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 .
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 05/14/2026 is acknowledged. Applicant has further canceled claims corresponding to the requirement of a species election. Applicant’s further note- to the extent that the Examiner may believe an election of species is still required with regard to the claimed antigen binding polypeptide complex, Applicant elects an antigen binding polypeptide complex comprising a first polypeptide having a structure represented by VL1- L1-VL2-L2-VH2-L3-VH1-L4-Fc and a second polypeptide having a structure represented by VL3- L5-VL4-L6-VH4-L7-VH3-L8-Fc as recited in claim 128. Claims 128, 131-133, 137, 140-142 and 147 read on this species within Group I. The species chosen by applicant is accepted.
Claims 128, 131-133, 137, 140-142, 147, and 149-150 are pending.
Claims 149-450 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/14/2026.
Claims 128, 131-133, 137, 140-142 and 147 are pending and are currently under consideration.
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.
Claims 128, 131-133, 137, 140-142 and 147 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. This is a Written Description rejection.
Claim 128 and dependents thereof are broadly drawn to an “antigen binding polypeptide complex” comprising a first and second polypeptide wherein the first polypeptide has a general structure selected from:
VL1-VL2-VH2-VH1-Fc;
VH1-VH2-VL2-VL1-Fc;
VL1-L1-VL2-L2-VH2-L3-VH1-Fc;
VH1-L1-VH2-L2-VL2-L3-VL1-Fc;
VL1-L1-VL2-L2-VH2-L3-VH1-L4-Fc; or
VH1-L1-VH2-L2-VL2-L3-VL1-L4-Fc;
And the second polypeptide has a general structure selected from:
VL3-VL4-VH4-VH3-Fc;
VH3-VH4-VL4-VL3-Fc;
VL3-L5-VL4-L6-VH4-L7-VH3-Fc;
VH3-L5-VH4-L6-VL4-L7-VL3-Fc;
VL3-L5-VL4-L6-VH4-L7-VH3-L8-Fc; or
VH3-L5-VH4-L6-VL4-L7-VL3-L8-Fc.
Wherein the VLs represent any variable light chain regions and the VHs represent any variable heavy chain regions. Fc is a region comprising a heavy chain constant region 2 and heavy chain constant region 3 with an optional hinge domain and the L’s represent linker regions. The claims are further inclusive of pharmaceutical compositions comprising said antigen binding polypeptide complexes.
Thus, the claims encompass a large genus of extremely diverse polypeptide domains with the function of binding to any number of antigens. For example, the specification teaches [0152] that the recited multispecific and multivalent antibody constructs have embedded sequences that target and bind to epitopes on viral peptides such as but not limited to influenza virus neuraminidase, influenza virus hemagglutinin, human respiratory syncytial virus (RSV)-viral proteins, RSV F glycoprotein, RSV G glycoprotein, herpes simplex virus (HSV) viral proteins, herpes simplex virus glycoproteins gB, gC, gD and gE, Chlamydia MOMP and PorB antigens, core protein, matrix protein or other protein of Dengue virus, measles virus hemagglutinin, and herpes simplex virus type 2 glycoprotein gB. Or, such complexes could bind to [0153] a wide variety of antigens such as but not limited to CCL8, CCL11, CCL15, CCL17, CCL19, CCL20, CCL21, CCL25 CCR3, CCR4, CD3, CD16A, CD19, CD20, CD24, CD27, CD28, CD30, CD38, CD39, CD40, CD40L, CD47, CD52, CD70, CD80, CD86, CD123, CD133, CD137, CD137L, CD160, CD272, CEACAM5, CLEC9, CLEC91, CRTH2, CSF-1, CSF-2, CSF-3, CXCL1, CXCL2, CXCL4, CXCL12, CXCL13, CXCR3, cMet, CTLA4, DLL3, DLL4, DNGR-1, E-cadherin, EGFR, ENTPD1, EpCAM, FCER1, FCER1A, FCER2, FGFR, FLAP, FOLH1, Gi24, GITR, GITRL, GPR5, GP100, GPRC5D, HER2, or HER3. The diversity is of high concern because the variable regions of the claimed heavy and light chains currently comprise an extremely large genus of undefined complementary determining regions (CDRs). Moreover, the specification does not provide an adequate representative description for the entire claimed genus as one skilled in the art would be unable to envision, recognize, or distinguish which light and heavy chain CDRs and/or combination of CDRs are comprised within the claimed generic structures. Thus, as further detailed below, applicant’s disclosure does not satisfy the written description requirement of 35 U.S.C. 112(a).
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A “representative number of species” means that the species which are adequately 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. In the instant case, Applicant appears to have disclosed some members of the genus such as tetravalent, bispecific antibody (MX846) that binds to CD3 and CD20, a tetravalent, trispecific antibody configuration (MX855), that binds to CD3, CD28, and CD20. Other species include MX851 and MX853 (tetraspecific for CD3, CD28, BCMA, and to CD20; however, given the substantial antibody structure variation within the genus, as well as the high level of unpredictability in the art, the disclosure of a few species comprised within the claimed genus is not sufficiently representative of the entire genus.
It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. Further, the specification teaches [0091] that each VH and VL comprises three CDRs and four framework regions (FRs), arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. For example, Vajdos et al. (2002; PTO-892) teach that antigen binding is primarily mediated by the CDRs and that the more highly conserved framework segments which connect the CDRs are mainly involved in supporting the CDR loop conformations although in some cases framework residues also contact the antigen (page 416, left col.). Thus, even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function. Further, Chiu et al. (Antibodies 2019 8(4);55, 1-80) taught the antigen binding of antibodies often results in conformational changes in the contact surface areas of both the antibody and the antigen (page 5, first paragraph). Thus, the prediction of CDR binding to the epitope is difficult to predict. Chiu further taught antibody modeling has been shown to be accurate for the framework region sequences, but CDR modeling requires further development and improvements (page 6, second paragraph). Prediction of the structure of HCDR3 could not be accurately produced when given the Fv structures without their CDR-H3s (page 6, second paragraph). Chiu taught the quality of antibody structure prediction, particularly regarding CDR-H3, remains inadequate, and the results of antibody–antigen docking are also disappointing (page 11, paragraph 2). Thus, in view of Vajdos et al. and Chiu et al., it is apparent that antibodies having less than all six CDRs that form the antigen binding site of a conventional antibody in their proper context of heavy and light chain variable domains do not describe the particularly identifying structural feature of the antibody that correlates with the antibody's ability to bind antigen. Absent a description of at least minimal structural features correlating with a functional ability to bind an antigen which are shared by members of the genus commonly sharing this function, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish which heavy and light chain CDR amino acid sequences (or combinations thereof) may be combined such that the resultant heavy and light chain variable regions comprise six CDRs that confer the ability to bind an antigen.
Although screening techniques can be used to isolate sets of six heavy and light chain CDRs that possess the ability to bind an antigen, Applicant is reminded that the written description requirement of 35 U.S.C. 112 is severable from the enablement provision. As stated in Vas-Cath Inc. V. Mahurkar (CA FC) 19 USPQ2d 1111, 935 F2d 1555, "The purpose of the 'written description' requirement is broader than to merely explain how to 'make and use'; the applicant must also 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."
Accordingly given the unpredictability associated with antibody CDR region changes on antigen binding and given the lack of particularity with which the claimed antibodies are described in the specification, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish at least most of the members of the genus to which the claims are directed, and therefore the specification would not reasonably convey to the skilled artisan that Applicant was in possession of the claimed invention at the time the application was filed.
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.
Claims 128, 131-133, 137, 140-142 and 147 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 84-97, 98-99 of copending Application No. 18696493 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because Claim 84 of the reference application is drawn to a species of the larger genus represented by the current application. For example, Claim 84 includes first and second polypeptides (boxed) that are also claimed in the current application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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While the instant application does not specifically claim that each variable region binds to an HIV protein, the specification teaches [0136] that viral peptides from HIV are encompassed by the genus. The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim. In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02.
Similar to the above analysis, claims 128, 131-133, 137, 140-142 and 147 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 7-8, 17-18, 28, 32-34, 48, 52, and 66 of copending Application No. 18345478 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because Claim 7 of the reference application is drawn to a species of the larger genus represented by the current application. For example, Claim 7 includes first and second polypeptides (boxed) that are also claimed in the current application. The linker regions are generic to any linker.
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While the instant application does not specifically claim that each variable region binds to a SARS-CoV-2 protein, the specification teaches [0212, 0441] that viral peptides from SARS are encompassed by the genus. The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim. In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02.
Similar to the above analysis, claims 128, 131-133, 137, 140-142 and 147 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 76-79, 84-86 of copending Application No. 18069529 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because Claim 76 of the reference application is drawn to a species of the larger genus represented by the current application. For example, Claim 76 includes first and second polypeptides (boxed) that are also claimed in the current application. The linker regions are generic to any linker.
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While the instant application does not specifically claim that each variable region binds to a tumor associated antigens, the specification teaches [0069, 0153] that tumor associated antigens may be encompassed by the genus. This includes cMET, TROP2, and CD28. The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim. In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02.
The above rejections are provisional nonstatutory double patenting rejections because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu 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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/GARY B NICKOL/Primary Examiner, Art Unit 1643
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