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
This application was filed 8/10/2023 and is a 371 of PCT/US2022/015917 (02/10/2022) which has a provisional 63/149124 (01/12/2021). Claims 1-4, 6, 14, 18, 21-22, 28-31, 34, 39, 43, 45-46, 50 and 52 are before the Examiner.
Response to Amendment
The rejection of claims 31, 34, 39, 43, 45-46, 50 and 52 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as stated in paper dated 12/09/2025, is withdrawn in view of applicants amendments to the claims in paper dated 04/09/2026.
The rejection of claims 31, 34, 39, 43, 45, 46, 50 and 52 under 35 USC 112(b) or 35 USC 112 (pre-AIA ), second paragraph, as stated in paper dated 12/09/2025, is withdrawn in view of applicant’s amendments and arguments in paper dated 04/09/2026.
The rejection of claims 1-2 under 35 U.S.C. 102(a)(1) as being anticipated by US Pat 9994537 Cisar, as stated in paper dated 12/09/2025, is withdrawn in view of applicant’s amendments and arguments in paper dated 04/09/2026.
The rejection of claims 1-4, 6, 14, 18, 21-22, 28-31, 34, 39, 43, 45, 46, 50 and 52 under 35 U.S.C. 102(a)(1) as being anticipated by Cioffi, as stated in paper dated 12/09/2025, is withdrawn in view of applicant’s amendments and arguments in paper dated 04/09/2026.
The rejection of claims 31, 34, 39, 43, 45-46, 50 and 52 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for stabilizing TTR tetramers, does not reasonably provide enablement for treating TTR amyloidosis disease, treating a disease characterized by excessive lipofuscin or treating a disease characterized by a TTR amyloidosis disease or by excessive lipofuscin accumulation in the retina or both a TTR amyloidosis disease and a disease characterized by excessive lipofuscin, as stated in paper dated 12/09/2025, is upheld.
As previously stated, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”. These factors include 1) the breadth of the claims, 2) the nature of the invention, 3) the state of the prior art, 4) the level of one of ordinary skill, 5) the level of predictability in the art, 6) the amount of direction provided by the inventor, 7) the existence of working examples, and 8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The nature of the invention: The nature of the invention is the method of treating a disorder that is modulated by TTR.
The state of the prior art: The state of the prior art is that it involves screening in vitro and in vivo to determine which compounds exhibit the desired pharmacological activities (i.e. what compounds can treat which specific disease). There is no absolute predictability even in view of the seemingly high level of skill in the art. The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any therapeutic regimen on its face.
The predictability in the art: It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F. 2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. In the instant case, the instantly claimed invention is highly unpredictable since one skilled in the art would recognize that in regards to the therapeutic effects of all diseases, whether or not the modulation of TTR would make a difference in the disease. Hence, in the absence of a showing of a nexus between any and all known diseases and the modulation TTR, one of ordinary skill in the art is unable to fully predict possible results from the administration of the compound of claim 1 due to the unpredictability of the role of modulation of TTR. Those of skill in the art recognize that in vitro assays and or cell-cultured based assays are generally useful to observe basic physiological and cellular phenomenon such as screening the effects of potential drugs. Garai and Li both teach that TTR activity is important and might be useful to treat diseases in the future.
The presence or absence of working examples: The compounds of the instant invention have been shown to work in vitro and in vivo for the TTR activity. However, there are no working examples of the instant compounds treating a specific disease.
The amount of direction or guidance present: The guidance present in the specification is that of the compounds have TTR activity. But applicant teaches that this activity might have use to treat diseases. This is stated in the last paragraph in the instant specification. The instant compounds are a novel class of TTR tetramer kinetic stabilizers that show promise. The specification does not seem to enable a correlation between the mediation of TTR and the treatment of all the diseases linked to TTR activity.
The breadth of the claims: The claims are drawn to the treatment of many diseases mediated by TTR with the compound of claim 1.
The quantity of experimentation needed: The quantity of experimentation needed is undue. One skilled in the art would need to determine what disease out of all diseases known to be linked to TTR would be benefited by the mediation of TTR and then would further need to determine which of the claimed compounds would provide treatment of the disease.
The level of the skill in the art: The level of skill in the art is high. However, due to the unpredictability in the pharmaceutical art, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro and in vivo screening to determine which compounds exhibit the desired pharmacological activity and which diseases would benefit from this activity.
Thus, the specification fails to provide sufficient support of the broad use of the compounds of claim 1 for the treatment of “disease”. As a result necessitating one of ordinary skill to perform an exhaustive search for which diseases can be treated by which compound of claim 1 in order to practice the claimed invention.
Genentech Inc. v. Novo Nordisk A/S (CA FC) 42 USPQ2d 1001, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, one of ordinary skill in the art would have to engage in undue experimentation to test which diseases can be treated by the compounds of the instant claims, with no assurance of success.
This rejection can be overcome by limiting the claims to the stabilizing TTR tetramers in a mammal (the first listed treatment in claim 31).
Applicant’s Arguments:
Applicants argue that the nexus between treating TTR amyloidosis disease is taught on page 2 lines 21-26. However, this teaches that “…free dimer subunits may subsequently further dissociate into monomers that could potentially proceed to misfold and oligomerize.” May and could potentially proceed. Both of these are vague and not currently expected to happen. Might and potentially. Not a current known utility but a possible future possibility. This does not show enablement for treating a TTR amyloidosis disease (method (c) and (e) for claim 31). Further, applicant does not state what diseases are encompassed by this broad treatment of TTR amyloidosis disease. There are also no examples of the instant compounds treating any TTR amyloidosis disease.
Applicants argue (for claim 31 method (d) and (e)) that the discussion on page 5-6 of the specification teach that the claimed RBP4 antagonist compounds as possible therapeutic agents for treating diseases characterized by excessive lipofuscin accumulation. However, the discussion referred to only discusses potential of RBP4 antagonists to reduce accumulation of lipofuscin in the retina and not treating any disease characterized by excessive lipofuscin (part (e) of claim 31). Further, applicant does not have any working examples of the instant compounds treating a disease characterized by excessive lipofuscin accumulation in the retina or any disease characterized by excessive lipofuscin.
Applicants have no argument for the reduction of TTR aggregate formation or inhibiting formation of high molecular weight aggregates in a mammal (part (b) of claim 31).
Due to this, the rejection of claims 31, 34, 39, 43, 45-46, 50 and 52 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for stabilizing TTR tetramers, does not reasonably provide enablement for treating TTR amyloidosis disease, treating a disease characterized by excessive lipofuscin or treating a disease characterized by a TTR amyloidosis disease or by excessive lipofuscin accumulation in the retina or both a TTR amyloidosis disease and a disease characterized by excessive lipofuscin, as stated in paper dated 12/09/2025, is upheld.
Allowable Subject Matter
Claims 1-4, 6, 14, 18, 21, 22 and 28-30 are allowed.
Conclusion
Claims 31, 34, 39, 43, 45-46, 50 and 52 are rejected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to D MARGARET M SEAMAN whose telephone number is (571)272-0694. The examiner can normally be reached M-F 8am-4pm Eastern.
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/D MARGARET M SEAMAN/Primary Examiner, Art Unit 1625
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