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
Continued Examination Under 37 CFR 1.114
1. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 6/9/2026 has been entered.
Status of the Claims
2. Claims 1-50 are the original claims filed 7/21/2022. In the Response of 3/8/2023, claims 3-5, 7, 9, 16, 18, 24, 29, 32, 34, 42, 44, and 46 are amended, and claims 12-15, 17, 19- 23, 26-28, 30-31, 33, 38-41, and 48-50 are canceled. In the Reply of 8/14/2025, claim 29 is amended. In the Response of 12/30/2025, claims 1-3, 6-8, 10, 16, 45, and 47 are amended, claims 4, 11, and 18 are canceled, and new claim 51 is added. In the Response of 6/9/2026, claims 1 and 6-8 are amended and claim 47 is canceled.
Claims 1-3, 5-10, 16, 24-25, 29, 32, 34-37, 42-46, and 51 are all the claims.
Claims 35-37 are withdrawn.
Claims 1-3, 5-10, 16, 24-25, 29, 32, 34, 42-46, and 51 are the claims under examination.
The amendments to the claims raise new grounds for rejection.
Priority
3. USAN 17/759,282, filed 07/21/2022, and having 1 RCE-type filing therein, is a National Stage entry of PCT/CN2021/ 073347, International Filing Date: 01/22/2021, claims foreign priority to PCT/ CN2020/073960, filed 01/23/2020.
Information Disclosure Statement
4. As of 7/15/2026, a total of five (5) IDS are filed: 3/30/2023; 11/22/2024; 8/14/2025; 12/30/2025; and 6/9/2026. The corresponding initialed and dated 1449 form is considered and of record.
Withdrawal of Rejections
Claim Rejections - 35 USC § 112(b)
5. The rejection of Claims 1-3, 5-10, 16, 24-25, 29, 32, 34, 42-47, and 51 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is moot for canceled claim 47 and withdrawn for the pending claims. Claim 1 is amended to delete “at least a portion of” with respect to the hinge of the invention.
Claim Rejections - 35 USC § 112(a)
Written Description
6. The rejection of Claim 47 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 moot for canceled claim 47.
Claim Rejections - 35 USC § 103
7. The rejection of Claim(s) 1-3, 5-10, 16, 24-25, 29, 42-47, and 51 under 35 U.S.C. 103 as being unpatentable over Kannan et al (WO 2015/017548; 2/5/2015; Amgen) is moot for the canceled claim 47 and withdrawn for the pending claims.
Claim 1 is amended to delete “at least a portion of” an immunoglobulin hinge for what is understood to be any full hinge from any Ig irrespective of the isotype and the structure. Applicants discussion of examples with Ig hinge regions and substitutions N390C and S400C listed under elements 1-3 for the prototypes Mutation IDs TYM05, TYM10, TYM11 and TYM12 are alleged to improve heterodimer purity whereas the reference art uses hinge fragments instead. See p. 14 in the Response of 6/9/2026.
8. The rejection of Claim(s) 32(a) and 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kannan et al (WO 2015/017548; 2/5/2015; Amgen) as applied to claims 1, 16, 24 and 29 above, and further in view of Davis et al. (WO 2007/110205; 10/4/2007; MERCK PATENT GMBH) is withdrawn. See the comments for withdrawal in section 7.
Rejections Maintained
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.
9. The provisional rejection of Claims 1-3, 5-10, 16, 24-25, 29, 32, 34, 42-46, and 51 on the ground of nonstatutory double patenting as being unpatentable over claim 56 of copending Application No. 18/855,066 (reference application US 20250257133) is maintained for the pending claims.
Applicants request that the provisional rejection is held in abeyance is granted.
New Grounds for Rejection
Claim Rejections - 35 USC § 112
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.
Written Description/ New Matter
10. Claims 1-3, 5-10, 16, 24-25, 29, 32, 34, 42-46, and 51 are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim interpretation
Claim 1 is amended to delete “at least a portion of” an immunoglobulin hinge for what is understood to be any full hinge from any Ig irrespective of the isotype and structure. No structure for an Ig hinge region is instantly claimed.
Applicants discussion of examples with Ig hinge regions and substitutions N390C and S400C listed under elements 1-3 for the prototype Mutation IDs TYM05, TYM10, TYM11 and TYM12 are alleged to improve heterodimer purity. See p. 14 in the Response of 6/9/2026.
“hinge region”: is taught in the specification such as comprising mutations:
[0431] In addition, modifications may also be made within the Fc region of an illustrative antibody, typically to alter one or more functional properties of the antibody, such as serum half-life, complement fixation, Fc receptor binding, and/or antigen-dependent cellular cytotoxicity. In one example, the hinge region of CH1 is modified such that the number of cysteine residues in the hinge region is altered, e.g., increased or decreased. This approach is described further in U.S. Pat. No. 5,677,425. The number of cysteine residues in the hinge region of CH1 is altered to, for example, facilitate assembly of the light and heavy chains or to increase or decrease the stability of the antibody. In another case, the Fc hinge region of an antibody is mutated to decrease the biological half-life of the antibody.
“hinge”: there is no per se definition for the meaning a hinge in the specification.
The interpretation encompasses a genus of heterodimeric proteins beyond those taught in the specification. Because applicant seeks patent protection for all such proteins, this genus must be adequately described. A description adequate to satisfy 35 U.S.C. § 112(a) must clearly allow persons of ordinary skill in the art to recognize that the inventor invented what is claimed (Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc) (citation omitted, alteration in original). The purpose of the written description requirement is to “ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent’s specification” (In re Katz Interactive Call Processing Patent Litig. 639 F.3d 1303, 1319 (Fed. Cir 2011).
Scope of the claimed genus
Applicants disclosure does not define the meaning of a hinge. Applicants definition of a “hinge region” at [0431] may encompass any number and kind of amino acids that are natural or non-natural or even mimetics for any Ig hinge. The variation may encompass the presence of non-naturally occurring thiol groups, e.g., methionine or cysteine, which is potentially disadvantageous because these amino acids can lead to misfolding or mis-conjugation problems. The encompassed heterodimeric proteins are allowed to vary relative to 1st and 2nd polypeptides. The genus encompassed by the claims is therefore very large and there is substantial variation within the genus.
Summary of species disclosed in the specification
For purposes of brevity Applicants analysis is excerpted from the Response of 6/9/2026 where the comparative data are shown in Table 2:
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1110
1004
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Greyscale
No structure for an Ig hinge region is readily ascertainable from the sequences in the specification or the sequence listing on file. The amino acid sequences that correspond to Mutation IDs TYM05, TYM10, TYM11 and TYM12 are not readily ascertainable from the specification or the sequence listing on file much less are the corresponding hinge regions for each of the prototypes.
It is noted that the features upon which applicant relies (i.e., Ig hinge region/ N390C/S400C CH3 correlated with improvement in heterodimerization) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Are the disclosed species representative of the claimed genus?
It is asserted that the disclosed species are not representative of the claimed genus because the claims encompass all heterodimeric proteins having: any immunoglobulin hinge region; and N390C/S400C (CH3) that in combination promote heterodimerization of a 1st and 2nd polypeptide comprising any CH3 domain. The specification does not readily identify which Ig hinge combination with the N390C/S400C CH3 mutation promotes heterodimerization. Neither the specification nor the prior art provides guidance as to what structural changes can be made to the parent sequences and still predictably arrive at any heterodimeric protein. The disclosed species therefore do not represent the claimed genus.
It is asserted that neither the specification nor the state of art at the time of filing disclosed structural features common to the members of the genus for reliably assigning different antibody structures based on sequence data for two antibody clones, which would support the premise that the inventors possessed the full scope of the claimed invention.
Conclusion
11. No claims are allowed.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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, Wu Julie can be reached at 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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/LYNN A BRISTOL/Primary Examiner, Art Unit 1643
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