DETAILED ACTION 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. Priority Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed on 12/01/2023. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Th is application is a 371 application, filed 12/01/2023, of PCT application PCT/EP2022/064616, which claims priority benefits from Foreign Application No. EP21305727.6, filed 06/01/2021. The effective filing date of this application is 06/01/2021 , the filing date of the Foreign Application No. EP21305727.6. Claims Status The application filed 12/01/2023 is entered. Claims 1-4 are pending and under examination. Information Disclosure Statement The information disclosure statement (IDS) submitted on 12/01/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. Nucleotide and/or Amino Acid Sequence Disclosures REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES Items 1) and 2) provide general guidance related to requirements for sequence disclosures. 37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted: In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying: the name of the ASCII text file; ii) the date of creation; and iii) the size of the ASCII text file in bytes; In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying: the name of the ASCII text file; the date of creation; and the size of the ASCII text file in bytes; In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended). When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824. If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical. If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical. Specific deficiencies and the required response to this Office Action are as follows: Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above. Required response – Applicant must provide: A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of: A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version); A copy of the amended specification without markings (clean version); and A statement that the substitute specification contains no new matter. Claim Rejections - 35 USC § 103 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 (i.e., changing from AIA to pre-AIA) 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. 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. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. 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. Claim s 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over WO ‘651 (WO2006076651A2; published 07/20/ 2006 ; IDS filed 12/01/2023, foreign patent reference #1 ) , in view of US ‘272 (US20170246 2 72A1, published 08/31/ 2017) , as evidenced by Guilherme et al ( Guilherme, L., et al, Rheumatic Fever and Rheumatic Heart Disease: Cellular Mechanisms Leading Autoimmune Reactivity and Disease, J Clin Immunol (2010) 30:17-23; published 10/03/2009 ) . Regarding claim 1, WO ‘651 teaches a method of treating (where “treating” and “treatment” and “alleviation” are defined as synonymous; page 11, line 31) an autoimmune disease in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a B-cell depleting agent (page 5, lines 19-35). WO ‘651 does not explicitly teach treating rheumatic heart disease. However, WO ‘651 further teaches examples of autoimmune diseases include rheumatic fever (page 9, line 32). As evidenced by the definitions of Guilherme et al, a specific bacterial infection can lead to development of rheumatic fever , and a complication of rheumatic fever leads to rheumatic heart disease , which is characterized by progressive and permanent heart valve lesions ( page 17, Introduction section of Abstract ) . WO ‘651 further teaches that rituximab, which is a CD20-specific B cell depleting agents, has been studied in autoimmune diseases in which B cells and autoantibodies play a role in the disease pathophysiology, and in many cases have shown therapeutic potential (page 1, line 40 – page 2). Furthermore, US ‘272 teaches that rheumatic heart disease is an “antibody-mediated autoimmune disorder” or a “B cell mediated autoimmune disease”, which is a disease where tissue injury is caused by an autoantibody response to autoantigens (page s 3-4, paragraphs 24-28 and Table 1). Specifically for rheumatic heart disease, the antibody response to the causative infectious bacteria cross -r eacts to human cardiac muscle ( page 4, Table 1) . Specifically cross-reactivity occurs through a phenomenon known as molecular mimicry between the bacteria antigen and human protein, as evidenced by Guilherme et al (page 17, Conclusion section in Abstract) . Although US ‘272 teaches B cell depletion therapies in addition to T cell vaccines for treating autoimmune disease, the underlying reason for B cell depletion is to reduce autoreactivity from B cells and autoantibodies (paragraph 49-52). It would have been obvious to one skilled in the art, before the effective filing date of the instant application, to use a B-cell depleting approach to treating rheumatic heart disease for the following reasoning . In light of the teachings by WO ‘651 regarding B cell depletion as a promising treatment approach for autoimmune diseases due to their pathophysiology, it would have been obvious to one skilled in the art, before the effective filing date of the instant application, to adapt B cell depletion for other autoimmune diseases not already trialed , such as rheumatic fever, which WO ‘651 specifically identifies. Considering the common causative agent between rheumatic fever and rheumatic heart disease that Guilherme teaches , it would have been obvious to one skilled in the art, before the effective filing date of the instant application, to adapt B cell depletion specifically for rheumatic heart disease, especially in light of the teachings by US ‘272 specifically teaching autoantibodies implicated in rheumatic heart disease and the use of B cell depleting agents as one approach to counteract these autoantibodies. Regarding the teachings of US ‘272 teaching B cell depleting therapy in addition to T cell vaccines to treat autoimmune disease, o ne skilled in the art, before the effective filing date of the instant application, would understand that rheumatic heart disease is a multifactorial disease and recognize the two approaches tackle different (i.e. autoreactive B cell vs. autoreactive T cell) but related parts of the same disease pathophysiology (i.e. reducing autoreactivity) . In other words, the teachings of a multipronged approach , where each prong independently but also synergistically addresses autoreactivity, does not discount the potential therapeutic benefits of the B cell depletion approach independently, as B cell depletion does not inherently require T cell vaccination. Additionally , the instant specification defines “treat” to encompass both preventive, curative, and disease modifying strategies (page 2, lines 17-21). As rheumatic heart disease is a potential complication of rheumatic fever, it would have been obvious to one skilled in the art, before the effective filing date of the instant application, that treating rheumatic fever, as WO ‘651 teaches , would prevent rheumatic heart disease development, and therefore “treat” (as instantly defined) it. One skilled in the art, before the effective filing date of the instant application, would be motivated to use a B-cell depleting approach to treating rheumatic heart disease in light of the disease pathophysiology and the promising results in other B cell mediated autoimmune disease. Furthermore, although there is motivation to find treatments for all autoimmune diseases listed in WO ‘651 , rheumatic heart disease belongs to a type of autoimmune disease that permanently damages a specific organ, so even if a patient could be treated, the organ damage perseveres , as evidenced by Guilherme et al . Even further, rheumatic fever and rheumatic heart disease is notable in that it affects children , by nature of its progression from untreated strep throat infections, which is common in children, as evidenced by Guilherme et al . As such, there is especially high motivation in the field to adapt treatment approaches from other autoimmune disease towards rheumatic heart disease specifically . One skilled in the art, before the effective filing date of the instant application, would have reasonable expectation of success adopting B-cell depleting approach to treating rheumatic heart disease in light of the promising effects of this treatment approach in other diseases that share a common pathophysiology. Furthermore, rheumatic heart disease, by nature of being an organ-specific B cell mediated autoimmune disorder, is inherently a more contained autoimmune disorder than systemic B cell mediated autoimmune disorders, such as lupus, which is characterized by broad spectrum autoantibodies against ubiquitous cellular components (US ‘272, page 4, Table 1). One skilled in the art, before the effective filing date of the instant application, would have more reasonable expectation of success that B cell depletion could help alleviate a specific autoantibody against a specific organ in comparison to a disease comprising of broad spectrum autoantibodies targeting different organs and functions, each with their own downstream effects. Additionally , unlike autoimmune diseases that manifest spontaneously, rheumatic heart disease progresses from rheumatic fever and a known specific bacterial infection, and has distinct major measurable events leading up to it and during it that can be monitored for (Guilherme et al, Figure 3); therefore, in some ways, is rheumatic heart disease is one of the more preventable autoimmune diseases that could benefit from B cell depletion. WO ‘651 further teaches that the desired level of B cell depletion, controlled by dosage, will depend on the disease, severity, and condition of the individual patient (page 20, lines 31-33) so one skilled in the art, before the effective filing date of the instant application, would have reasonable expectation that this therapy can be modulated accordingly in new diseases uses . KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, (2007) discloses that known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art, before the effective filing date of the claimed invention, and that this variation is obvious. The scope and content of the prior art, whether in the same field of endeavor as that of the applicant’s invention or a different field of endeavor, included a similar or analogous method. In this case, the prior art discloses a method of treating autoimmune diseases with a B cell depleting agent because of their autoantibody/B-cell mediated pathophysiology. The prior art discloses that rheumatic heart disease is an autoantibody/B-cell mediated autoimmune diseases and that B cell depletion is indicated to address this pathophysiology. The prior art teaches rituximab in a method of treating autoimmune diseases mediated by autoantibodies. Therefore, the variation of treating rheumatic heart disease with B cell depleting agents, which is within the same field of endeavor of the prior art teachings, is predictable to one of ordinary skill in the art, before the effective filing date of the claimed invention. There were design incentives or market forces which would have prompted adaptation of the known method. In this case, the prior art, as evidenced by Guilherme et al, which explicitly defines rheumatic heart disease, provides motivation to adapt B cell depleting therapy specifically for rheumatic heart disease specifically. The differences between the claimed invention and the prior art were encompassed in known variations or in a principle known in the prior art. In this case, the differences between the invention and the prior art is the autoimmune disease explicitly being taught, although the prior art teaches a disease with common pathophysiology as the instantly claimed disease and teaches the instantly claimed disease as a potential disease of interest. One of ordinary skill in the art, before the effective filing date of the claimed invention, in view of the identified design incentives or other market forces, could have implemented the claimed variation of the prior art, and the claimed variation would have been predictable due to the logic of using a therapeutic agent that addresses the pathophysiology of the disease, i.e. the autoantibodies created by B cells. Claims 2-4 depend on claim 1 . The teachings of the references regarding claim 1 are incorporated in its entirety for the dependent claims and discussed further below, as is relevant for each claim. Regarding claim 2, WO ‘651 further teaches the B cell depleting agent is an antibody having specificity for CD20 (page 5, lines 19-25) , arriving at all the limitations of the claim . Regarding claim 3, WO ‘651 further teaches that the anti-CD20 antibody could be a human anti-CD20 antibody, such as ofatumumab (i.e. HuMax-CD20); a chimeric anti-CD20 antibody, such as rituximab (page 6, lines 13-18) ; or a humanized anti-CD20 antibody (page 6, lines 13-18), such as ocrelizumab (page 26, line 40) , arriving at all the limitations of the claim . Regarding claim 4, WO ‘651 further teaches more preferably, the CD20 antibody is rituximab, or a list of three other antibodies (page 16, lines 41-44) and claims in one embodiment the CD20 binding antibody the method of treating autoimmune disease by B cell depletion is rituximab (WO ‘651, claim 27), arriving at all the limitations of the claim . WO ‘651 further teaches specifically rituximab (also known as Rituxan, C2B8, IDEC-C2B8, Mabthera, and GP2013) have been studied in a variety of non-malignant autoimmune disorders, in which B cells and autoantibodies appear to play a role in disease pathophysiology (page 1, line 40 to page 4, line 19) . In their examples, WO ‘651 teaches anti-CD20 antibodies effects in comparison to rituximab as a positive effect control (e.g. Examples 2-3 and Figure 2), effectively teaching rituximab in the method. Prior Art Made Of Record and Not Relied Upon The prior art made of record and not relied upon is considered pertinent to applicant's disclosure : Robertz et al ( Robertz, J. et al, Obinutuzumab in two patients suffering from immune-mediated thrombotic thrombocytopenic purpura intolerant to rituximab , Am J Hematol, 94: E259-E261 ; published 07/18/ 2019) This reference is made of the record to support that the prior art, despite known adverse events from rituximab and situational treatment failures, does not categorically teach away rituximab, and certainly not anti-CD20 antibodies, in treating autoantibody-mediated diseases. Robertz et al teaches rituximab is generally well tolerated and beneficial in diseases comprising autoantibodies in its disease pathophysiology , such as immune-mediated thrombotic thrombocytopenic purpura ( iTTP ) (paragraph 1) . Although Robertz teaches a patient with concurrent iTTP and rheumatic heart disease, treated with rituximab, failed to normalize levels of ADAMTS13 , which is the target of autoantibodies in iTTP (paragraph 3) , Robertz also teaches rituximab may have infusion-related reactions and patients may be allergic or become intolerant to rituximab (paragraph 2) . Therefore, the rituximab treatment may have failed due to an individual reaction to rituximab, and not because it categorically would not work in addressing the autoantibodies pathophysiology. In fact, rituximab generally has lower rates of infusion-related adverse events compared to the other anti-CD20 antibody that was subsequently prescribed (paragraph 5) , further pointing to an individual reaction that is not representative of the general population. The prior art previously presented also teaches that low dose anti-CD20 antibodies can be used to deplete B cells ( WO ‘651, e.g. abstract) , and that an initial conditioning dose lower than the therapeutically effective dose may be prescribed to minimize these infusion-related symptoms (WO ‘ 651 , page 23, line 27-34 ) , touching at the potential breadth of dosing that could be leveraged to minimize any infusion-related adverse activity . As such, Robertz et al does not teach away the use of rituximab in autoantibody-mediated autoimmune diseases. It logically recommends an alternative anti-CD20 antibody for patients that are allergic or develop intolerance to rituximab. One skilled in the art, before the effective filing date, would understand that rituximab is still a reasonable treatment option to try. Conclusion No claims are allowed. 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