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
Amendment Entry
1. Applicant’s response to the Non-Final Action dated 6/17/25 (reply filed 10/13/25) is acknowledged. In the amendment filed therein claims 1-19 were canceled without prejudice or disclaimer. Claim 20 was modified. While new claims 21-31 were added. Currently, claims 20-31 are pending and under consideration.
2. Rejections and/or objections of record not reiterated herein have been withdrawn.
NEW GROUNDS OF REJECTIONS NECESSITATED BY AMENDMENTS
Information Disclosure Statement
3. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other
Information submitted for consideration by the Office, and MPEP § 609 A(1) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the examiner on form PTO-892 or applicant on form PTO-1449 lists the references, they have not been considered. See references listed throughout the disclosure.
4. The information disclosure statement filed 9/3/25 has been considered as to the merits prior to Final Action on the Merits.
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.
Claim Rejections - 35 USC § 112
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.
6. Claims 20-31 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.
A. Claim 20 is vague and indefinite because the recited method does not include a conclusion step that relates the preamble to the method outcome. As claimed, the method is directed to “suppressing non-specific reactions in antigen-antibody reactions in a sample”. However, the only active step is to contact the sample with a modified IgG antibody. As a result the claims are indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor(s) regards as the invention. Please add a conclusion step that provides a nexus between the preamble and method steps in order to obviate this rejection. The claims should be rewritten in appropriate method claim formats. For example, the modified IgG antibody binds to a non-specific reactant to suppress said non-specific reactions. Appropriate correction is required.
B. Claims 21 and 31 are 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. Claims 21 and 31 refer to a “non-specific reaction factor(s)”. However, claim 20 does not include the term factor(s). It is suggested that consistent claims language is utilized in order to eliminate inconsistencies. 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.
C. Claim 22 is vague and indefinite because it is not clear as to Applicant’s intended interpretation of “at least equivalent to” language. In other words it is not clear what the claim will encompass. Does equivalence refer to the same or higher binding specificity? Is the claim to be interpreted to read on the use of the same antigen with CH3 deleted in comparison to when CH3 is included? Or does the claim refer to some other comparative parameter (pH, KD, fluorescence, concentration, Response Time(RUI), etc.). In order to obviate the rejection, please clarify the intended parameter in the claim. Appropriate correction is required.
D. The term “reagent” in claims 26 and 27 is a relative term which renders the claims indefinite. The term “reagent” is not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
While sections 0010 and 0019 describe possible embodiments, the scope is too massive to define the terms; especially with respect to diagnostic and research. It is not clear as to how the reagent will be determined to be or considered a diagnostic reagent or a research reagent. The claim wording does not clearly set forth the intended reagent/composition that will be required in the method. It is suggested that the actual solution or reagent is added to the claims in order to remove ambiguity. Please clarify.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(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.
7. Claims 20 and 22-31 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.
Claims 20 and 22-31 are directed to a method of “suppressing non-specific reactions in antigen-antibody reactions in a sample, the method comprising contacting the sample with using an antibody comprising a fragment crystallizable (Fc) region that lacks a constant region heavy chain domain 3 (CH3), wherein the antibody is an Immunoglobulin G (IgG) antibody, and wherein 0 to 20 amino acids are inserted into or deleted from the C-terminal end of constant region heavy chain domain 2 (CH2).
The written description in this case does not set forth the possession or utility of a method that suppresses any and all non-specific reactions in the sample-antibody method as claimed.
Therefore the written description does not reasonably convey the claimed subject matter to one of ordinary skill in the art. Neither the specification nor the claims exemplify "all possible non-specific reactions that are involved in the sample-antibody method. There is no guidance as to what non-specific reactions are intended or how the interaction of the sample/antibody will allow for the measurement of the non-specific reactions. There is no indication as to how much modification can occur while maintaining product (modified IgG antibody) characteristics with respect to the instant invention.
There is no guidance as to what "portion of the modified IgG antibody” is required and can be produced and utilized for the intended purpose (suppressing any and all non-specific reactions). The specification does not include structural examples of every possible IgG binding antibody lacking CH3 having utility in the claimed method.
Thus, the resulting "modified IgG antibody reagent as claimed” having the intended specified binding characteristics could result in any number of complexes not taught and enabled by the specification.
Vas-Cath Inc. V. Mahurkar, 19 USPQ2d 1111, clearly states that "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). Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 USC 112 is severable from its enablement provision (see page 115).
Without a sequence or examples of " all IgG antibodies lacking CH3” including the necessary conserved binding areas, the skilled artisan cannot envision the detailed structure of the antibodies need to suppress any and all non-specific reactions.
Applicant does not provide guidance for the above noted IgG antibodies in the claimed method and provides no guidance as to what modifications or structure are important for the predictable function of the antibodies. Very different structures may be found on antibodies with the same specificity.
For example, very different VH chains can combine with the same VL chain to produce antibody binding sites with nearly the same size, shape, antigen specificity, and affinity. A similar phenomenon can also occur when different VH sequences combine with different VL sequences to produce antibodies with very similar properties.
These observations indicate that divergent variable region sequences, both in and out of complementarily determining regions, can be folded to form similar binding site contours, which result in similar immunochemical characteristics. Conversely, similar structure may be found on antibodies having different specificities.
Thus conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of production and or isolation.
An adequate description requires more than a mere statement that it is part of the invention and a reference to a potential method of isolating it.
The court indicated that while Applicants are not required to disclose every species encompassed by a genus, the description of a genus is achieved by the recitation of a representative number of molecules falling within the scope of the claimed genus. Therefore the full breadth of the claims, reading on the claimed suppression of "any and all non-specific reactions” when a sample interacts with a modified IgG antibody lacking CH3 does not meet the written description provision of 35 USC 112, first paragraph.
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.
8. Claim(s) 21-27 and 31 is/are rejected under 35 U.S.C. 103 as being unpatentable over 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).
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.
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.
9. Claim(s) 28-30 is/are rejected under 35 U.S.C. 103 as being unpatentable over 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 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.
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 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
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.
It is noted that a composition and its properties are inseparable. Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id. (Applicant argued that the claimed composition was a pressure sensitive adhesive containing a tacky polymer while the product of the reference was hard and abrasion resistant. "The Board correctly found that the virtual identity of monomers and procedures sufficed to support a prima facie case of unpatentability of Spada’s polymer latexes for lack of novelty."). See MPEP 2112.01.
Since Ramasamy et al., Miyafusa et al., and Sarmay et al. describe IgG antibodies with a deleted CH3 domain having binding interactions with antigens, it necessarily flows that the interaction would suppress non-specific reactions as claimed.
10. For reasons aforementioned, no claims are allowed.
11. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
12. 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 schedule but can normally be reached on Monday-Friday from 9am to 5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached on 571-270-3503. 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 1642
Hoteling
1/24/26
/LISA V COOK/Primary Examiner, Art Unit 1642