Notice of Pre-AIA or AIA Status
1. 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
Election/Restrictions
2. Applicant's election without traverse of Group I, claims 1-11, 14-20, 22, 24-26, 29-31, 35-38, 49 and 51-54, in the reply filed on 10 December 2025 is acknowledged. Applicant’s election of SEQ ID NO: 30 as the species of first polypeptide, SEQ ID NO: 31 as the species of second polypeptide, SEQ ID NO: 32 as the species of third polypeptide, SEQ ID NO: 2 as the species of CM1, SEQ ID NO: 14 as the species of CM2, and HBPC of complex 67 as the species of single molecular embodiment is also acknowledged. Claims 39 and 43-48 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and/or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10 December 2025.
3. The restriction requirement is still deemed proper and is therefore made FINAL.
Status of Application, Amendments, and/or Claims
4. The Response to the Restriction Requirement filed 10 December 2025 has been entered in full. Claims 39 and 43-48 have been withdrawn as discussed supra. Therefore, claims 1-11, 14-20, 22, 24-26, 29-31, 35-39, 43-49 and 51-54 are pending, and claims 1-11, 14-20, 22, 24-26, 29-31, 35-38, 49 and 51-54 the subject of this Office Action.
Information Disclosure Statement
5. The information disclosure statement (IDS) submitted on 30 June 2023 has been considered by the Examiner.
Claim Rejections - 35 USC § 112
6. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
7. Claim 49 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. In the instant case, the intended use recited in claim 49 does not further limit the activatable bispecific polypeptide complex recited in claim 1. Therefore, claim 49 fails to further limit the claim from which it depends (claim 1) by altering the structure or adding additional components. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112
8. 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.
9. Claims 11 and 38 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
10. Claim 11 recites the limitation "HR2" in line 3 of the claims. There is insufficient antecedent basis for this limitation in the claim. Claim 1, from which claim 11 depends, does not recite “HR2”.
11. Claim 38 is considered indefinite because a kit, by definition, must contain 2 or more elements and the interrelationships between the elements must be explicitly stated (see In re Venezia 530 F.2d 956 CCPA 1975).
Claim Rejections - 35 USC § 112, 1st Paragraph (Written Description)
12. The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
13. Claims 1-11, 14-20, 22, 24-26, 29-31, 35-38, 49 and 51-54 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
14. The U.S. Court of Appeals for the Federal Circuit recently reaffirmed, in an en banc decision, that the written description requirement for a genus may be satisfied either by (i) the disclosure of a representative number of species falling within the scope of the genus or (ii) structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus. Ariad Pharmaceuticals', Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1350, 94 U.S.P.Q.2d 1161, 1171 (en banc) (Fed. Cir. 2010), citing Regents" of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568-69, 43 U.S.P.Q.2d 1398, 1406 (Fed. Cir. 1997).
15. The representative ways of satisfying the written description requirement as set out by the Federal Circuit in Ariad Pharmaceuticals comport with statements set out in the USPTO's Manual of Patent Examining Procedure (M.P.E.P.). In particular, the M.P.E.P. provides that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species of relevant identifying characteristics. M.P.E.P. § 2163, II, A, 3, (a), (ii).
16. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed, and correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art. “Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP § 2163.
17. The claims are drawn very broadly to an activatable heteromultimeric bispecific polypeptide complex (HBPC) comprising:(a) a first polypeptide comprising (i) a single-chain variable fragment (scFv) comprising a first heavy chain variable domain (VH1) and a first light chain variable domain (VL1), wherein the VH1 and the VL1 together form a first targeting domain that specifically binds a first target, (ii) a first masking moiety (MI1), (iii) a first cleavable moiety (CM1); (iv) a second heavy chain variable domain (VH2), and (v) and a first monomeric Fc domain (Fc1); (b) a second polypeptide that comprises (i) a second light chain variable domain (VL2), wherein the VH2 and the VL2 together form a second targeting domain that specifically binds a second target, (ii) a second masking moiety (MM2), and (iii) a second cleavable moiety (CM2); and (c) a third polypeptide that ii)comprises a second monomeric Fc domain (Fc2) and (ii) does not comprise an immunoglobulin variable domain. The claims also recite wherein the first target is a T-cell antigen polypeptide, and the second target is a cancer cell surface polypeptide. The claims also recite wherein the MM1 and/or the MM2 comprises between about 5 amino acids to about 40 amino acids. Thus, the claims have been broadly interpreted by the Examiner as reading upon an extremely large genus of activatable bispecific polypeptide complexes that are only defined by a desired function/activity.
18. For genus claims, an adequate written description of a claimed genus requires more than a generic statement of an invention's boundaries. A patent must set forth either a representative number of species falling within the scope of the genus or structural features common to the members of the genus. Kubin, Exparte, 83 USPQ2d 1410 (Bd. Pat. App. & Int. 2007); Ariad Pharms., Inc. v. Eli Lilly& Co., 598 F.3d 1336, 1350 (Fed. Cir. 2010).
A “patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”), see MPEP 2163.IIAii.
19. Several recent court decisions speak to the notion that claiming a molecule with unknowable structural heterogeneity solely by reciting its function is not sufficient to establish possession of a genus so claimed.
20. For example, quoting Eli Lilly the court states in Ariad, 598 F.3d at 1350: "[A] sufficient description of a genus requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus." (quoting Eli Lilly, 119 F.3d at 1568-69).
21. A "representative number of species" means that the species which are described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG V. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.").
22. Likewise, the Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., high affinity, neutralization activity, competing with a reference antibody for binding, binding to a certain epitope), "[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. V. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
23. The Federal Circuit has clarified Written Description as it applies to antibodies in the recent decision Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. 112(a) (or pre-AlA first paragraph) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called “newly characterized antigen” test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the “newly characterized antigen” test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad, 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of an antigen alone is not considered adequate written description of a claimed antibody to that antigen, even when preparation of such an antibody is routine and conventional. Id.
24. In the instant case, the claims encompass in their breadth the activatable bispecific polypeptide complexes comprising two separate antigen binding regions that bind two different targets, said first target including any cancer cell surface antigen and second target including any T-cell antigen polypeptide, and the complex further comprises any masking moiety (MM1 and MM2) that inhibits the binding of the first and second antigen binding regions to their respective targets when the activatable complex is in an uncleaved state. Moreover, claim 31 recites that the MM1 and MM2 is a polypeptide comprises between about 5 amino acids to about 40 amino acids.
25. Given the exceedingly large genus of polypeptides of 5-40 amino acids in length, one of skill in the art cannot possibly envision which MM1 and MM2 structures contained within this genus will be capable of masking the binding of the first and second antigen binding regions to any target antigen. While the specification discloses a number of peptide-based masking moieties that are capable of inhibiting the binding of particular antibodies to their cognate epitopes (See Tables 5A and 5B, for example), these examples are not representative of the unlimited breadth of the claimed invention which includes any peptide with 5-40 amino acid residues.
26. Moreover, the first and second antigen binding regions (antibodies) recited in the claims can bind to any two targets, or slightly more limited in scope, a first target that is any cancer cell surface antigen and a second target that is any T-cell antigen polypeptide. Table 1 of the specification provides several cancer cell antigens, and Table 2 provides a number of prior art antibodies directed to the T-cell antigen CD3. However, the knowledge of the antigen and a particular antibody that binds the antigen does not direct a skilled artisan as to the necessary structure of an MM1 and MM2 that would be capable of inhibiting the binding of the antibody to the antigen. The art teaches that despite the growing knowledge around antibody structures and protein-protein interactions, "specific structural information - on the antibody to be optimized, its antigen and their interaction - is rarely available or lacks the high resolution required to determine accurately important details such as side-chain conformations, hydrogen-bonding patterns and the position of water molecules (Dufner et al. Trends Biotechnol 24(11): 523-529, 2006; see page 527, right column). Thus a skilled artisan would not be able to predict the structural requirements needed for the recited MM1 and MM2 to mask the binding of any antibody to its cognate antigen. While the Specification provides adequate written description for particular MM1 and MM2 masking moieties that mask the binding of a complex comprising an EGFR antigen binding domain and a CD3 binding domain, it does not provide adequate written description for the genus of MM1 and MM2 recited in the claims.
27. Furthermore, while the Specification provides adequate written description for particular antibodies that bind the tumor antigen EGFR and particular antibodies that bind the T-cell antigen CD3, it does not provide adequate written description for the genus of first and second targeting domains, which the Specification discloses may comprise any of the VL CDRs and VH CDRs listed in Table 2 (See pg. 24), that have the recited functions. Accordingly, the specification does not provide adequate written description of the claimed genus.
28. While generically the structure of antibodies is known, the structure of the presently recited antibodies to be produced and screened can vary substantially. As noted in Amgen, knowledge that an antibody binds to a particular epitope on an antigen tells one nothing at all about the structure of the antibody, wherein “instead of analogizing the antibody-antigen relationship to a ‘key in a lock,’ it [is] more apt to analogize it to a lock and ‘a ring with a million keys on it.” (Internal citations omitted). Therefore, those of skill in the art would not accept that the inventor had been in possession of the full genus of first and second targeting domains recited in the claims.
29. Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Abbvie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (759 F.3d 1285 (Fed. Cir. 2014). “When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus." Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005).
30. An adequate written description of a chemical invention requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that “[w]ithout such disclosure, the claimed methods cannot be said to have been described.”). See MPEP 2163IIA3(a).
31. Consequently, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus of any MM1 and MM2 capable of masking the binding of any first and second targeting domain, respectively, to any T-cell antigen and any tumor cell antigen encompassed in the breadth of the instant claims.
32. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that in order to satisfy the written description requirement, “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed structure of the encompassed genus of bispecific polypeptide complexes comprising an MM1 and MM2 capable of masking the binding of any first and second targeting domain, respectively, to any T-cell antigen and any tumor cell antigen, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
33. Without a correlation between structure and function, the claims do little more than define the claimed invention by function, which is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 ("definition by function does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is").
Claim Rejections - 35 USC § 103
34. 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 (i.e., changing from AIA to pre-AIA ) 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.
35. 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.
36. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
37. 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.
38. Claims 1-11, 14-20, 22, 24-26, 29-31, 35-38, 49 and 51-54 is/are rejected under 35 U.S.C. 103 as being obvious over Boustany et al. (WO 2019/075405; published 2019; cited by Applicant) in view of Bernett et al. (WO 2018/045110; published 2019; cited by Applicant), Xenaki et al. (Front. Immunol.8:1287, published 2017), and Rayner et al. (J Biol Chem. 290(13):8420-8438; published 2015).
39. Boustany teaches an activatable anti-EGFR, anti-CD3 heteromultimeric bispecific polypeptide complex (HBPC) (FIG. 17; FIG. 18 'CI107', and FIG. 19 'CI106') an anti-EGFR IgG antibody (divalent double-armed) that binds to first target (AB1; c225v5 - details in Table 6) with each light chain linked to masking moiety (MM) and cleavable moiety (CM) (CM1-MM1) and each heavy chain linked respectively to C- terminus of anti-CD3 scFv that bind second target (AB2; v16 - details in Table 1) with N-terminal MM-CM construct (CM2-MM2). Boustany further teaches antibodies or antigen binding fragments specific for CD3 epsilon (¶ [0063]). Within HBPC CI106 as taught by Boustany, CM1 contains serine protease substrate "LSGRSDDH" and CM2 contains a substrate "ISSGLLSGRSDQH" that can be cleaved by both the same serine protease and a different protease (e.g. MMP14) as evidenced by Moore (column 4; column 179; column 186. Such proteases are further disclosed to be elevated within the tumor microenvironment. Boustany further teaches that the bispecific antibody can be incorporated into pharmaceutical compositions which comprise a pharmaceutically acceptable carrier (¶ [0216]- [0217]), utilized within kits (¶ [0240]-[0245]). Boustany also teaches the HBPC reduces human xenograft tumor growth in mouse models (Figures 4-5), suggesting HBPC effectiveness of treating cancer in humans.
40. Boustany et al. does not teach a one-arm scFv-mAb.
41. Bernett et al. teaches a one armed scFv-mAb (Figure 2D) wherein one monomer comprises just an Fc domain, another monomer comprises an scFv attached to the N-terminus of the heavy chain such that the format from N- to C-terminus is as follows: VH1- scFv linker-VL1-[optional linker]-VH2-CH1-hinge-CH2-CH3 or (in the opposite orientation) VL1- scFv-linker-VH1-[optional linker]-VH2-CH1-hinge-CH2-CH3, and third monomer encodes an additional variable light chain and constant light domain that associates with the heavy chain to form a Fab (¶ [00443]).
42. Moreover, Xenaki et al. teaches engineering smaller antibody fragments has been shown to improve the rate of tumor uptake and intratumoral distribution (abstract), but smaller antibody fragments (i.e. scFvs) exhibit shorter plasma half-lives because of their inability to bind FcRn (i.e. through intact IgG Fc domain) (page 4, column 2, I 1). One of ordinary skill in the art would recognize bispecific antibodies can be constructed in various formats depending on binding requirements and tumor characteristics. Therefore, one of ordinary skill in the art would recognize that the symmetrical anti-EGFR, anti-CD3 heteromultimeric bispecific polypeptide complex (HBPC) as taught by Boustany can be substituted for a non-symmetric single arm format as taught by Bernett and would be motivated to do so because Xenaki teaches that smaller constructs with intact IgG Fc domain would likely have better intratumoral penetration while maintaining longer circulatory half-life. Bernett further teaches that for single-arm embodiments that comprise an Fc-only chain, this sequence comprises a format of hinge-CH2-CH3 (i.e. hinge-Fc2) ("Fc-only" fragments; Figure 68) and matching Fab-Fc HC fragment.
43. None of the teachings of Boustany, Bernett, and Xenaki teach different amino acid sequences for respective hinge domains (i.e. hinge sequence for Fc1 is different from hinge sequence for Fc2). However Rayner teaches the hinge domain as a three-part structure: (1) the upper hinge, which determines arrangement of the two Fab regions and mediates flexibility and reorientations of each Fab arm, (2) the middle hinge (or core) wherein two cysteine residues (Cys²²⁶ and Cys²²⁹) form interchain disulfide bonds between respective Fc pair, and (3) the lower hinge responsible for the flexibility and positioning of the Fc region and interactions with Fc receptors. One of ordinary skill in the art would recognize that in a polypeptide of Fc only domain (i.e. the third polypeptide of the instant HBPC), that an upper hinge domain would likely be superfluous, and that so long as the hinge core and lower hinge remain intact proper interactions with partner hinge would be possible. Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention that Fc domains on a single arm activatable scFv-mAb as taught by the combined teachings of Boustany, Bernett, and Xenaki could be designed such that the Fc only domain comprises a different hinge sequence (i.e. without an upper domain) since it does not comprise an immunoglobin variable domain because Rayner teaches the core and lower hinge domains are responsible for Fc domain interactions. A person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (see KSA International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQe2d 1385 (2007)).
44. Accordingly, the invention, taken as a whole, is prima facie obvious over the combined teachings of the prior art.
Double Patenting
45. 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 claims at issue 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); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
46. 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
47. The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
48. Claims 1-11, 14-20, 22, 24-26, 29-31, 35-38, 49 and 51-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14, 18-20, 23-33, 36-41, 44, 47-50 and 52-56 of U.S. Application No. 18/046,855 (reference application). The reference application is not afforded safe harbor protection under 35 USC 121 because the claims do not share continuity nor a restriction/speciation with the claims of the instant application. See Pfizer Inc. v. Teva Pharmaceuticals USA Inc., 86 USPQ2d 1001 (Fed. Cir. 2008).
49. Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of the reference application are drawn to a species of activatable heteromultimeric bispecific polypeptide complexes that is encompassed the genus of heteromultimeric bispecific polypeptide complexes recited in the instant claims.. Therefor the instant claims are obvious over the claims of the ‘855 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
50. Claims 1-11, 14-20, 22, 24-26, 29-31, 35-38, 49 and 51-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Application No. 18/701,356 (reference application). The reference application is not afforded safe harbor protection under 35 USC 121 because the claims do not share continuity nor a restriction/speciation with the claims of the instant application. See Pfizer Inc. v. Teva Pharmaceuticals USA Inc., 86 USPQ2d 1001 (Fed. Cir. 2008).
51. Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of the reference application are drawn to a species of activatable heteromultimeric bispecific polypeptide complexes that is encompassed the genus of heteromultimeric bispecific polypeptide complexes recited in the instant claims.. Therefor the instant claims are obvious over the claims of the ‘356 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Summary
52. No claim is allowed.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JON M LOCKARD whose telephone number is (571) 272-2717. The examiner can normally be reached M-F 9-6 EST.
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, Joanne Hama can be reached on (571) 272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JON M LOCKARD/Examiner, Art Unit 1647 March 26, 2026
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