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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicants’ submission filed on 5/27/26 has been entered.
Amendment Entry
3. Applicant’s response to the Final Action dated 1/27/26 (reply filed 5/27/26) is acknowledged. In the amendment filed therein claims 1-19, 22, and 26-27 were canceled without prejudice or disclaimer. Claims 20, 21, and 31 were modified. While new claim 32 was added. Currently, claims 20, 21, 23, 24, 25, 28, 29, 30, 31, and 32 are pending and under consideration.
4. Rejections and/or objections of record not reiterated herein have been withdrawn.
Priority
5. This application has a priority date of 3/26/20: This application is the U.S. National Stage of PCT/JP2021/012724, filed March 25, 2021, which claims priority to JP 2020-056081, filed March 26, 2020.
NEW GROUNDS OF REJECTIONS NECESSITATED BY AMENDMENTS
Claim Rejections - 35 USC § 103
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.
6. Claim(s) 20, 21, 23-25, 31, and 32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gabriel and Agnello (J. Clin. Invest. May 1977, 59(5), 990-1001) in view of Ramasamy et al. (Nature, London United Kingdom, 1975, 253, (5493), 656 CODEN) and Miyafusa et al. (WO 2019/172401 A1) and further in view of Sarmay et al. (Immunology Letters, Vol.12, Issue 5-6, June 1986, pages 307-312).
Gabriel and Agnello (J. Clin. Invest. May 1977, 59(5), 990-1001) disclose immunoassay procedures to measure IgG in a sample. This study describes two sensitive, rapid, relatively simple, competitive inhibition radio immunoassays for detecting immune complex. The tests are based on the inhibition of 125-Clq or I25-monoclonal rheumatoid factor (mRF) binding to an insoluble substrate, IgG-Sepharose. The assays can be performed in 5 h utilizing 10µul of serum. Heating of serum is not required and polyclonal rheumatoid factors do not interfere. With the two assays, a wide range of complexes of various size and complement fixing activity can be detected. See abstract and Radio-immunoassays. pages 991-992.
Gabriel and Agnello differ from the instant invention in not specifically teaching mutations in the CH2 and CH3 of IgG.
However, Ramasamy et al. discloses that membrane receptors recognizing the Fc portion of immunoglobulin molecules (Fc receptors) are found in many cells of the immune system. Fc receptors on lymphocytes are readily detected by a rosette test and this reaction is inhibited by pretreatment of the lymphocytes with IgG. IgG proteins lacking almost the entire CH1 and CH3 homology regions have been obtained from mutant cell lines of MOPC 21, a plasmacytoma secreting IgG1 and the extent of the deletions determined (Fig. 1). To identify that part of the IgG molecule which interacts with the Fc receptor, the researchers tested the ability of these IgG proteins to inhibit Fc rosette formation on murine lymph node cells. The data demonstrated (Table 1) that an intact CH3 region is essential for the binding of IgG to Fc receptors on lymph node cells. See abstract.
While, Miyafusa et al. disclose a C-terminal deleted CH3 domain comprising (a) an amino acid sequence in which an amino acid is deleted within 5-20 residues from the C-terminal side in an amino acid sequence of SEQ ID NOs: 1-7, or (b) an amino acid sequence in which an amino acid is deleted within 5-20 residues from the C-terminal side in an amino acid sequence in which one or several amino acids in an amino acid sequence of SEQ ID NOs: 1-7 is substituted, deleted, inserted, and/or added, is new, where the C-terminal deleted CH3 domain specifically binds to AF.2A1 polypeptide. See abstract.
Miyafusa et al. recite claims comprising: fragment crystallizable (Fc) region fragment, antibody or protein comprising the C-terminal deleted CH3 domain; evaluation kit comprising at least one chosen from the C-terminal deleted CH3 domain, Fc region fragment, antibody or protein; method for quantitatively measuring a denatured antibody contained in a sample, involves (a) measuring the binding amount between the AF.2A1 polypeptide and denatured antibody, (b) measuring the binding amount between the AF.2A1 polypeptide and the C-terminal deleted CH3 domain, Fc region fragment, antibody or protein and calculating the amount of denatured antibody from the binding amount between the C-terminal deleted CH3 domain, the Fc region fragment, the antibody or the protein and AF.2A1 polypeptide; method for screening a compound having affinity for a denatured antibody, involves measuring the interaction between the C-terminal deleted CH3 domain, Fc region fragment, antibody or protein and test compound; and reference reagent comprising C-terminal deleted CH3 domain, Fc region fragment, antibody or the protein as reference substances. See Description.
With respect to the insertion or deletion of 0-5 amino acids in the c-terminal of CH2, it is noted that zero amino acid modifications read on the inclusion of native CH2 (without any changes). Absent evidence to the contrary, since IgG necessarily comprises CH2 and CH3; the CH2 portion is comprised in the teachings of Ramasamy et al. and Miyafusa et al.
It would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of applicant’s invention to modify the CH2 and/or CH3 domain from an IgG antibody as exemplified by Ramasamy et al. and Miyafusa et al. in the assays of Gabriel and Agnello in order to eliminate interferants previously taught by the prior art without heating because heating could damage the reagents and cause erroneous results. See Gabriel and Agnello pages 992-999.
Gabriel and Agnello, Ramasamy et al. and Miyafusa et al. differ from the instant invention in not specifically teaching the removal or deletion of the entire CH3 region and the importance of the deleted CH3 region in IgG antibody-antigen binding.
However, Sarmay et al. disclose that domain deleted paraproteins are suitable tools to study the interaction between IgG domains and Fc receptor (FcR) binding sites (antigens). The effect of the Cγ2 or Cγ3 domain deleted paraproteins was compared on antibody dependent cellular cytotoxicity (ADCC) and on FcR mediated rosette formation.
The Cγ2 domain deleted paraprotein (TIM) had no significant effect on lymphocyte or monocyte mediated ADCC, while the Cγ3 domain deleted paraprotein (SIZ) inhibited both types of cytotoxicity. FcR dependent rosette formation was also inhibited by SIZ but TIM was ineffective.
The data further confirm a significant role of Cγ2 domain in the transfer of killing signal in ADCC and that of Cγ3 domain in the high affinity binding to lymphocyte FCR. See abstract.
It would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of applicant’s invention to delete the entire CH3 domain from an IgG antibody in order to inhibit ADCC cytotoxicity and FcR dependent rosette formation in IgG binding complexes. See Sarmay et al. abstract.
One skill in the art would have been motivated to eliminate cytotoxicity to eliminate negative binding interactions that could be detrimental to cell interactions.
7. Claim(s) 28-30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gabriel and Agnello (J. Clin. Invest. May 1977, 59(5), 990-1001) in view of Ramasamy et al. (Nature, London United Kingdom, 1975, 253, (5493), 656 CODEN) and Miyafusa et al. (WO 2019/172401 A1) in view of Sarmay et al. (Immunology Letters, Vol.12, Issue 5-6, June 1986, pages 307-312) and further in view of Maggio (Immunoenzyme technique I, CRC press [Symbol font/0xE3] 1980, pages 186-187).
Please see Gabriel and Agnello (J. Clin. Invest. May 1977, 59(5), 990-1001), Ramasamy et al. (Nature, London United Kingdom, 1975, 253, (5493), 656 CODEN) and Miyafusa et al. (WO 2019/172401 A1) in view of Sarmay et al. (Immunology Letters, Vol.12, Issue 5-6, June 1986, pages 307-312) as set forth above.
Gabriel and Agnello (J. Clin. Invest. May 1977, 59(5), 990-1001), Ramasamy et al. (Nature, London United Kingdom, 1975, 253, (5493), 656 CODEN) and Miyafusa et al. (WO 2019/172401 A1) in view of Sarmay et al. (Immunology Letters, Vol.12, Issue 5-6, June 1986, pages 307-312) do not teach that the biomarkers are coupled to a solid support.
However, Maggio teaches assay procedures wherein either the antigen or antibody is immobilized onto a solid phase. The solid phase can be particles, cellulose, polyacrylamide, agarose, discs, tubes, beads, or micro plates (micro titer plates). See page 186. The reagents can be bound to the solid support by covalent linkage or passive adsorption (non-covalent means). See page 187 1st paragraph. Maggio taught that solid supports such as test strips “are very convenient to wash thereby reducing labor in assay procedures”. Page 186, last line.
KSR forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See recent Board decision Ex parte Smith,--USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007)(citing KSR, 82 USPQ2d at 1396).
Therefore, it would have been obvious to one of ordinary skill in the art at the effective filing date of the invention to utilize solid support configured to attach the antibodies taught by Gabriel and Agnello (J. Clin. Invest. May 1977, 59(5), 990-1001), Ramasamy et al. (Nature, London United Kingdom, 1975, 253, (5493), 656 CODEN) and Miyafusa et al. (WO 2019/172401 A1) in view of Sarmay et al. (Immunology Letters, Vol.12, Issue 5-6, June 1986, pages 307-312) onto carriers because Maggio taught that reagents can be immobilized onto known carrier compositions like nitrocellulose or polyvinylidene fluoride which are deemed to encompass obvious modifications of the substrates known in the art for use in microplates since it has been held that the provision of adjustability, where needed, involves only routine skill in the art. In re Stevens, 101 USPQ 284 (CCPA 1954).
Response to Arguments
8. Applicant argues that Ramasamy describes Fc receptor binding and rosette inhibition and concludes that an intact Cγ₃ region is essential for binding of IgG to Fc receptors on lymph node cells. Sarmay similarly concerns the role of Cγ2 and Cγ₃ domains in antibody dependent cellular cytotoxicity (ADCC) and Fc receptor-mediated rosette formation. Thus, both Ramasamy and Sarmay describe Fc receptor interactions in immune cell contexts. By contrast, the present claims are specifically directed to suppressing non-specific reactions caused by binding of C1q and/or rheumatoid factor present in a sample to the Fc region. Neither Ramasamy nor Sarmay teaches or suggests suppression of non-specific reactions caused by C1q binding or rheumatoid factor binding in a sample. Nor do those references teach or suggest that deletion of CH3 in an lgG antibody would suppress non-specific reactions. This argument was carefully considered but was not found persuasive in view of the reference to Gabriel and Agnello (J. Clin. Invest. May 1977, 59(5), 990-1001).
Applicant contends that Ramasamy et al. and Miyafusa et al. do not anticipate a method that employs a 'FC-deleted' antibody, e.g. in which the deletion of a CH3 domain from the antibody is useful in suppressing non-specific reactions in antigen-antibody reactions. This argument was carefully considered and found persuasive. The reference to Sarmay et al. has been added to make the use of a CH3 deleted IgG useful in antibody-antigen reactions.
9. For reasons aforementioned, no claims are allowed.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LISA V COOK whose telephone number is (571)272-0816. The examiner works a flexible Part-Time schedule but can normally be reached on Monday, Thursday, and Friday from 9am to 5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached on 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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Lisa V. Cook
Patent Examiner
Art Unit 1641
Hoteling
9/5/26
/LISA V COOK/Primary Examiner, Art Unit 1641
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