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 .
Application Status
Claims 1-14 are pending and examined on the merits herein.
Grounds of Rejection Withdrawn
Previous objection to the specification is withdrawn in view of amendment.
Previous objection to claims 4-11 are withdrawn in view of claim amendments.
Previous rejection of claims 1 and 3 under 35 U.S.C. 112(b) are withdrawn in view of claim amendments.
Claim Objections
Claim 7 and 9 are objected to because of the following informalities:
Claim 7 recites “wherein the fragment is selected from fragments, scFv,” but should read “wherein the fragment is selected from fragments: scFv”;
Claim 9 recites two options for the hybrid molecule but there is no recitation of the conjunction “or” between these options in line 5;
Appropriate correction is required.
Claim Rejections - 35 USC § 102
New Rejection Necessitated by Amendment
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.
Claims 1-2, 4, 7, 10, 12, and 14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chu (EP 2176298 B1; IDS entered 09/18/2023).
Regarding claim 1, Chu teaches an immunoglobulin Fc fusion that is covalently linked to an autoantigen selected from citrullinated fibrinogen (para 0009), wherein the target antigen of the immunoglobulin include CD38 and/ or CD138 (para 0086).
Regarding claims 2, 4, and 14, Chu teaches that conjugate partners may be linked to any region of an immunoglobulin disclosed herein, including at the N- or C- termini, or at some residue in-between the termini and further that a variety of linkers may find use to covalently link conjugate partners to an immunoglobulin including PEG (para 0141). Use of a PEG linker inherently requires an integer of at least 1 unit of PEG.
Regarding claim 7, Chu teaches in one embodiment, the antibody is an antibody fragment including, but are not limited to the Fab fragment, the Fv fragment, single chain Fv molecules (scFv) or F(ab')2 fragments (para 0080).
Regarding claims 10 and 12, Chu teaches methods of treating B cell- mediated disorders such as autoimmune diseases, including rheumatoid arthritis (para 0006).
Response to Arguments
Applicant's arguments filed 08/07/2026 have been fully considered but they are not persuasive.
Applicant submits: Chu mentions that, in one embodiment, the autoantigen is selected from the group consisting citrullinated proteins and peptides such as CCP-1, CCP2 (cyclical citrullinated peptides), fibrinogen, fibrin,…
First of all, it should be noted that Chu does not disclose citrullinated fibrin, but rather mentions fibrin, as an alternative to citrullinated proteins among other proteins or other molecules such as nucleic acids. It should also be noted that even if Chu mentions CD38 and CD138 among a list of target antigens, Chu never specifically discloses a fusion between a citrullinated fibrin-derived peptide and an antibody capable of binding to CD38 and/or CD138. Consequently, Chu cannot anticipate claim 1. For the same reason Chu cannot anticipate claim 2 even if it discloses linkers such as PEG in paragraph [0141] of Chu). Claims 1-2 are therefore novel in view of Chu.
In Response: Chu does disclose citrullinated fibrin. As detailed in the rejection above and also noted in the remarks from applicant above, Chu teaches an embodiment wherein the autoantigen is selected from the group consisting of citrullinated proteins and peptide such as…fibrin, therefore the entire list of proteins and peptides that follow as options including fibrin are citrullinated. This is not an alternative to a citrullinated protein or peptide as shown by the verbiage “such as”.
The listed embodiments in Chu include an immunoglobulin Fc fusion molecule comprising an immunoglobulin targeting CD38 or CD138 and a citrullinated fibrin; while not specifically listed together the teaching of the embodiments together is still anticipatory.
Claim Rejections - 35 USC § 103
New Rejection Necessitated by Amendment
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.
Claims 3, 5-6, 8, 11, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Chu (EP 2176298 B1; IDS entered 09/18/2023) as applied to claims 1-2, 4, 7, 10, 12, and 14 above and further in view of Lelieveldt (Sl: sn, 2019; cited in OA 05/07/2026), Clavel (US 9,388,226 B2; PTO-892) and Schoenfield (US 9,975,944 B2; PTO-892).
The teachings of Chu regarding claims 1-2, 4, 7, 10, 12, and 14 are detailed above.
Chu does not teach wherein said peptide is derived from all or part of the sequence of the alpha or beta chain of a vertebrae fibrin by substitution of at least one arginyl residue by a citrullyl residue; the sequence of the citrullinated fibrin; a hybrid molecule comprising multiple plasma cell targets; treatment with multiple hybrid molecules.
Regarding claims 3 and 13, Lelieveldt teaches affinity matrix (AM) technology comprising anti-CD138 F(ab)2 fragments conjugated to an autoantigen (Fig 10; Page 29). Lelieveldt further teaches that all plasma cells will be coated with the AM, however, the matrix will only capture any antigen-selective antibodies if those are secreted by the cell, wherein the cells will subsequently undergo complement mediated lysis (page 29). Lelieveldt further teaches that rheumatoid arthritis (RA) is hallmarked by the presence of anti-citrullinated protein antibodies (ACPA) that sustain destructive inflammation (page 30, paras 4-5) and that citrullinated fibrinogen is an autoantigen in RA that has been targeted with β60-74Cit peptide which is the major epitope of citrullinated fibrinogen (page 31, last para; Fig 11-12).
Regarding claims 8 and 11, Lelieveldt teaches that CD44 or CD138 can be used in the AM technology conjugated to autoantigens to target plasma cells and further was used in mice to target autoreactive long lived plasma cells in mice (page 29).
Regarding claim 5, Clavel teaches the sequence of β60-74cit is SEQ ID NO: 19 which has 100% sequence identity to the instant claimed SEQ ID NO: 1.
Regarding claims 6 and 11, Clavel teaches the idenitifcation of several fibrin-derived citrullinated peptides bearing epitopes specifically recognized by anti-citrullinated protein autoantibodies (ACPAs) (example 2) including α411-425cit which has SEQ ID NO: 13 and β210-224cit which has SEQ ID NO20 (table 1); which have 100% sequence identity to the instant claimed SEQ ID NO: 13 and 20 respectively.
Regarding claim 11, Schoenfield teaches there remains an unmet need for therapeutic approaches for the treatment of autoimmune diseases, such as, rheumatoid arthritis which do not involve broad immune suppression.(background). Schoenfield further teaches a method of treating an autoimmune disease comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a synthetic peptide and a pharmaceutically acceptable carrier, wherein said peptide comprises the amino acid sequence set forth in SEQ ID NO: 1, wherein the autoimmune disease is rheumatoid arthritis (claim 1), wherein said subject is an ACPA+ RA patient (claim 6). Schoenfield further teaches the use of citrullinated peptides from fibrin as tolerogenic agents for restoration of immune-tolerance while avoiding general immune suppression, wherein the synthetic peptide comprises a plurality of epitopes, each epitope being derived from a protein selected from the group consisting of: fibrinogen-a, beta-firbrinogen… (summary of invention).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to treat ACPA mediated disease using the β60-74Cit peptide as taught by Lelieveldt as the autoantigen in the anti-CD138 (or CD38)-spacer-autoantigen fusion as taught by Chu. The ordinary artisan would have been motivated to do so because Lelieveldt teaches that citrullinated fibrinogen is an autoantigen in RA that has been targeted with β60-74Cit peptide which is the major epitope of citrullinated fibrinogen and Chu is also targeting citrullinated fibrinogen. Lelieveldt further teaches that using this AM platform plasma cells will be coated with the AM, however, the matrix will only capture any antigen-selective antibodies if those are secreted by the cell, wherein the cells will subsequently undergo complement mediated lysis. Clavel teaches the idenitifcation of several fibrin-derived citrullinated peptides bearing epitopes specifically recognized by anti-citrullinated protein autoantibodies (ACPAs). The ordinary artisan has a reasonable expectation of success to use the β60-74Cit peptide to generate an anti-CD138 (or CD38)-spacer- β60-74Cit peptide (autoantigen) fusion and to use this hybrid molecule for treatment of an autoimmune disease mediated by ACPA.
It would further be obvious to use multiple citrullinated peptides recognized by ACPAs as taught by Schoenfield using the sequences that were validated to be targeted by ACPA by Clavel to generate multiple fusion molecules as taught by Chu to target ACPA producing plasma cells as taught by Lelieveldt. The ordinary artisan would have been motivated to do so as Schoenfield teaches there remains an unmet need for therapeutic approaches for the treatment of rheumatoid arthritis which do not involve broad immune suppression and the use of multiple citrullinated peptides derived from fibrin as a therapeutic approach. Lelieveldt teaches targeting of ACPA plasma cells using AM technology using an antibody to target plasma cells fused to an autoantigen, which would be even more effective with multiple constructs. Clavel teaches several fibrin-derived citrullinated peptides bearing epitopes specifically recognized by anti-citrullinated protein autoantibodies. The ordinary artisan has a reasonable expectation of success to treat rheumatoid arthritis using multiple fusion molecules between plasma targeting antibodies and citrullinated fibrin peptides to deplete plasma cells and serve an unmet clinical need in rheumatoid arthritis patients.
Applicant submits: This Figure shows that in Chu the immunoglobulins bind to FcyRllb by its Fc region and to another antigen (here depicted as CR) on the surface of the same cell expressing FcyRllb by its variable region.
To the contrary, the aim of the present invention is to target plasma cells secreting anti- citrullinated protein autoantibodies (ACPA) in abundance in their microenvironment and to eliminate them using a hybrid molecule comprising (i) a fibrin-derived peptide having at least one citrullyl residue and (ii) an antibody or antibody fragment which binds to CD38 and/or CD138. These hybrid molecules will target plasma cells (using the antibody or antibody fragment which binds to CD38 and/or CD138, which are molecular markers expressed on the surface of said plasma cells) and, thanks to the fibrin-derived peptide having at least one citrullyl residue, the hybrid molecule will be recognised specifically by the ACPA (the peptide being the target of these ACPA). After bridging (binding of ACPA to the hybrid molecule, itself bound to plasma cells), the plasma cells will be lysed by apoptosis, by phagocytosis in the presence of macrophages, by ADCC (antibody- dependent cell-mediated cytotoxicity) in the presence of NK cells, or by complement activation. By targeting the plasma cells that secrete ACPA, the hybrid molecules of the invention thus aim to cause the disappearance of the ACPA from the patients' bodies and of the source of these ACPA to induce a remission of the disease.
Chu does not teach, nor suggest, the lysis of the plasma cells. Consequently, the skilled person cannot be motivated to do so in view of Chu. Chu does not teach, nor suggest, to use the Fc fragment of the ACPA to bind to FcyRs expressed on the surface of a macrophage or a NK cell in order to eliminate plasma cells. Consequently, the skilled person cannot be motivated to do so in view of Chu.
In Response: While the intended mechanism of action of the fusion molecules is different between Chu and the instant application, claim 3 is not drawn to the mechanism of action or even a method of using the invention but to the composition itself.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., lysis of plasma cells) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Further, Lelieveldt does teach lysis of plasma cells using the AM technology of a CD138 Fab conjugated to an autoantigen as detailed in the 103 rejection above. Therefore, the mechanism of the 103 rejection and the instant application are the same.
Double Patenting
New Rejection Necessitated by Amendment
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of copending Application No. 18/551,129 (reference application) in view of Lelieveldt (Sl: sn, 2019; cited in OA 05/07/2026) and Schoenfield (US 9,975,944 B2; PTO-892).
Regarding claim 1, the copending claims teach a hybrid molecule comprising at least one antibody Fc fragment covalently linked to at least one fibrin-derived peptide having at least one citrullyl residue, at least one spacer being optionally present between said Fc fragment and said peptide (claim 1).
Regarding claims 2 and 4, the copending claims teach wherein said spacer is a polymer containing one or more repeating units containing the ether group, said spacer preferably being polyethylene glycol of formula PEGn, wherein n represents an integer between 1 and 100 (claim 3).
Regarding claims 3 and 13, the copending claims teach wherein said peptide is derived from all or part of the sequence of the a or B chain of a vertebrate fibrin by substitution of at least one arginyl residue by a citrullyl residue, said vertebrate fibrin being human fibrin (claim 2).
Regarding claim 5, the copending claims teach wherein said peptide comprises at least one citrullyl residue, and is selected from the group consisting of: a) a peptide defined by the sequence X1PAPPPISGGGYX2AX3 (SEQ ID NO: 1) wherein X1, X2, and X3 each represent a citrullyl residue or an arginyl residue, and at least one of the X1 or X2 or X3 residues is a citrullyl residue; b) a peptide defined by the sequence GPX1VVEX2HQSACKDS (SEQ ID NO: 2) wherein X1 and X2 each represent a citrullyl residue or an arginyl residue, and at least one of the Xi or X2 residues is a citrullyl residue; c) a peptide defined by the sequence SGIGTLDGFX1HX2HPD (SEQ ID NO: 3) wherein X1 and X2 each represents a citrullyl residue or an arginyl residue, and at least one of the X1 or X2 residues is a citrullyl residue; d) a peptide defined by the sequence VDIDIKIX1SCX2GSCS (SEQ ID NO: 4) wherein X1 and X2 each represent a citrullyl residue or an arginyl residue, and at least one of the Xi or X2 residues is a citrullyl residue; e) a peptide defined by the sequence X1GHAKSX2PVX3GIHTS (SEQ ID NO: 12) wherein X1, X2 and X3 each represent a citrullyl residue or an arginyl residue, and at least one of the X1 or X2 or X3 residues is a citrullyl residue; f) a peptide comprising at least 5 consecutive amino acids, including at least one citrullyl residue, from one of the peptides a) to e) above (claim 4), SEQ ID NO: 1-4 and 12 have 100% sequence identity to the instant claimed same SEQ ID NO.
Regarding claim 6, the copending claims teach wherein said peptide is selected from the group consisting of: SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22 and SEQ ID NO: 23 (claim 5), SEQ ID NO: 13 has 100% sequence identity to the same instant claimed SEQ ID NO.
Regarding claims 9 and 14, the copending claims teach a wild-type Fc fragment that is bound to at least one PEGn spacer that is itself coupled to an azide covalently bound to a cyclooctyne that is coupled to a peptide represented by SEQ ID NO: 19 or SEQ ID NO: 18, - an Fc fragment comprising the S239D, H268F, S324T and 1332E mutations that is bound to at least one PEGn spacer that is itself coupled to an azide covalently bound to a cyclooctyne that is coupled to a peptide represented by SEQ ID NO: 19 or SEQ ID NO: 18, - an Fc fragment comprising the L234A, L235A and P329G mutations that is bound to at least one PEGn spacer that is itself coupled to an azide covalently bound to a cyclooctyne that is coupled to a peptide represented by SEQ ID NO: 19 or SEQ ID NO: 18, - a wild-type Fc fragment that is bound to a PEGn spacer that is itself coupled to at least one azide covalently bound to a cyclooctyne coupled to a PEGn spacer that is itself bound to a peptide represented by SEQ ID NO: 19 or SEQ ID NO: 18, - an Fc fragment comprising the S239D, H268F, S324T and 1332E mutations that is bound to at least one PEGn spacer that is itself coupled to an azide covalently bound to a cyclooctyne coupled to a PEGn spacer that is itself bound to a peptide represented by SEQ ID NO: 19 or SEQ ID NO: 18, n preferably representing an integer between 1 and 10 (claim 9).
Regarding claim 10, the copending claims teach method for the treatment of autoimmune diseases associated with the production of anti-citrullinated protein autoantibodies, in particular Gougerot-Sjogren syndrome and rheumatoid arthritis comprising the administration of a hybrid molecule according to claim 1 (claim 10).
Regarding claim 12, the copending claims teach wherein said autoimmune disease is Gougerot-Sjogren syndrome or rheumatoid arthritis (claim 12).
The copending claims do not teach that the antibody fragment targets CD38 or CD138.
Regarding claims 1 and 7 Lelieveldt teaches affinity matrix (AM) technology comprising anti-CD138 F(ab)2 fragments conjugated to an autoantigen used to deplete autoreactive memory plasma cells (Fig 10. Page 29). Lelieveldt further teaches that all plasma cells will be coated with the AM, however, the matrix will only capture any antigen-selective antibodies if those are secreted by the cell, wherein the cells will subsequently undergo complement mediated lysis (page 29). Lelieveldt further teaches that rheumatoid arthritis (RA) is hallmarked by the presence of anti-citrullinated protein antibodies (ACPA) that sustain destructive inflammation (page 30, paras 4-5) and that citrullinated fibrinogen is an autoantigen in RA that has been targeted with β60-74Cit peptide which is the major epitope of citrullinated fibrinogen (page 31, last para; Fig 11-12).
Regarding claims 8 and 11, Lelieveldt teaches that CD44 or CD138 can be used in the AM technology conjugated to autoantigens to target plasma cells and further was used in mice to target autoreactive long lived plasma cells in mice (page 29).
Regarding claim 11, Schoenfield teaches there remains an unmet need for therapeutic approaches for the treatment of autoimmune diseases, such as, rheumatoid arthritis which do not involve broad immune suppression.(background). Schoenfield further teaches a method of treating an autoimmune disease comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a synthetic peptide and a pharmaceutically acceptable carrier, wherein said peptide comprises the amino acid sequence set forth in SEQ ID NO: 1, wherein the autoimmune disease is rheumatoid arthritis (claim 1), wherein said subject is an ACPA+ RA patient (claim 6). Schoenfield further teaches the use of citrullinated peptides from fibrin as tolerogenic agents for restoration of immune-tolerance while avoiding general immune suppression, wherein the synthetic peptide comprises a plurality of epitopes, each epitope being derived from a protein selected from the group consisting of: fibrinogen-a, beta-firbrinogen… (summary of invention).
It would further be obvious to use multiple citrullinated peptides recognized by ACPAs as taught by Schoenfield using the sequences that were validated to be targeted by ACPA by Clavel to generate multiple fusion molecules as taught by Chu to target ACPA producing plasma cells as taught by Lelieveldt. The ordinary artisan would have been motivated to do so as Schoenfield teaches there remains an unmet need for therapeutic approaches for the treatment of rheumatoid arthritis which do not involve broad immune suppression and the use of multiple citrullinated peptides derived from fibrin as a therapeutic approach. Lelieveldt teaches targeting of ACPA plasma cells using AM technology using an antibody to target plasma cells fused to an autoantigen, which would be even more effective with multiple constructs. Clavel teaches several fibrin-derived citrullinated peptides bearing epitopes specifically recognized by anti-citrullinated protein autoantibodies. The ordinary artisan has a reasonable expectation of success to treat rheumatoid arthritis using multiple fusion molecules between plasma targeting antibodies and citrullinated fibrin peptides to deplete plasma cells and serve an unmet clinical need in rheumatoid arthritis patients.
It would have been obvious to one of ordinary skill in the art to target CD138 as taught by Lelieveldt in the Fc fragment antibody-citrullinated fibrin hybrid molecule as taught by the copending claims. The ordinary artisan would have been motivated to do so because Lelieveldt teaches that anti-CD138 fragments conjugated to an autoantigen can be used to deplete autoreactive memory plasma cells while sparing non-reactive B cells. The ordinary artisan has a reasonable expectation of success to use an anti-CD138 Fc fragment to generate an anti-CD138 -spacer-citrullinated fibrin peptide fusion
Further, it would have been obvious to one of ordinary skill in the art to treat ACPA mediated disease using the fusion autoantigen peptide- CD138 (Fab)2 as taught by Lelieveldt using the multiple peptides as taught Schoenfield with the sequences as taught by the copending claims. The ordinary artisan would have been motivated to do so because all three of these arts are directed to treatment of rheumatoid arthritis using citrullinated fibrinogen peptides. Schoenfield teaches there remains an unmet need for therapeutic approaches for the treatment of rheumatoid arthritis which do not involve broad immune suppression and the use of multiple citrullinated peptides derived from fibrin as a therapeutic approach. The copending claims teach treatment of rheumatoid arthritis with a hybrid molecule comprising at least one citrullinated fibrin peptide. Lelieveldt teaches that anti-CD138 fragments conjugated to an autoantigen can be used to deplete autoreactive memory plasma cells while sparing non-reactive B cells. The ordinary artisan has a reasonable expectation of success to treat rheumatoid arthritis using multiple fusion molecules between plasma targeting antibodies and citrullinated fibrin peptides to deplete plasma cells and serve an unmet clinical need in rheumatoid arthritis patients.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 08/07/2026 have been fully considered but they are not persuasive.
Applicant submits: As mentioned above the aim of the present invention is to target plasma cells secreting anti-citrullinated protein autoantibodies (ACPA) in abundance in their microenvironment and to eliminate them using a hybrid molecule comprising (i) a fibrin-derived peptide having at least one citrullyl residue and (ii) an antibody or antibody fragment which binds to CD38 and/or CD138.
The aim of the invention of the Reference Application is different: it is to target B lymphocyte clones expressing ACPAs on their surface and to eliminate them using a hybrid molecule comprising (i) at least one fibrin-derived peptide having at least one citrullyl residue and (ii) an Fc fragment of human immunoglobulin. These hybrid molecules will specifically target ACPA- positive B lymphocytes (using the fibrin-derived peptide having at least one citrullyl residue, which is recognized by said ACPAs), which will then be eliminated, after the Fc fragment binds to the Fc receptors of cells by macrophages (via phagocytosis) and/or NK cells (via antibody-dependent cell- mediated will then be eliminated, after the Fc fragment binds to the Fc receptors of cells by macrophages (via phagocytosis) and/or NK cells (via antibody-dependent cell-mediated.
The claimed invention and the invention as described in the Reference Application are therefore two distinct inventions, each one aiming to eliminate different target cells. The Fc fragment of the Reference Application is essential to eliminate the B cells, therefore the skilled person cannot be motivated to remove this part of the hybrid molecule. Consequently, the two inventions are distinct and patentable. There is no double patenting and withdrawal of the rejection is requested.
In response: The overall aim of the application does not negate that it is obvious in view of the prior art, in particular prior art that teaches the same goal: lysis of ACPA producing plasma cells using antibodies that target plasma cells conjugated to autoantigens for autoimmune disease (Lelieveldt supra).
The Fc portion of the reference application can be replaced by an anti CD138 antibody as taught by the prior art to generate the same result: depletion of B cells.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMBER K FAUST whose telephone number is (703)756-1661. The examiner can normally be reached Monday - Thursday 9:00am-6:00pm EST.
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/AMBER K FAUST/Examiner, Art Unit 1643
/GARY B NICKOL/Primary Examiner, Art Unit 1643
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