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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3/15/2026 has been entered.
Withdrawn Claim Rejections
The 112(a) written description rejection and 102 rejection are hereby withdrawn in view of canceled claims.
Status of the Claims
Claims 17-20 are new and currently under prosecution.
New Rejections
(Necessitated by new claims)
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 17-20 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.
The claims are drawn to a method for treating fulminant myocarditis in a subject, comprising: administering an effective amount of an antibody to the subject; wherein the antibody is one of anti-sST2 neutralizing antibody and anti-CD163 neutralizing antibody. Thus, the claims disclose the antibodies by function only, to treat fulminant myocarditis. No structure of the antibodies is disclosed in the claims.
With regards to the claimed antibody, the instant specification discloses one experimental example of an anti-sST2 neutralizing antibody and an anti-CD163 neutralizing antibody that treats fulminant myocarditis as claimed. This is disclosed in experimental example 6 (Anti-sST2 neutralizing antibody can inhibit myocardial injury induced by CVB3 in A/J fulminant myocarditis mice) and experimental example 7 (Anti-CD163 neutralizing antibody can improve cardiac dysfunction in A/J fulminant myocarditis mice induced by CVB3). The specification fails to disclose any structural sequence required of a drug to possess the function of treating fulminant myocarditis.
By the time of the filing of the instant application, it was well established in the art that the formation of an intact antigen-binding site in an antibody usually required the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three “complementarity determining regions” (“CDRs”) which provide the majority of the contact residues for the binding of the antibody to its target epitope. E.g., Almagro & Fransson, Frontiers in Bioscience 2008; 13:1619-33; (see Section 3 “Antibody Structure and the Antigen Binding Site” and Figure 1). Humanized antibodies comprise only the CDRs, or in some cases an abbreviated subset of residues within the CDRs, of a parental rodent antibody in the context of human framework sequences. Id. at Section 4. All of the CDRs of the heavy and light chain, in their proper order of CDR1, then 2, then 3, and in the context of framework sequences which maintain their required conformation are generally required to produce a humanized antibody in which the heavy and light chains associate to form an antigen-binding region that binds the same antigen as the parental rodent antibody. Id. at Section 4.
Antibody binding to the same antigen, or even the same epitope on that antigen, can be accomplished with an impressively wide variety of antibody structures, even when the antibodies are limited to those from a particular source (Gershoni et al., Epitope Mapping, Biodrugs 2007; 21 (3): 145-156 page 146 section 1.1). The skilled artisan therefore understood that antibodies from a variety of different sources may bind the same antigen and even mediate the same functional effects, but differ widely in the details of the structure of their antigen-binding sites, particularly in the amino acid sequence and length of VH-CDR3.
Further, it is not possible to predict the amino acid sequence when an epitope is recited, because there are many different epitope arrangements, such as linear and discontinuous epitopes that is dictated by the unique interaction between an antibody and its cognate epitope (Blythe et al., Benchmarking B cell epitope prediction: Underperformance of existing methods, Protein Science (2005), 14:246–248 pg. 246) . 3D structural analyses of antibody-epitope binding highlighting that the deficiency in the ability to predict the structural features of an antibody when the epitope is disclosed (Schreiber et al.,3D-Epitope-Explorer (3DEX): Localization of Conformational Epitopes within Three-Dimensional Structures of Proteins, Wiley Interscience, 2005 42–44, 60596, page 879).
The structure activity relationship of the CDR antigen binding region that neutralizes sST2 or CD163 are not known and the binding epitopes cannot be predicted based on the antibody sequences. Kania G. (Soluble ST2 beyond a biomarker: a pathogenic driver and therapeutic target in fulminant myocarditis. Eur Heart J. 2026 Mar) teaches soluble growth stimulation-expressed gene 2 (Sst2) is a central pathogenic factor in FM and teaches that targeting sST2 with antibodies can be a promising therapeutic, however, there are long-term consequences of sST2 that need to be evaluated. [whole document] With regards to anti-CD163 antibodies, Etzerodt et al (CD163 and inflammation: biological, diagnostic, and therapeutic aspects. Antioxid Redox Signal. 2013 Jun 10;18(17):2352-63) teaches the role of CD163, and teaches the use of only one CD163-targeting therapy. [whole document] CD163 antibody are not known in the art.
To provide adequate written description and evidence of possession of the claimed antibody genus, the instant specification can structurally describe representative drugs that function as listed above or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.). A disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product.
Although Applicants may argue that it is possible to screen for targets that function as claimed and listed above, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,’ not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future drugs yet to be discovered that may function as claimed. The biomarker antigens provide no information about the structure of an antibody functions to treat fulminant myocarditis as recited above.
The instant specification fails to describe structural features common to the members of the genus, which features constitute a substantial portion of the genus because the instant specification does not disclose any structures/sequences that function as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the antibody does, rather than what it is. The specification fails to provide any structural features coupled to the claimed functional characteristics. The instant specification fails to describe a representative number of sequences for the genus of drugs that function as claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus required to perform the claimed method.
Given the lack of representative examples to support the full scope of the claimed antibody used in the claimed method, and lack of reasonable structure-function correlation for the antibody to function as listed above, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of antibodies that treat fulminant myocarditis that is required to practice the claimed invention. Since the specification fails to adequately describe the product to which the claimed method uses, it also fails to adequately describe the method.
Response to Relevant Arguments
Applicant argues that the specification provides explicit support for both embodiments and points to examples 6 and that discloses administration of anti-sST2 neutralizing antibody and CD163 neutralizing antibody, respectively. Applicant argues that these working examples demonstrate that the inventors were in full possession of the claimed therapeutic methods. Applicant argues that the instant application lies in the therapeutic use of sST2 use of sST2 and CD163 inhibition for treating fulminant myocarditis not the structure of the antibodies themselves, and that these antibodies are well known in the art.
Applicant’s arguments have been considered but are not persuasive.
Examiner points to MPEP 2163 II.A.3(a):
3. Determine Whether There is Sufficient Written Description to Inform a Skilled Artisan That Inventor was in Possession of the Claimed Invention as a Whole at the Time the Application Was Filed
An adequate written description of a chemical invention also 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.").
In this situation, the claims are drawn to a method of treating fulminant myocarditis, comprising administering an anti-sST2 neutralizing antibody or an anti-CD163 neutralizing antibody. The instant specification only discloses one antibody of each. There is a limited number of these antibodies, and they do not provide full scope of the genus of an anti-sST2 neutralizing antibodies or an anti-CD163 neutralizing antibodies. Thus, to provide support for the claimed method, there needs to be support for the products used therein.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 17 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hang et al (Fulminant myocarditis: a comprehensive review from etiology to treatments and outcomes. Signal Transduct Target Ther. 2020 Dec 11;5(1):287).
Hang teaches a method for treating fulminant myocarditis in a subject, comprising administering an effective amount of antibody to the subject, wherein the antibody is an anti-sST2 neutralizing antibody. Hang et al teaches fulminant myocarditis (FM) teaches that CD163 and sST2 and is increased in patients with FM. [figure 2] Hang teaches that sST2 was significantly increased when patients were admitted and decreased to normal levels as the patient improved. Hang teaches that in vivo experiments demonstrate that mice treated with sST2 had decreased heart function, while experimental FM mice showed better survival rates when treated with an anti- sST2 antibody. [pg 9, 2nd column]
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.
Claim(s) 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Hang et al (Fulminant myocarditis: a comprehensive review from etiology to treatments and outcomes. Signal Transduct Target Ther. 2020 Dec 11;5(1):287), in view of Al Shoyaib et al (Intraperitoneal Route of Drug Administration: Should it Be Used in Experimental Animal Studies? Pharm Res. 2019 Dec 23;37(1):12).
The teachings of Hang are recited above. However, Hang does not explicitly recite that the anti-sST2 antibody is administered intraperitoneally as recited in claim 18.
Al Shoyaib teaches known methods of using intraperitoneal administration with antibodies, especially in in vivo experiments. [whole document]
It is noted that claim(s) 18 requires that the anit-sST2 antibody is administered intraperitoneally. This limitation would have been obvious to those of ordinary skill in the art because: (1) Hang teaches the use of an anti-sST2 antibody for the treatment of fulminant myocarditis, (2) Hang demonstrates the use of this antibody in vivo, and (3) Al Shoyaib teaches known methods of administering drugs in vivo ¸including intraperitoneally.
Response to Relevant Arguments
Applicant argues that newly independent claim 17 achieves significant therapeutic benefits in fulminant myocarditis, including markedly improved survival, enhanced cardiac function and suppression of the pathogenic cytokine storm yielding unpredictable result.
Applicant’s arguments have been considered but are not persuasive. . With regards to unexpected results, the MPEP states:
MPEP 716.02(d) states: Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (Claims were directed to a process for removing corrosion at “elevated temperatures” using a certain ion exchange resin (with the exception of claim 8 which recited a temperature in excess of 100C). Appellant demonstrated unexpected results via comparative tests with the prior art ion exchange resin at 110C and 130C. The court affirmed the rejection of claims 1-7 and 9-10 because the term “elevated temperatures” encompassed temperatures as low as 60C where the prior art ion exchange resin was known to perform well. The rejection of claim 8, directed to a temperature in excess of 100C, was reversed.). See also In re Peterson, 315 F.3d 1325, 1329-31, 65 USPQ2d 1379, 1382-85 (Fed. Cir. 2003) (data showing improved alloy strength with the addition of 2% rhenium did not evidence unexpected results for the entire claimed range of about 1-3% rhenium); In re Grasselli, 713 F.2d 731, 741, 218 USPQ 769, 777 (Fed. Cir. 1983) (Claims were directed to certain catalysts containing an alkali metal. Evidence presented to rebut an obviousness rejection compared catalysts containing sodium with the prior art. The court held this evidence insufficient to rebut the prima facie case because experiments limited to sodium were not commensurate in scope with the claims.).
In this instant case, the prior art demonstrates the use of an anti-sST2 antibody in fulminant myocarditis and exemplifies experimental FM mice showed better survival rates when treated with an anti- sST2 antibody as noted above.
Closest Prior Art
The closest prior art made of record for claim 20 is Hang et al (Fulminant myocarditis: a comprehensive review from etiology to treatments and outcomes. Signal Transduct Target Ther. 2020 Dec 11;5(1):287). Hang et al teaches an overview of fulminant myocarditis, treatment methods, and teaches known biomarkers that are elevated in this disease. However, Hang et al does not teach levels of CD163 expression and use of an anti-CD163 antibody.
Conclusion
Conclusion: No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH A ALSOMAIRY whose telephone number is (571)272-0027. The examiner can normally be reached Monday-Friday 7:30 AM to 5:30 PM.
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, Gregory Emch can be reached at (571) 272-8149. 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.
/SARAH A ALSOMAIRY/Examiner, Art Unit 1646
/Zachariah Lucas/Supervisory Patent Examiner, Art Unit 1600
Prosecution Insights