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. Applicant’s election without traverse of Group I and the species of E345R, E430G, and S440Y as well as SEQ ID NO:31 in the Response filed on January 5, 2026 is acknowledged.
Claims 1-76 have been canceled.
Claims 77-92 have been added.
Claims 90-92 have been withdrawn under 37 CFR 1.142(b) as being drawn to nonelected invention.
Claims 77-89 are currently under consideration as they read on the elected invention of a homodimeric stradomer unit comprising at least one homodimeric IgG1 Fc comprising two Fc monomers, each comprising a T299A, E345R, E430G, and S440Y substitutions and corresponding amino acid sequence of SEQ ID NO:32.
3. The instant specification is objected to for following informalities:
[00254]-[00255] in page 79 of the specification as-filed discloses “E340G”. This appears to be a typographic error because the instant specification discloses E430G substitution, not E340G. Appropriate correction is required.
4. The specification is further objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required:
Applicant is requested to identify the written support for claims 77-89, particularly the claimed limitations of “wherein the homodimeric stradomer unit preferentially forms a hexameric multimerized stradomer and demonstrates retained C1Q binding relative to a homodimeric stradomer unite that does not comprise the T299A point mutation and the point mutations of (a), (b), or (c)”. (a)-)c) each contains mutations listed below:
(a) E345R,
(b) E430G and S440Y, and
(c) E345R, E430G, and S440Y
Alternatively, applicant is invited to amend the specification to provide antecedent basis for the claimed subject matter.
5. Applicant claim for domestic benefit is acknowledged. However, the parent USSN 16/315,871 upon which priority is claimed fails to provide adequate support under 35 USC 112 first paragraph for claims 77-89. Specifically insufficient support was identified for the limitation of “wherein the homodimeric stradomer unit preferentially forms a hexameric multimerized stradomer and demonstrates retained C1Q binding relative to a homodimeric stradomer unite that does not comprise the T299A point mutation and the point mutations of (a), (b), or (c)”.
Consequently, the claims have been accorded the priority of the filing date of the instant application on January 31, 2023.
Should Applicant disagree with the Examiner’s factual determination above, it is incumbent upon Applicant to provide a showing that specifically supports the instant claim limitations.
6. 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 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.
7. 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.
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.
8. Claims 77-89 are rejected under 35 U.S.C. 103 as being unpatentable over Block et al. (WO/2012016073, reference on IDS) in view of Wittrup et al. (US 8,815,237, reference of record), Reye et al. (2012/0100140, reference on IDS), and Diebolder et al. (Science 2014 March 14; 343(6176):1260-1263, reference on IDS).
Block et al. teach stradomer units comprising IgG1 Fc domain and a multimerization domain (e.g. see [0014] in page 5). Block et al. teach that the multimerization domain is an IgG2 hinge region lined to the Fc domain (e.g. see [0023] in page 8).
Block et al. teach that the stradomer G045c (SEQ ID NO:4) exhibits increased binding to all Fc receptors including FcγRIIIa (e.g. see [00227] in page 77). Further, Block et al. teach that the homodimeric stradomer units can form higher orders, e.g. six homodimeric stradomer units via self-aggregation (e.g. see Figure 1h and [0064]-[0065]). Block et al. teach that the Fc domain can be mutated to improve the binding to FcγR (e.g. see pages 36-37).
Block’s SEQ ID NO:4 is 98.2% identical to instant SEQ ID NO:31 (see sequence alignment below)
RESULT 6
AZT01893
(NOTE: this sequence has 9 duplicates in the database searched)
ID AZT01893 standard; protein; 264 AA.
XX
AC AZT01893;
XX
DT 15-MAR-2012 (first entry)
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DE Inflammatory disease treatment related fusion protein G045c, SEQ ID 4.
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KW IgG1; IgG2; Immunoglobulin G1; Immunoglobulin G2; alzheimers disease;
KW anemia; antiallergic; antianemic; antiarthritic; antibacterial;
KW antidiabetic; antiinflammatory; antimicrobial-gen; antiparkinsonian;
KW antipsoriatic; arthritis; atopic dermatitis; autoimmune disease;
KW bacterial infection; celiac disease;
KW chronic inflammatory demyelinating polyneuropathy; dermatological;
KW endocrine-gen.; fusion protein; gastrointestinal-gen.;
KW genetic-disease-gen.; hashimotos disease; hematological-gen.;
KW huntingtons chorea; idiopathic thrombocytopenic purpura;
KW immune modulation; immunomodulator; immunosuppressive;
KW infectious disease; inflammatory bowel disease; inflammatory disease;
KW insulin dependent diabetes; kawasaki disease; metabolic-gen.;
KW multiple sclerosis; musculoskeletal-gen.; myasthenia gravis;
KW neuroprotective; nootropic; osteopathic; osteopenia; osteoporosis;
KW parkinsons disease; protein production; protein therapy; psoriasis;
KW recombinant protein; scleroderma; systemic lupus erythematosus;
KW therapeutic; uveitis; vasotropic; viral infection; virucide.
XX
OS Homo sapiens.
OS Synthetic.
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FH Key Location/Qualifiers
FT Peptide 1..20
FT /label= Signal_peptide
FT Domain 21..252
FT /label= Immunoglobulin_G1_Fc_domain
FT Domain 253..264
FT /label= Immunoglobulin_G2_multimerization_domain
XX
CC PN WO2012016073-A2.
XX
CC PD 02-FEB-2012.
XX
CC PF 28-JUL-2011; 2011WO-US045768.
XX
PR 28-JUL-2010; 2010US-0368465P.
XX
CC PA (GLIK-) GLIKNIK INC.
XX
CC PI Block DS, Olsen H;
XX
DR WPI; 2012-B54767/12.
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CC PT New stradomer unit useful for treating e.g. arthritis, and type I
CC PT diabetes comprises leader sequence, immunoglobulin G1 crystalline
CC PT fragment domain, and multimerization domain, where leader sequence is
CC PT directly linked to the domain.
XX
CC PS Claim 20; SEQ ID NO 4; 124pp; English.
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CC The present invention relates to a novel stradomer unit comprising a
CC leader sequence, an immunoglobulin G1 (IgG1) crystalline fragment (Fc)
CC domain and a multimerization domain, where the leader sequence is
CC directly linked to the IgG1 Fc domain, and the IgG1 Fc domain is directly
CC linked to the multimerization domain or the leader sequence is directly
CC linked to the multimerization domain and the multimerization domain is
CC directly linked to the IgG1 Fc domain. The invention also provides: a
CC stradomer composition comprising the stradomer units; a cluster stradomer
CC comprising the stradomer units; a method for modulating an immune
CC response in a subject; a method for treating inflammatory disease in a
CC subject; a method for blocking nonspecific binding of antibodies in an in
CC vitro or ex vivo assay; a method for reducing endotoxin levels in a
CC composition; and a method for producing a cluster stradomer. The
CC stradomer composition is useful for treating inflammatory disease in a
CC subject, where the inflammatory disease is an autoimmune disease selected
CC from arthritis, multiple sclerosis, type I diabetes, autoimmune
CC thyroiditis, idiopathic thrombocytopenic purpura, chronic inflammatory
CC demyelinating polyneuropathy, scleroderma, autoimmune uveitis, systemic
CC lupus erythematous, myasthenia gravis, atopic dermatitis, autoimmune
CC anemia, psoriasis, inflammatory bowel disease, celiac disease, Kawasaki
CC Disease, sickle cell crisis. It is also useful for treating Alzheimer's
CC disease, Parkinson's disease, Huntingdon's disease, osteopenia, and
CC osteoporosis. The inflammatory disease is an infectious disease such as
CC bacterial infection, or viral infection. The present sequence represents
CC an inflammatory disease treatment related fusion protein comprising a
CC leader sequence, an IgG1 Fc domain, and an IgG2 multimerization domain
CC used in the stradomer composition of the invention.
XX
SQ Sequence 264 AA;
Query Match 98.2%; Score 1429; Length 264;
Best Local Similarity 98.5%;
Matches 260; Conservative 0; Mismatches 4; Indels 0; Gaps 0;
Qy 1 METDTLLLWVLLLWVPGSTGEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 METDTLLLWVLLLWVPGSTGEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR 60
Qy 61 TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSAYRVVSVLTVLHQDWLN 120
||||||||||||||||||||||||||||||||||||||||||| ||||||||||||||||
Db 61 TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN 120
Qy 121 GKEYKCKVSNKALPAPIEKTISKAKGQPRRPQVYTLPPSREEMTKNQVSLTCLVKGFYPS 180
||||||||||||||||||||||||||||| ||||||||||||||||||||||||||||||
Db 121 GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPS 180
Qy 181 DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHGALHNH 240
|||||||||||||||||||||||||||||||||||||||||||||||||||||| |||||
Db 181 DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH 240
Qy 241 YTQKYLSLSPGKERKCCVECPPCP 264
|||| |||||||||||||||||||
Db 241 YTQKSLSLSPGKERKCCVECPPCP 264
Block’s IgG1 Fc is EEM polymorph since it has an amino acid D in position 356 and M at position 358.
The reference teachings differ from the instant invention by not describing amino acid substitution T299A, E345R, E430G, and S440Y.
Wittrup et al. (US 8,815,237) teach an antibody comprising amino acid substitution T299A wherein the antibody is aglycosylated but retain the binding to Fcγ receptors (e.g. see claim 17). Wittrup et al. further teach that the aglycosylatd antibody enables significantly less expensive microbial manufacture of therapeutic agent containing Fc region (e.g. see lines 23-29 in col. 4).
Reyes et al. teach stability-engineered Fc polypeptide by substituting the pre-existing amino acid residue T (threonine) at position 299 with A (alanine) (e.g. see [0019]). Reyes et al. teach that the stabilized Fc polypeptide has enhanced half-life and is dimeric (e.g. see [0043] and [0045]). Reyes et al. further teach IgG1 consisting T299A substitution exhibits reduced binding to C1q (e.g. see Fig. 9 and [0131]).
Diebolder et al. teach an Fc variant comprising amino acid substitutions E345R, E430G, and S440Y readily formed hexamers in solution and exhibits increased CDC relative to the parent unmutated Fc (e.g. see paragraph spanning pages 2-3).
It would thus be obvious to one of ordinary skill in the art at the time the instant invention was filed to combine the teachings of the references to produce a multimer comprising the stradomer unit with amino acid substitutions T299A, E345R, E430G, and S440Y for the stability and hexamer formation and increased binding to C1q.
An ordinary skill in the art would have been motivated to do so, and have a reasonable expectation of success, since Block teaches higher orders of stradomer can be mutated in the Fc region for improved binding to Fc receptor, and Wittrup et al. and Reyes et al. teach T299A substitution in the Fc region of human IgG1 improves stability but reduced binding to C1q. However, Diebolder et al. teach substitution E345R, E430G, and S440Y in the Fc region of human IgG1 can yield hexamer and improve binding to C1q. As such, an ordinary skill in the art would be able to modify the therapeutic stradomer units disclosed in Block et al. with known methods of amino acid substitutions in the Fc region to improve stability and improve binding to C1q or maintain C1Q binding as shown in Wittrup et al. and Reyes et al. and Diebolder et al.
Given that a compound cannot be separated from its properties, see In re Papesch, 315 F.2d 381,391 (CCPA 1963) (“a compound and all its properties are inseparable), the prior art compound having identical structures of the instantly claimed homodimeric stradomers (namely amino acid substitutions T299A, E345R, E430G, and S440Y) would inherently/intrinsically have the same properties as the instantly claimed homodimers including capable of multimerizing said homodimeric stradomer units, or exhibits retained or enhanced binding to FcγRI relative to a homodimeric stradomer of the same structure that does not comprise the T299A mutations as recited in instant claims 77-89.
9. No claim is allowed.
10. 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