DETAILED ACTION
This office action is in response to the Applicant’s filing dated January 5th, 2024.
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 is a CON of 16/362,573 filed on March 22nd, 2019 now U.S. Patent No. 11,666,661; and has a PRO of 62/647,569 filed on March 23rd, 2018.
Status of Claims
Claims 133-152 are pending in the instant application. Acknowledgement is made of Applicant’s remarks and amendments filed on January 5th, 2024. Acknowledgment is made of Applicant’s cancelation of claims 1-132; and addition of new claims 133-152.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 135-142 and 145-152 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 reducing BDR4 levels in U2OS cells with BMF-1-64 on page 8, paragraph [0028] and Figure 13; and polyQ-HTT levels in U2OS cells with BMF-1-141 on page 8, paragraph [0031] and Figure 16, does not reasonably provide enablement for reducing the level of any cellular component in any cellular context. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. This is a scope of enablement rejection.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
3- the presence or absence of working examples,
4- the nature of the invention,
5- the state of the prior art,
6- the relative skill of those in the art,
7- the predictability of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
1. The nature of the invention and breadth of the claims
The invention relates to a method of reducing the level of a cellular component by contacting the cellular component with either BMF-1-64 or BMF-1-141.
Claims 135-142 and 145-152 are directed to a method of reducing the level of a cellular component by contacting the cellular component with either BMF-1-64 or BMF-1-141. Thus, the claims are extremely broad with regards to the cellular components targeted for degradation and the specific cellular contexts in which they are targeted.
2. The state and predictability of the art, and relative skill of those in the art
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using Applicant’s invention would generally be a physician with a M.D. degree and several years of experience.
The factor is outweighed, however, by the unpredictable nature of the art. It is well established that “the scope of enablement varies with the degree of unpredictability of the factors involved” and physiological activity is considered to be an unpredictable factor. See In re Fisher, 166 USPQ 18, at 24 (In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved); Nationwide Chemical Corporation, et. al. v. Wright, et. al., 192 USPQ 95 (one skilled in chemical and biological arts cannot always reasonably predict how different chemical compounds and elements might behave under varying circumstances); Ex parte Sudilovsky 21 USPQ2d 1702 (Applicant’s invention concerns pharmaceutical activity. Because there is no evidence of record of analogous activity for similar compounds, the art is relatively unpredictable); In re Wright 27 USPQ2d 1510 (the physiological activity of RNA viruses was sufficiently unpredictable that success in developing specific avian vaccine was uncertain).
As illustrative of the state of the art, the examiner cites Rubinsztein et al., cited for evidentiary purposes, teaches that the ultimate consequences for autophagy may not be straightforward. Excitotoxicity will increase calcium levels, which in turn inhibits autophagosome biogenesis; whereas mutant huntingtin binds the autophagy inducer Rhes to impair autophagy. Thus, the eventual consequences of a specific mutation or disease situation are frequently unpredictable, as multiple activating and inhibitory pathways may be affected. Furthermore, non–cell-autonomous effects may have an impact. For example, the increased nitric oxide released by glial cells in diseases such as Alzheimer’s disease impairs autophagosome biogenesis (page 980, right column, second paragraph). Menzies et al., cited for evidentiary purposes, teaches that while autophagy has been protective in some models, it may be toxic in others due to impaired autophagosome clearance, leading to unproductive accumulation and toxic consequences. Menzies further discloses that therapeutic outcomes depend critically on disease stage, timing of intervention and cellular context, and that effective autophagy-based therapies require more selective molecular tools and higher resolution understanding of autophagic flux (page 1025, right column, second paragraph).
“The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability of the art” In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970).
Accordingly, the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statutory requirements.
3. The amount of direction or guidance provided and the presence or absence of working examples
The specification provides western blot data for reducing BDR4 levels in U2OS cells with BMF-1-64 on page 8, paragraph [0028] and Figure 13; and polyQ-HTT levels in U2OS cells with BMF-1-141 on page 8, paragraph [0031] and Figure 16, but it is not sufficient to provide support for the full scope of reducing the level of any cellular component in any cellular context.
4. The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed supra) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that either compound, BMF-1-64 or BMF-1-141, could be predictably used to reduce the level of any cellular component in any cellular context.
Genentech Inc. vs. Nova Nordisk states, "[A] patent is not a hunting license. It is not a reward for a search but a compensation for its successful conclusion and 'patent 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" (42 USPQ 2d 1001, Fed. Circuit 1997). A review of the state of the art fails to reveal the mechanism of action or experimental data regarding reducing the level of any cellular component in any cellular context. Determining if any particular claimed compound would reduce the level of any cellular component in any cellular context would require synthesis of the compound, formulation into a suitable dosage form, and subjecting it to clinical trials or to testing in an assay known to correlate to clinical efficacy of such treatment. As noted in supra, even in vitro and in vivo assays do not always correlate to efficacy in humans and are not generally predictive of clinical efficacy. This is undue experimentation given the limited guidance and direction provided by Applicants.
Accordingly, the inventions of claims 135-142 and 145-152 do not comply with the scope of enablement requirement of 35 U.S.C 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 139 and 149 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 139 and 149 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are: The instant claims recite “composition of claim… or a salt thereof”, but it is unclear what the relationship between “composition” and “a salt thereof” is.
Double Patenting
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 133-152 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15, 33, 44, 76 and 79 of prior U.S. Patent No. 11,666,661 B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 133-152, the compound in claim 33 of ‘661 reads on the compound of instant claim 133. The compound in claim 76 of ‘661 reads on the compound of instant claim 143. The pharmaceutical composition comprising a compound and pharmaceutical excipient in claim 79 of ‘661 reads on the pharmaceutical composition of instant claims 134 and 144. The recitation “a monovalent cellular component binder covalently bound to a monovalent targeted autophagy protein binder” in claims 15 and 44 of ‘661 refers to an application to target autophagy protein and thus a method that reads on instant claims 135, 139, 145, and 149. Instant claims 136-138, 140-142, 146-148, and 150-152 are the consequences after contacting a cellular component with the claimed compound or composition, and thus are intended results, not structural limitations.
Conclusion
Claims 133-152 are rejected.
No claim is allowed.
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/C.L.J./Examiner, Art Unit 1691
/YIH-HORNG SHIAO/Primary Examiner, Art Unit 1691