DETAILED ACTION
Status of Application, Amendments and/or Claims
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The amendment of 4/9/26 has been entered in full. Claims 17, 19-20, 23-24, 26-27, 29 and 31 are amended. Claims 25 and 33-35 are canceled. Claims 17, 19-24, 26-32 and 36 are pending.
Applicants' election without traverse of Group II, currently all pending claims, in was previously acknowledged. The elections without traverse of (1) tafamidis as the species of TTR tetramer stabilizer, and (2) ATTR cardiomyopathy as the species of disease, was also previously acknowledged. Claims 29-32 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 17, 19-24, 26-28 and 36 are under consideration, as they read upon the elected species.
Information Disclosure Statement
The Information Disclosure Statement of 4/9/26 has been considered.
Withdrawn Objections and/or Rejections
All rejections of canceled claims 25 and 33-35 are moot.
The objection to claim 20 at page 2 of the 1/28/26 Office action is withdrawn in view of the amendments to the claims.
The rejection of claims 17, 19-24, 26-28 and 36 at pages 3-7 of the 1/28/26 Office action under 35 U.S.C. 112(a) for failing to comply with the written description requirement is withdrawn in view of the amendments to the claims.
Maintained Objections and/or Rejections
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claims 17, 19-24, 27 and 36 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Grimm et al, U.S. Patent Application 2016/0355576, published 12/8/16 (cited on the 1/16/25 IDS). The earliest date to which the instant application claims priority is 5/12/20. This rejection was set forth at pages 7-9 of the 1/28/26 Office Action.
Independent claim 17 has been amended to limit the claimed method to administering therapeutically effective amounts of each of the anti-transthyretin (TTR) antibody and the stabilizer, and further to limit the stabilizer to one selected from a group including tafimidis (which is the elected species under consideration) and the antibody to one comprising a variable heavy chain (VH) comprising CDRs1-3 of positions 31-35, 52-67 and 100-109 of SEQ ID NO: 2 or SEQ ID NO: 6, and a variable light chain (VL) comprising CDRs1-3 of positions 24-34, 50-56, and 89-97 of SEQ ID NO: 4.
The claims as amended have been fully considered but are met by the teachings of ‘576. As set forth previously for claim 17, ‘576 teaches “a method comprising a subject in need of treating ATTR [transthyretin amyloidosis] an anti-TTR antibody and a TTR tetramer stabilizer” (page 8 of the 1/28/26 Office action), and treatment with compound(s) of interest necessarily entails administration of a therapeutically effective amount of such compound(s). Furthermore, as set forth previously for dependent claims 25 (now canceled) and 27 (now amended to be limited to tafamidis meglumine), “’576 further teaches that the agents that stabilize the TTR-tetramer include Tafimidis Meglumine (¶ 321)” (page 9). And with respect to the anti-TTR antibody, as set forth previously, the instant application teaches that SEQ ID NO: 2 and 4 “are the VH and VL sequences of the antibody NI-301.37F1 (¶ 266, published application)” (page 9). Also as set forth previously for dependent claims 23 and 24 (each now amended), “[t]he exemplary antibodies of the invention of ‘576 include this same NI-301.37FI antibody having the same VH and VL sequences; see Figure 1C of ‘576, which shows these same amino acid sequences” (page 9). As this antibody comprises the VH and VL amino acid sequences of SEQ ID NO: 2 and 4, it necessarily also contains the positions corresponding to the CDRs that are newly recited in claim 17. As such, the teachings of ‘576 meet the limitations of the claims as amended.
At pages 7-8 of the reply, Applicants argue that ‘576 (Grimm et al) does not anticipate claim 17 as amended “under the test articulated in Net MoneyIn, given that Grimm does not disclosed every aspect of claim 17 as structured in claim” (page 8). Applicants point to Grimm disclosing “20 anti-TTR antibodies (Grimm, FIGS. 1A-1T)” and that anti-TTR antibodies may differ from these by one to three amino acids in the CDR2 or CDR3 regions (page 8). Applicants further point to Grimm disclosing TTR tetramer stabilizers “in an expansive list of agents “useful for treating a disease or disorder related to misfolded, misassembled, mutated and/or aggregated TTR”, with the list reciting “many particular agents and numerous genera of agents” (page 8). Applicants argue that in view of this, “Grimm merely discloses anti-TTR antibody and a TTR tetramer stabilizer as individual elements in isolation rather than the specific combination recited in the present claims” (page 8).
This argument has been fully considered but is not found to persuasive. While it is acknowledged that ‘576 discloses 20 anti-TTR antibodies, the NI-301.37F1 antibody is disclosed throughout the publication as one of three exemplary anti-TTR antibodies, e.g., at ¶ 18, 177, 187 and 189. Furthermore, while it is acknowledged that ‘576 provides a list of other agents that can be co-administered with an anti-TTR antibody, these agents are stated to be ones “useful for treating a disease or disorder related to misfolded, misassembled, mutated and/or aggregated TTR” (¶ 321), and the first subgenus of agents that is listed is “[a]gents which stabilize the TTR-tetramer” (¶ 321) and the first specific example of such that is tafamidis meglumine. Thus, ‘576 in ¶ 321 specifically teaches co-administration of an anti-TTR antibody that is NI-301.37F1 with an agent for treating a disease related to related to misfolded, misassembled, mutated and/or aggregated TTR that is an agent that stabilizes TTR that is tafamidis meglumine. As such, it is not found persuasive that ‘576 does not teach the elements in “the specific claimed combination” as argued by Applicants. Furthermore, per MPEP 2123, “"The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)).”
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
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 at the time any inventions covered therein were effectively filed 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 at the time a later invention was effectively filed 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.
Claims 26 and 28 are rejected under 35 U.S.C. 103(a) as being unpatentable over Grimm et al, U.S. Patent Application 2016/0355576, published 12/8/16 (cited on the 1/16/25 IDS), as applied to claims 17, 19-25, 27 and 36 above, and further in view of the Label for VYNDAQEL/VYNDAMAX; issued 05/2019, distributed by Pfizer. 16 pages. Available at https://www.fda.gov/media/126283/download (cited previously). This rejection was set forth at pages 9-11 of the 1/28/26 Office Action.
At page 9, Applicants reiterate arguments advanced with respect to the rejection of parent claim 17 under 35 U.S.C. 102(a)(1) as being anticipated by the ’576 publication. Applicants further argue that ‘576 teaches 20 different anti-TTR antibodies and 44 different secondary agents, which allows for “880 possible combinations”, and “with no expectation that any particular combination would achieve successful treatment of ATTR by promoting or inducing clearance of ATTR fibrils through ADCP, as is required by the instant claims” (page 9). Applicant point to MPEP 2143 in support. Applicants further argue that “Label”, which is the secondary reference, “fails to cure the deficiencies of Grimm”, as it does not suggest use of tafamidis “in combination with another agent” (page 9).
This argument has been fully considered but are not found persuasive. As set forth above, Applicants’ arguments with respect to the rejection of independent parent claim 17 under 35 U.S.C. 102(a)(1) as anticipated by the ‘576 publication are not found persuasive, and it is maintained that the ‘576 publication alone teaches the method of claim 17 that combines administration of the specified anti-TTR antibody and tafamidis. As such, Applicants’ arguments directed against the obviousness of combining the two treatments are not persuasive as the rejection of claims 26 and 28 is directed solely to the obviousness of further modifying the administered daily dosage of the combination already taught by ‘576.
At pages 10-11, Applicants further argue that the rejection under 35 U.S.C. 103(a) should be withdrawn “in view of Applicant’s evidence showing the combination of the recited anti-TTR antibody and a TTR tetramer stabilizer is surprisingly effective for promoting or inducing ATTR fibril clearance by ADCP, which result was unexpected and was observed solely by the present Applicant” (page 10). In support, Applicants point to the results of the experiments described in Examples 2 and 3, as providing evidence that administration of the combination of tafamidis and the anti-TTR antibody enhance clearance of transthyretin fibrils over administration of the antibody alone in a mouse model of ATTR (pages 10-11). Applicants argue that this enhanced clearing could not have been predicted by the teachings of either reference cited in the rejection (pages 10-11).
Applicants argument have been fully considered but are not found persuasive. Per MPEP 716.02(e), allegations of unexpected results must be “must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness”. Only claims 26 and 28 are rejected under 35 U.S.C. 103(a). Therefore, with respect to the rejection of claims 26 and 28 under 35 U.S.C. 103(a) as unpatentable over the teachings of Grimm et al in view of the “Label for Label for VYNDAQEL/VYNDAMAX”, the closest prior art is the primary reference, Grimm et al, which teaches all of the limitations of the method of parent claim 17, as maintained above. The only difference between parent claim 17 and each of dependent claims 26 and 28 is the specific daily dosages of tafamidis administered to the subject. As such, in order to rebut the prima facie case of obviousness, the evidence of unexpected results must compare the specific claimed subject matter of dependent claims 26 and/or 28, i.e., the results of a method employing the specific daily dosages of tafamidis of dependent claims 26 and/or 28 as administered in combination with the anti-TTR antibody, to the results of the closest prior art, i.e., the results of a method administering tafamidis in conjunction with an anti-TTR antibody as taught by the ‘576 publication, which generally encompasses a broad range of any dosages of tafamidis. Applicants do not provide any evidence employing the specific daily dosages required by claims 26 or 28 that show evidence of unexpected results when these dosages are employed.
New rejections necessitated by Applicants’ amendment
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.-Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), fourth paragraph:
Subject to the [fifth paragraph of 35 U.S.C. 112 (pre-AIA )], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 23 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Per MPEP 608.01(n).III, “If the dependent claim does not comply with the requirements of 35 U.S.C. 112(d), the examiner should reject the dependent claim under 35 U.S.C. 112(d) rather than objecting to the claim” and “a dependent claim must be rejected under 35 U.S.C. 112(d) if it omits an element from the claim upon which it depends or it fails to add a limitation to the claim upon which it depends”.
Claim 23 depends from independent claim 17, and further limits the antibody employed by the method to one that is capable of binding a TTR epitope which comprises or consists of the amino acid sequence WEPFA (SEQ ID NO: 7). However, this epitope is bound by an antibody of parent claim 17, that comprises the CDRs of the VH and VL regions of SEQ ID NO: 2 or 4 (VH) and SEQ ID NO: 6 (VL). As such, the claim 23 fails to further limit parent claim 17 because it recites a property that is already possessed by the antibody employed by the method. Therefore, dependent claim 23 is of improper dependent form because it fails to further limit the subject matter of parent claim 17.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
No claims are allowed.
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 extension fee 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 ZACHARY C HOWARD whose telephone number is (571)272-2877. The examiner can normally be reached on Monday to Friday from 9 AM to 5 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford, can be reached at telephone number (571) 272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZACHARY C HOWARD/Primary Examiner, Art Unit 1674
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