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
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
2. Applicant’s amendment filed January 02, 2026 is acknowledged. Claims 1-24, 36-40 and 42-43 are canceled. Claims 25-28 are amended. Claims 45-46 are newly added. Claims 25-35, 41, 44 and new claims 45-46 are pending in this application. Election was made without traverse in the reply filed on August 29, 2025.
3. Claims 25-35, 41 and 44-46 are under examination with respect to SEQ ID NOs: 37 and 57 for VH and VL; SEQ ID NOs: 42, 47, 52 and SEQ ID NOs: 62, 67 and 72 for HCDRs1-3 and LCDRs-13; and SEQ ID NOs: 131-132 for HC and LC in this office action.
4. Applicant’s arguments filed on January 02, 2026 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
Specification
5. The disclosure stands objected to because no generic terminology is accompanied with the term “Biacore™” (p. 52-55; p. 57-58 of the amended specification filed 01/02/2026),”Mesoscale®” (p. 56 of the amended specification filed 01/02/2026), “Alexa Fluor” (p. 60 of the amended specification filed 01/02/2026). Appropriate correction is required.
Claim Rejections/Objections Withdrawn
6. The objection to claims 36-40 and 42-43 is moot because the claims ae canceled.
The rejection of claims 25-35, 41 and 44 on the basis that it contains an improper Markush grouping of alternatives is withdrawn in response to Applicant’s amendment to the claims.
The rejection of claims 27-28 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in response to Applicant’s amendment to the claims.
The rejection of claims 27-28 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement is withdrawn in response to Applicant’s amendment to the claims.
Claim Rejections/Objections Maintained
In view of the amendment filed on January 02, 2026, the following rejections are maintained.
Claim Rejections - 35 USC § 112
7. Claims 25, 27-35, 41 and 44 stand 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. The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 25, 27-35, 41 and 44 as amended encompass a genus of anti-MuSK antibody comprising a VH and a VL, wherein the VH comprises structurally and functionally undefined HCDRs1-3 sequences of the VH of SEQ ID NO:37 and the VL comprises structurally and functionally undefined LCDRs1-3 sequences of the VL of SEQ ID NO:57.
Claims 27-28 as amended encompass a genus of anti-MuSK antibody variants comprising a VH and a VL, wherein the VH that comprises an amino acid sequence at least 90% identical to SEQ ID NO:37 and the VL comprises an amino acid sequence at least 90% identical to SEQ ID NO:57 or a genus of anti-MuSK antibody variants comprising a HC that comprises an amino acid sequence at least 90% identical to SEQ ID NO:131 and a LC that comprises an amino acid sequence at least 90% identical to SEQ ID NO:132.
Claim 30 as amended encompass a genus of human heavy chain constant region that does not have a complement effector functionality.
Claim 32 as amended encompass a genus of human heavy chain constant region that comprises one or more structurally and functionally undefined mutations.
Claim 35 encompasses a genus of anti-MuSK agonist antibody comprising structurally and functionally undefined HCDRs1-3 sequences of the VH of SEQ ID NO:37 and the VL comprises structurally and functionally undefined LCDRs1-3 sequences of the VL of SEQ ID NO:57.
Applicant has not disclosed sufficient species for the broad genus of anti-MuSK antibody comprising structurally and functionally undefined HCDRs1-3 sequences of the VH of SEQ ID NO:37 and structurally and functionally undefined LCDRs1-3 sequences of the VL of SEQ ID NO:57, the broad genus of anti-MuSK agonist antibody thereof, the broad genus of anti-MuSK antibody variants and the broad genus of anti-MuSk antibody having a genus of human heavy chain constant region that does not have a complement effector functionality or a genus of one or more structurally and functionally undefined mutations.
Response to Arguments
On p. 9 of the response, Applicant argues that Applicant is in possession of the claimed anti-MusK antibody recited in independent claim 25 because a skilled artisan would know HCDRs1-3 of SEQ ID NO:37 and LCDRs1-3 of SEQ ID NO:57. Applicant further cites Kabat et al. (J. Biol. Chem., 1977; 252:6609-6616), Kabat et al. (1991), Chothia et al. (J. Mol. Biol., 1987; 196:901-917 and MacCallum et al. (J. Mol. Biol., 1996; 262:732-745) in support of the arguments.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2163, MPEP §§2163.01-2163.03, the specification fails to provide sufficient description or information or evidence to demonstrate that Applicant is in possession of the claimed genus of anti-MuSK antibody, anti-MuSK agonist antibody comprising undefined sequences for HCDRs1-3 and LCDRs1-3 or anti-MuSK antibody variants because of the following:
i. The structural and functional relationship or correlation between the claimed genus of anti-MuSK antibody comprising structurally and functionally undefined CDRs of VH and VL of recited SEQ ID NOs: and the defined sequences for HCDRs1-3 and LCDRs1-3 of anti-MuSK antibodies 3F6c, 3D11a, 4D3, 3D9b and 3B5 is unknown.
Based on p. 9 of the specification filed 01/02/2026, the HCDRs1-3 and LCDRs1-3 of the claimed antibody encompass “variant CDR sequences….” and “at least 50%.....”. Based on p. 12 of the specification filed 01/02/2026, the HCDRs1-3 and LCDRs1-3 of the claimed antibody encompass the positions for LCDRs are amino acids (aa) 24-34 (LCDR1), aa 50-56 (LCDR2) and aa 89-97 (LCDR3) in the VL, and the positions for HCDRs1-3 in the VH are aa 24-34 (HCDR1), aa 50-65 (HCDR2) and aa 95-102 (HCDR3) of the VH based on Kaba…(p. 12-13, table 1).
The specification only describes anti-MuSK antibodies 3F6c, 3D11a, 4D3, 3D9b and 3B5 and their corresponding sequences for HC/LC, VH/LC and HCDRs1-3/LCDRs1-3 on p. 49-50, tables 3-4 and their activity of agonizing MuSK and inducing MuSK phosphorylation in mouse C2C12 myotubes (p. 60, Example 11, table 24) and AChR clustering (p. 60-, Examples 12-13, Tables 25-28).
SEQ ID NOs:
Ab HC VH HCDRs1-3 LC VL LCDRs1-3
3F6c 131 37 42/47/52 132 57 62/67/72
3D11a 127 36 41/46/51 128 56 61/66/71
4D3 129 38 43/48/53 130 58 63/68/73
3D9b 133 35 40/45/50 134 55 60/65/70
3B5 125 39 44/49/54 126 59 64/69/74
Applicant is in possession of anti-MuSK antibodies 3F6c, 3D11a, 4D3, 3D9b and 3B5 and their corresponding sequences for HC/LC, VH/LC and HCDRs1-3/LCDRs1-3 on p. 49-50, tables 3-4. However, Applicant is not in possession of other structurally and functionally undefined anti-MuSK antibody variants having structurally and functionally undefined HCDRs1-3 and LCDRs1-3 or the genus of anti-MuSK antibody variants structurally and functionally undefined VH and VL having at least 90% identity to SEQ ID NOs: 37 and 57 or structurally and functionally undefined HC and LC having at least 90% identity to SEQ ID NOs: 131-132 or comprising structurally and functionally undefined human heavy chain constant region that does not have a complement effector functionality or that comprises one or more undefined mutations.
The specification fails to teach what specific sequences for HCDRs1-3 and LCDRs1-3 of the claimed anti-MuSK antibodies or anti-MuSK agonist antibodies are and their structural and functional relationship to the anti-MuSK antibody 3F6c or other anti-MuSK antibodies recited in Tables 3-4.
Neither the specification nor the prior art teaches what other structurally and functionally undefined variant antibodies are and can possess the claimed biological binding properties as claimed.
ii. The structural and functional relationship or correlation between the claimed genus of anti-MuSK antibody variants comprising at least 90% identity to recited SEQ ID NOs:37 for VH and VL and the defined sequences for VH and VL of anti-MuSK antibody 3F6c or other anti-MuSK antibodies recited in Tables 3-4 is unknown.
The structural and functional relationship or correlation between the claimed genus of anti-MuSK antibody variants comprising at least 90% identity to SEQ ID NOs: 131 and 132 for heavy chain (HC) and light chain (LC) and the defined sequences for HC and LC of anti-MuSK antibody 3F6c or other anti-MuSK antibodies recited in Tables 3-4 is unknown.
The specification fails to teach what other structures/amino acid sequences are required for the claimed genus of variant antibodies comprising an amino acid sequence at least 90% identical to the VH of SEQ ID NO:37 and an amino acid sequence at least 90% identical to the VL of SEQ ID NO:57; and what 10% sequences within the recited SEQ ID NOs: 37 and 57 for VH and VL can or cannot be changed in order to preserve the activity and binding ability of an anti-MuSK antibody having the VH of SEQ ID NO:37 and the VL of SEQ ID NO:57.
The specification fails to teach what other structures/amino acid sequences are required for the claimed genus of variant antibodies comprising an amino acid sequence at least 90% identical to the HC of SEQ ID NO:131 and an amino acid sequence at least 90% identical to the LC of SEQ ID NO:132; and what 10% sequences within the recited SEQ ID NOs: 131-132 for the HC and LC can or cannot be changed in order to preserve the activity and binding ability of an anti-MuSK antibody having the HC of SEQ ID NO:131 and the LC of SEQ ID NO:132.
Neither the specification nor the prior art teaches what other structurally and functionally undefined variant antibodies are and can possess the biological binding properties as instantly claimed.
iii. The structural and functional relationship or correlation between the claimed genus of human heavy chain constant region with no complement effector functionality or one or more undefined mutations and the human IgG heavy chain constant region comprising L234A and L235A mutations according to the EU numbering system.
The specification fails to teach what other structures/amino acid sequences are required for the claimed genus of human heavy chain constant region comprising structurally and functionally undefined sequences and with no complement effector functionality or one or more undefined mutations.
Neither the specification nor the prior art teaches what other structurally and functionally undefined variant antibodies comprising a human heavy chain constant region with no complement effector functionality or one or more undefined mutations are and still can possess the biological binding properties as instantly claimed.
Since the common characteristics/features of other structurally and functionally undefined anti-MuSK antibody variants or the genus of anti-MuSK antibody variants structurally and functionally undefined VH and VL having at least 90% identity to SEQ ID NOs: 37 and 57 or structurally and functionally undefined HC and LC having at least 90% identity to SEQ ID NOs: 131-132 or comprising structurally and functionally undefined human heavy chain constant region that does not have a complement effector functionality or that comprises one or more undefined mutations are unknown, a skilled artisan cannot envision the functional correlations of the genus with the claimed invention in view of Rudikoff et al. (see p. 1979; Proc. Natl. Acad. Sci. USA 1982 Vol. 79: page 1979, cited previously), Burgess et al. (J of Cell Bio. 1990, 111:2129-2138, cited previously), Bowie et al. (see col 2, p. 1306, Bowie et al. Science, 1990, 247:1306-1310, cited previously), Pawson et al. (see p. 445 the second column, first paragraph, Pawson et al. 2003, Science 300:445-452, cited previously), Alaoui-lsmaili et al. (see p. 502, right col., 2th paragraph; Alaoui-lsmaili et al., Cytokine Growth Factor Rev. 2009; 20:501-507, cited previously), and Guo et al. (see p. 9207, left col., 2th paragraph, Guo et al., PNAS 2004; 101:9205-9210, cited previously).
Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus of anti-MuSK antibody variants comprising structurally and functionally undefined CDRs of VH and VL of recited SEQ ID NOs:, the claimed genus of anti-MuSK antibody variants comprising at least 90% identity to recited SEQ ID NOs:37 for VH and VL, the claimed genus of anti-MuSK antibody variants comprising at least 90% identity to SEQ ID NOs: 131 and 132 for HC and LC and the claimed genus of anti-MuSK antibody variants comprising the genus of human heavy chain constant region with no complement effector functionality or one or more undefined mutations.
Based on MPEP § 2161.01 and §2163, “to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116”.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “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).
As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of anti-MuSK antibody variants comprising structurally and functionally undefined CDRs of VH and VL of recited SEQ ID NOs:, the claimed genus of anti-MuSK antibody variants comprising at least 90% identity to recited SEQ ID NOs:37 for VH and VL, the claimed genus of anti-MuSK antibody variants comprising at least 90% identity to SEQ ID NOs: 131 and 132 for HC and LC and the claimed genus of anti-MuSK antibody variants comprising the genus of human heavy chain constant region with no complement effector functionality or one or more undefined mutations, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483 and Centocor v. Abbott, 636 F.3d1341 (Fed. Cir. 2011) and AbbVie v. Janssen, 759 F.3d 1285 (Fed. Cir.2014). One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483.
Therefore, the claimed anti-MuSK antibody variants have not met the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement. See MPEP § 2161.01 and 2163.
Accordingly, the rejection of claims 25, 27-35, 41 and 44 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 is maintained.
Claim Rejections - 35 USC § 102
8. 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 25, 27-32, 34-35, 41 and 44 stand rejected under 35 U.S.C. 102(a)(2) as being anticipated by Van der Maarel et al. (WO2020055241). The rejection is maintained for the reasons of record, and the reasons set forth below.
Claims 25, 27-32, 34-35, 41 and 44 as amended are drawn to an anti-MuSK antibody comprising a VH and a VL, wherein the VH comprises HCDRs1-3 sequences of the VH of SEQ ID NO:37 and the VL comprises LCDRs1-3 sequences of the VL of SEQ ID NO:57.
Response to Arguments
On p. 9-10 of the response, Applicant argues that i) Van der Maarel et al. (WO2020055241) does not teach an LCDR3 with a serine at position 96 as required by claim 25; ii) the claimed SEQ ID NO:57 has a serine at position 96 of LCDR3 using Kabat, Chothia and MacCallum system based on p. 12-13, Table 1 of the instant specification whereas the corresponding sequence taught by Van der Maarel et al. (WO2020055241) has a cysteine at this position.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2131, Van der Maarel et al. (WO2020055241) does teach the claimed invention because of the following:
i. 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. a serine at position 96 of LCDR3 in SEQ ID NO:57) 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).
ii. Claims 25, 27-32, 34-35, 41 and 44 as amended are drawn to an anti-MuSK antibody comprising a VH and a VL, wherein the VH comprises HCDRs1-3 sequences of the VH of SEQ ID NO:37 and the VL comprises LCDRs1-3 sequences of the VL of SEQ ID NO:57.
The HCDRs1-3 sequences of the VH of SEQ ID NO:37 and the VL comprises LCDRs1-3 sequences of the VL of SEQ ID NO:57 recited in claim 25 are not limited to specific sequences or comprise or consist of the sequences of SEQ ID NOs: 42,47, 52, 62, 67 and 72 for HCDRs1-3 and LCDRs1-3 respectively as recited in claim 26.
Based on p. 9 of the specification filed 01/02/2026, the HCDRs1-3 and LCDRs1-3 of the claimed antibody encompass “variant CDR sequences….” and “at least 50%.....”. Based on p. 12 of the specification filed 01/02/2026, the HCDRs1-3 and LCDRs1-3 of the claimed antibody encompass the positions for LCDRs are amino acids (aa) 24-34 (LCDR1), aa 50-56 (LCDR2) and aa 89-97 (LCDR3) in the VL, and the positions for HCDRs1-3 in the VH are aa 24-34 (HCDR1), aa 50-65 (HCDR2) and aa 95-102 (HCDR3) of the VH based on Kaba…(p. 12-13, table 1).
The anti-MuSK antibody disclosed by Van der Maarel meets the limitations recited in claims 25, 27-32, 34-35, 41 and 44 because:
i) The sequences of HCDRs1-3 and LCDRs1-3 recited in claim 25 are not specified, and are not limited to specific sequences of SEQ ID NOs: 42,47, 52, 62, 67 and 72 recited in claim 26 for HCDRs1-3 and LCDRs1-3 respectively, and also encompass variant sequences of HCDRs1-3 and LCDRs1-3 with at least 50%...to 100% identical to given sequences of HCDRs1-3 and LCDRs1-3 (see p. 9 and p. 12-13).
ii) The anti-MuSK antibody disclosed by Van der Maarel comprises a VH having the amino acid sequence of SEQ ID NO:17, which is 96.4% identical to instant SEQ ID NO:37 and a VL having the amino acid sequence of SEQ ID NO:21, which is 92.4% identical to instant SEQ ID NO:57 (see the sequence alignment below; p. 22; p. 30-34; p. 89-90; p. 103-104, table 5A-C, Example numbers 8-14), which meet the limitations “comprises a VH comprising the HCDRs1-3 sequences of the VH of SEQ ID NO:37 and a VL comprising the LCDR1-3 sequences of the VL of SEQ ID NO:57” recited in claim 25, “wherein the VH and VL comprise at least 90% identical to instant SEQ ID NOs:37 and 57 respectively” recited in claim 27 or “wherein the HC and LC comprise at least 90% identical to instant SEQ ID NOs: 131-132” recited in claim 28.
iii) The anti-MuSK antibody disclosed by Van der Maarel also comprises a human heavy chain constant region including the human heavy chain constant region that does not have a complement effector functionality or is human IgG1-4 constant region, one or more mutations recited in claims 29-32 and 34 (see p.5; p. 10; p. 67-68; p. 116-119, claims 10-14 and 32-36), wherein the anti-MuSK antibody is an agonistic antibody that agonizes MuSK and/or induces or increases induction of AChR clustering at the NMJ as in claim 35 (see p.5; p. 17-18; p.58; p. 82; p. 97-98).
iv) Van der Maarel also teaches a pharmaceutical composition comprising the claimed antibody and a pharmaceutically acceptable carrier or excipient or a kit comprising the claimed antibody as in claim 41 and 44 (see p 74-81).
Thus, claims 25, 27-32, 34-35, 41 and 44 are anticipated by Van der Maarel et al. (WO2020055241).
Accordingly, the rejection of claims 25, 27-32, 34-35, 41 and 44 under 35 U.S.C. 102(a)(2) as being anticipated by Van der Maarel et al. (WO2020055241) is maintained.
Claim Rejections - 35 USC § 103
9. 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 33 stands rejected under 35 U.S.C. 103 as being unpatentable over Van der Maarel et al. (WO2020055241) in view of Fallah-Arani et al. (US2017/0088603). The rejection is maintained for the reasons of record, and the reasons set forth below.
Response to Arguments
On p. 10 of the response, Applicant argues that for the reasons set forth above, Van der Maarel does not teach or suggest an LCDR3 with a serine at position 96 as required by claim 25.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2141, MPEP2141-I, rationales identified by the Court in KSR (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, 82 USPQ2d 1385 (2007)), MPEP2141-II, the basic factual inquires of Graham v. John Deere Co.(Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966)),and MPEP §2141.01-2147.03, the cited references do render the claimed invention obvious because:
i. For the reasons set forth above, Van der Maarel does teach the claimed invention recited in claims 25, 27-32, 34-35, 41 and 44.
ii. While Van der Maarel does not explicitly teach that the mutations in the human heavy chain constant region are L234A and L235A mutations numbered according to the EU numbering system as in claim 33, Fallah-Arani et al. (US2017/0088603) teach these limitations and provide motivation and an expectation of success because Fallah-Arani teaches the benefits of using a human heavy chain constant region/human IgG constant region comprising mutations including L234A and L235A mutations numbered according to the EU numbering system because a human heavy chain constant region/human IgG constant region comprising mutations including L234A and L235A mutations numbered according to the EU numbering system.provides improved therapies for use in the treatment of immune diseases involving pathogenic antibodies (see [0188]-[0193] and [0198]-[0199]; [0215]-[0216]; [0353]; [0407]-[0411]).
A person of ordinary skill in the art would have recognized that selecting and applying the known human heavy chain constant region/human IgG constant region comprising the known mutations L234A and L235A numbered according to the EU numbering system in the human heavy chain constant regions and the known technique disclosed by Fallah-Arani to the anti-MuSK antibody of Van der Maarel would have yielded the predictable result of better anti-MuSK antibody for use in the treatment diseases involving antibodies, and resulted in an improved product.
Using and including the known human heavy chain constant region/human IgG constant region comprising the known mutations L234A and L235A numbered according to the EU numbering system in the human heavy chain constant regions and the known technique disclosed by Fallah-Arani in the anti-MuSK antibody of Van der Maarel would provide a better anti-MuSK antibody for therapeutic purposes, and would expand application of the the anti-MuSK antibody of Van der Maarel and increase patient’s satisfaction with treatment using anti-MuSK antibodies.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known human heavy chain constant region/human IgG constant region comprising the known mutations L234A and L235A numbered according to the EU numbering system in the human heavy chain constant regions and the known technique disclosed by Fallah-Arani to the anti-MuSK antibody of Van der Maarel, and yield the predictable result of a better anti-MuSK antibody for therapeutic purposes.
Accordingly, the rejection of claim 33 under 35 U.S.C. 103 as being unpatentable over Van der Maarel et al. (WO2020055241) in view of Fallah-Arani et al. (US2017/0088603) is maintained.
Double Patenting
10. 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 25, 27-32, 34-35, 41 and 44 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, 10, 12, 14, 22-23, 25-26, 30, 32, 34, 36-38, 41 and 45-46 of copending Application No. 17/272792. The rejection is maintained for the reasons of record, and the reasons set forth below.
Response to Arguments
On p. 10 of the response, Applicant argues that Application No. 17/272792 is the corresponding US national phase application of Van der Maarel (WO2020055241) and for the reasons set forth above, clams 1, 5, 8, 10, 12, 14, 22-23, 25-26, 30, 32, 34, 36-38, 41 and 45-46 do not teach or suggest an LCDR3 with a serine at position 96 as required by claim 25.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP§804 and MPEP §2131, claims 1, 8, 10, 12, 14, 22-23, 25-26, 30, 32, 34, 36-38, 41 and 45-46 of Application No. 17/272792 (the ‘792 Application) do teach the claimed invention because of the following:
i. For the reasons set forth above under the 102 rejection, the anti-MuSK antibody recited in the claims of the ‘792 Application do anticipate instant claims.
In particular, the anti-MuSK antibody recited in the claims of the ‘792 Application comprises a VH having the amino acid sequence of SEQ ID NO:17, which is 96.4% identical to instant SEQ ID NO:37 and a VL having the amino acid sequence of SEQ ID NO:21, which is 92.4% identical to instant SEQ ID NO:57 (see the sequence alignment below), which meets the limitations recited in instant claims 27-28, and also comprises the claimed HCDRs1-3 and LCDRs1-3 recited in instant claims 25-26 because the HCDRs1-3 sequences of the VH of SEQ ID NO:37 and the VL comprises LCDRs1-3 sequences of the VL of SEQ ID NO:57 recited in claim 25 are not limited to specific sequences and based on p. 9 of the specification filed 01/02/2026, the HCDRs1-3 and LCDRs1-3 of the claimed antibody encompass “variant CDR sequences….”.
Therefore, claims 25, 27-32, 34-35, 41 and 44 of the instant Application are not patentably distinct from claims 1, 8, 10, 12, 14, 22-23, 25-26, 30, 32, 34, 36-38, 41 and 45-46 of the ‘792 Application because claims 25, 27-32, 34-35, 41 and 44 of the instant Application are anticipated by claims 1, 8, 10, 12, 14, 22-23, 25-26, 30, 32, 34, 36-38, 41 and 45-46 of the ‘792 Application.
Accordingly, the provisional rejection of claims 25, 27-32, 34-35, 41 and 44 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, 10, 12, 14, 22-23, 25-26, 30, 32, 34, 36-38, 41 and 45-46 of the ‘792 Application is maintained.
Conclusion
Allowable Subject Matter
11. Claims 26 and 45-46 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
12. Claims 25, 27-35, 41 and 44 are rejected.
13. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
The sequence search results disclose as follows:
Van der Maarel et al. (WO2020055241) (under the 102 rejection) teaches an anti-MuSK antibody 11-3F6 comprising a VH having the sequence of SEQ ID NO:17, which is 96.4% identical to instant SEQ ID NO:37 and a VL having the sequence of SEQ ID NO:21, which is 92.4% identical to instant SEQ ID NO:57 (see the sequence alignment below).
SEQ ID NO:37
BHM07874
(NOTE: this sequence has 1 duplicate in the database searched)
ID BHM07874 standard; protein; 121 AA.
XX
AC BHM07874;
XX
DT 03-JUL-2025 (revised)
DT 30-APR-2020 (first entry)
XX
DE Anti-MUSK monoclonal antibody (mAb) VH 11-3F6, SEQ ID 17.
XX
KW MUSK protein; Muscle specific kinase receptor; antibody therapy;
KW autoimmune disease; enzyme kinetics; heavy chain variale region;
KW immunosuppressive; injury; monoclonal antibody; motor neurone disease;
KW muscle disease; muscle-specific kinase protein; muscular dystrophy;
KW myasthenia gravis; neuromuscular disease; neuroprotective; sarcopenia;
KW therapeutic.
XX
OS Homo sapiens.
XX
FH Key Location/Qualifiers
FT Region 26..33
FT /label= CDR1
FT Region 51..58
FT /label= CDR2
FT Region 97..110
FT /label= CDR3
XX
CC PN WO2020055241-A1.
XX
CC PD 19-MAR-2020.
XX
CC PF 05-SEP-2019; 2019WO-NL050577.
XX
PR 10-SEP-2018; 2018NL-02021591.
PR 13-MAY-2019; 2019NL-02023120.
XX
CC PA (ZIEK ) ACAD ZIEKENHUIS LEIDEN HODN LUMC.
XX
CC PI Van Der Maarel SM, Verschuuren JJG, Huijbers MGM, Plomp JJ;
XX
DR WPI; 2020-22297W/030.
Query Match 96.4%; Score 612; Length 121;
Best Local Similarity 95.9%;
Matches 116; Conservative 3; Mismatches 2; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYTMDWVRQAPGKGLEWVSSIGSNGDYIYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYTMDWVRQAPGKGLEWVSSIGSNGDYIYY 60
Qy 61 ADSVRGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARGQLAVAGTHFDYWGQGTLVTVS 120
||||||||||||||||||||||||||| :||| |||||||||||||||||||:|:|||||
Db 61 ADSVRGRFTISRDNAKNSLYLQMNSLRPDDTADYYCARGQLAVAGTHFDYWGRGSLVTVS 120
Qy 121 S 121
|
Db 121 S 121
SEQ ID NO:57
BHM07878
(NOTE: this sequence has 1 duplicate in the database searched)
ID BHM07878 standard; protein; 107 AA.
XX
AC BHM07878;
XX
DT 03-JUL-2025 (revised)
DT 30-APR-2020 (first entry)
XX
DE Anti-MUSK monoclonal antibody (mAb) VL 11-3F6, SEQ ID 21.
XX
KW MUSK protein; Muscle specific kinase receptor; antibody therapy;
KW autoimmune disease; enzyme kinetics; immunosuppressive; injury;
KW light chain variale region; monoclonal antibody; motor neurone disease;
KW muscle disease; muscle-specific kinase protein; muscular dystrophy;
KW myasthenia gravis; neuromuscular disease; neuroprotective; sarcopenia;
KW therapeutic.
XX
OS Homo sapiens.
XX
FH Key Location/Qualifiers
FT Region 27..32
FT /label= CDR1
FT Region 50..52
FT /label= CDR2
FT Region 89..97
FT /label= CDR3
XX
CC PN WO2020055241-A1.
XX
CC PD 19-MAR-2020.
XX
CC PF 05-SEP-2019; 2019WO-NL050577.
XX
PR 10-SEP-2018; 2018NL-02021591.
PR 13-MAY-2019; 2019NL-02023120.
XX
CC PA (ZIEK ) ACAD ZIEKENHUIS LEIDEN HODN LUMC.
XX
CC PI Van Der Maarel SM, Verschuuren JJG, Huijbers MGM, Plomp JJ;
XX
DR WPI; 2020-22297W/030.
Query Match 92.4%; Score 508; Length 107;
Best Local Similarity 91.6%;
Matches 98; Conservative 4; Mismatches 5; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASQKVNKYVNWYQQKPGKAPKLLIYAASTLQSGVPS 60
|||||||||||||||||||||:|||||||||||||||| |||||:|||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTISCRASQKVNKYVNWYQQTPGKAPRLLIYAASTLQSGVPS 60
Qy 61 RFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSPLSTFGQGTKLEIK 107
|||||||| :|||||| ||||||| |:|||||||| |||||||||||
Db 61 RFSGSGSGANFTLTISGLQPEDFAIYFCQQSYSPLCTFGQGTKLEIK 107
US/17272792 (US20240043562) (under the double patenting rejection) teaches an anti-MuSK antibody having a VH comprising the amino acid sequence of SEQ ID NO:17, which is 96.4% identical to the claimed VH of instant SEQ ID NO:37 and a VL comprising the amino acid sequence of SEQ ID NO:21, which is 92.4% identical to instant SEQ ID NO:57 (see the sequence alignment below).
SEQ ID NO:37
Sequence 17, US/17272792A
Publication No. US20240043562A1
GENERAL INFORMATION
APPLICANT: Academisch Ziekenhuis Leiden (h.o.d.n. LUMC)
TITLE OF INVENTION: MuSK activation
FILE REFERENCE: 713180: AGX5-058US
CURRENT APPLICATION NUMBER: US/17/272,792A
CURRENT FILING DATE: 2021-10-07
PRIOR APPLICATION NUMBER: PCT/NL2019/050577
PRIOR FILING DATE: 2019-09-05
PRIOR APPLICATION NUMBER: NL2021591
PRIOR FILING DATE: 2018-09-10
PRIOR APPLICATION NUMBER: NL2023120
PRIOR FILING DATE: 2019-05-13
NUMBER OF SEQ ID NOS: 78
SEQ ID NO 17
LENGTH: 121
TYPE: PRT
ORGANISM: Homo sapiens
Query Match 96.4%; Score 612; Length 121;
Best Local Similarity 95.9%;
Matches 116; Conservative 3; Mismatches 2; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYTMDWVRQAPGKGLEWVSSIGSNGDYIYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYTMDWVRQAPGKGLEWVSSIGSNGDYIYY 60
Qy 61 ADSVRGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARGQLAVAGTHFDYWGQGTLVTVS 120
||||||||||||||||||||||||||| :||| |||||||||||||||||||:|:|||||
Db 61 ADSVRGRFTISRDNAKNSLYLQMNSLRPDDTADYYCARGQLAVAGTHFDYWGRGSLVTVS 120
Qy 121 S 121
|
Db 121 S 121
SEQ ID NO:57
Sequence 21, US/17272792A
Publication No. US20240043562A1
GENERAL INFORMATION
APPLICANT: Academisch Ziekenhuis Leiden (h.o.d.n. LUMC)
TITLE OF INVENTION: MuSK activation
FILE REFERENCE: 713180: AGX5-058US
CURRENT APPLICATION NUMBER: US/17/272,792A
CURRENT FILING DATE: 2021-10-07
PRIOR APPLICATION NUMBER: PCT/NL2019/050577
PRIOR FILING DATE: 2019-09-05
PRIOR APPLICATION NUMBER: NL2021591
PRIOR FILING DATE: 2018-09-10
PRIOR APPLICATION NUMBER: NL2023120
PRIOR FILING DATE: 2019-05-13
NUMBER OF SEQ ID NOS: 78
SEQ ID NO 21
LENGTH: 107
TYPE: PRT
ORGANISM: Homo sapiens
Query Match 92.4%; Score 508; Length 107;
Best Local Similarity 91.6%;
Matches 98; Conservative 4; Mismatches 5; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASQKVNKYVNWYQQKPGKAPKLLIYAASTLQSGVPS 60
|||||||||||||||||||||:|||||||||||||||| |||||:|||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTISCRASQKVNKYVNWYQQTPGKAPRLLIYAASTLQSGVPS 60
Qy 61 RFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSPLSTFGQGTKLEIK 107
|||||||| :|||||| ||||||| |:|||||||| |||||||||||
Db 61 RFSGSGSGANFTLTISGLQPEDFAIYFCQQSYSPLCTFGQGTKLEIK 107
14. THIS ACTION IS MADE FINAL. 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.
15. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached Monday-Thursday, 7:00am-5:00pm EST.
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, Jeffrey Stucker can be reached at 571-272-0911. 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.
Chang-Yu Wang
April 27, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
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