/0112926 A1).
With respect to claims 23 and 42-43, Liu et al disclose methods of modifying IgG1 Fc regions using genetic engineering techniques and PCR that include making an amino acid modification in a first CH3 domain of K370D and K360E and making amino acid modifications in a second CH3 domain of E357K wherein the numbering is according to the EU index (see entire document, e.g., pages 6 and 10-12).
With respect to claim 44, Liu et al disclose that the heterodimer can be a bispecific or multispecific antibody (see pages 6, 11, 13, in particular ¶ 50, 59 and 69 and claims).
In particular, ¶ 59 states, in part:
“… the antibodies or Fc fusion proteins described herein, which comprise an Fc region, can contain one or more of the following particular amino acid substitutions in one or both of the A chain and the B chain that make up the Fc region: E233L, L234I, L234Y, L235S, G236Y, S239D, S239E, S239N, S239T F243M, F243L, F243V, F2431, K246W, K246E, K246S, K246V, K248Y, K248L, M252D, I253V, 1253K, R255S, R255N, T256V, T256Q, E258S, E258V, H268E, H268K, A287F, K288T, K2881, K290G, K290F, K290S, K290W, K290O, K290Y, E294L, Y296W, Y296L, S298A, S298C, S298T, V302Q, T307P T307S, T307E, T307G, L309C, L309S, L309K, L309E, Q311M, N315A, N315S, A330H, A330F, A330M, 1332E, K334L, K334V, K334A, K334M, A339T, K340N, R355D, R355E, E356K, E356R, D356K, D356R, E357K, E357R, K360D, K360E, K370D ...”
“In addition, any of the above proteins can comprise additional alterations such as heterodimerizing alterations.”
Then with respect to the intended use of the preamble of stabilizing the heteromultimer at about pH 5.0, as set forth in MPEP 2103:
The following types of claim language may raise a question as to its limiting effect:
(A) statements of intended use or field of use, including statements of purpose or intended use in the preamble,
(F) terms with associated functional language.
Accordingly, intended use or terms with associated functional language recited in the body of the claim also raises a question as to its limiting effect. While the claim has been amended to append the intended use onto the process step and recites functional language, the process step still stands on its own because the method step recites introducing an amino acid modification at position K360 of the CH3 domain to achieve the intended use of stabilizing (functional language) the heteromultimer at about pH 5.0. This appended phrase could also be characterized as an intended result (as evidenced by Applicant’s reply that the amendment was made “to clarify the purpose of introducing the K360 modification”, but merely reciting an intended result also does not distinguish a method claim from the prior art when it simply expresses the intended result of a process step positively recited (see MPEP 2111.04). The amino acid modification at position K360 of the CH3 domain achieves the use or result, so prior art that teaches the same modification also must necessarily achieve the same use or result.
Accordingly, Liu et al anticipate the claims absent a showing otherwise.
Applicant has traversed the rejection arguing that “Liu does not disclose, in any single embodiment, a first CH3 domain polypeptide having both K370D and K360E substitutions together with a second CH3 domain polypeptide having an E357K substitution. Liu pairs K370D with E357K but without any K360E modification. To arrive at the combination recited in claim 23 as amended would require impermissibly picking and choosing K360E from one part of Liu's lists and combining it with a separate charge-pair combination. Such picking and choosing from disparate portions of a reference cannot support anticipation.”
In response, it is first noted that the instant claims recite “open” language such that the claims encompass any number of additional Fc amino acid substitutions in one or both of the first CH3 chain and the second CH3 chain, such as those disclosed in paragraph [0059] of the prior art. Furthermore, paragraph [0059] of the prior art discloses that “the antibodies or Fc fusion proteins described herein, which comprise an Fc region, can contain one or more of the following particular amino acid substitutions in one or both of the A chain and the B chain that make up the Fc region”. The plain reading of this disclosure is that it discloses making each and every combination of “amino acid substitutions in one or both of the A chain and the B chain that make up the Fc region” set forth in this paragraph such that the prior art clearly anticipates the claimed method.
As set forth in MPEP 2145. “Granting a patent on the discovery of an unknown but inherent function "would remove from the public that which is in the public domain by virtue of its inclusion in, or obviousness from, the prior art." 596 F.2d at 1022, 201 USPQ at 661.)” In this case, granting the claimed methods would prevent others from using the methods of modifying IgG1 Fc regions using genetic engineering techniques and PCR that include making an amino acid modification in a first CH3 domain of K370D and K360E and making amino acid modifications in a second CH3 domain of E357K wherein the numbering is according to the EU index, disclosed by Liu. Notably, should the instant claims be allowed Applicant could attempt to prevent the public from using methods of producing heterodimeric antibodies comprising introducing an amino acid modification at position K360E wherein: (i) the first CH3 domain polypeptide comprises an amino acid modification at position K370, wherein the amino acid modification at position K370 is K370D, and (ii) the second CH3 domain polypeptide comprises an amino acid modification at position E357, wherein the amino acid modification at position E357 is E357K which are disclosed in the prior art application publication, and which could have been claimed in that application, if so desired. Thus, it is believed the rejection is proper, and the rejection is being maintained.
Conclusion
No claims are allowed.
All claims are drawn to the same invention claimed in the application prior to the entry of the submission under 37 CFR 1.114 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 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 Brad Duffy whose telephone number is (571) 272-9935. The examiner works a flexible schedule.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Julie Wu can be reached on (571) 272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Respectfully,
Brad Duffy
571-272-9935
/Brad Duffy/
Primary Examiner, Art Unit 1643
August 27, 2026
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