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
Filing Receipt and Priority
The filing receipt mailed 06/20/2024 states the instant application is a 371 of PCT/US2021.062777, filed 12/10/2021, which claims benefit of provisional application 63/124,503, filed 12/11/2020.
The instant application finds support in the provisional application. Therefore the effective filing date is 12/11/2020.
Information Disclosure Statement
As of the date of this action, no information disclosure statement (IDS) has been submitted.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Rejections
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.
Scope of Enablement
Claims 2 and 17 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 the treatment of hirsutism, hypertrichosis, and unwanted hair does not reasonably provide enablement for chemotherapy-related hair loss, radiation-related hair loss, and combinations of the conditions. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The following Wands factors have been considered if not explicitly discussed.
(A) The breadth of the claims, (B) The nature of the invention, (C) The state of the prior art, (D) The level of one of ordinary skill, (E) The level of predictability in the art, (F) The amount of direction provided by the inventor, (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Breadth of the claims
Claim 2 claims a method of treating hirsutism, hypertrichosis, unwanted hair, chemotherapy-related hair loss, radiation-related hair loss, and combinations of said conditions by administering compounds of structures of formula I.
Claim 17 claims a method of treating hirsutism, hypertrichosis, unwanted hair, chemotherapy-related hair loss, radiation-related hair loss, and combinations of said conditions by administering compounds of structure of formula II.
Compounds of formula I and II
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State of the prior art
Regarding claim 2, the closest art is found in deLong (US 2018/0064622). deLong teaches methods of inhibiting hair growth and/or treating hirsutism and hypertrichosis comprised of administering a compound of structure shown below.
deLong compound
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deLong discloses that the compound above is an effective FP antagonist. Similar FP antagonists are found in Page and Lamers (see 103 rejection below).
None of deLong, Page, or Lamers discuss methods of treating chemotherapy- or radiation-related hair loss. None of the cited references discuss how FP antagonism would treat hair loss, much less chemotherapy- or radiation-related hair loss.
Regarding claim 17, a compound that embraces formula II is disclosed in Beck (J. Med. Chem. 2020, 63, 11639-11662, published September 24, 2020). Beck discloses the compound as an FP antagonist that has efficacy in treating lung fibrosis.
The instant disclosure points to Beck (US2020/0157073, herein after Beck ’073). Beck ‘073 discloses the compound of claim 20, which embraces formula II, in para. [1730]. While Beck ‘073 in para. [0193] contemplates the compound as suitable for hirsutism or hypertrichosis, it does not disclose any specific method of treating hirsutism or hypertrichosis. Beck ‘073 in para. [0193] states “the compounds of the invention can also be used for the treatment of disorders of the female reproductive system, such as uterine myoma…In addition, they are suitable for prophylaxis or treatment of hirsutism or hypertrichosis.”
The closest that the cited art gets to connecting FP receptor antagonism to hair growth or hair loss is in Beck ‘073, para. [0010] where it states “The PGF2 receptor (FP) is involved in joint disorders and the regulation of the signal cascade of the bone morphogenetic protein (BMP)…More stable analogues of PGF2α have been developed for oestrus synchronization and for influencing human reproductive functions and also for reduction of intraocular pressure for treatment of glaucoma. In the latter application, a side-effect that was observed was the stimulation of hair growth…”. However, this is insufficient to enable the instant disclosure.
Amount of direction and guidance
The instant specification discloses no examples of the compounds of claims 2 and 17 in methods of treating any of the conditions stated above. The instant disclosure relies on the art (deLong and Beck ’073) to enable the disclosure for methods of treating hirsutism, hypertrichosis, and unwanted hair growth.
Level of predictability
Considering the lack of working examples and the lack of publicly available information, there would have been a significant level of unpredictability at the time of the effective filing date should one of ordinary skill had attempted to practice the instantly claimed methods towards treating chemotherapy- or radiation-related hair loss and/or combinations of the conditions claimed.
Written Description
Claims 2 and 17 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 2 and 17 state the following: A method of treating a condition…wherein the condition is selected from at least one of hirsutism, hypertrichosis, unwanted hair, chemotherapy-related hair loss, radiation-related hair loss, and a combination thereof.”
Of the conditions listed, treating hair loss (i.e. promoting hair growth) runs opposite to treating hirsutism, hypertrichosis, and unwanted hair (inhibiting hair growth).
No where within the instant specification or within the art is there discussion that would indicate to one of ordinary skill in the art that both promoting hair growth and inhibiting hair growth can be achieved simultaneously.
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.
Claim 18 is 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.
Claim 18 recites the limitation “Rc and Rd together with the nitrogen to which they attach form a saturated or partially unsaturated 5- to 7-membered monocyclic or 7- to 10-membered bicyclic heterocyclic ring,…wherein the heterocyclic rings are optionally substituted with 1-2 substituents independently selected from the group consisting of…CHF2, CF3, CH2CHF2, and CH2CF3, and optionally substituted with 1-4 fluoro…”.
Claim 18 is dependent upon claim 16 which states “Rc and Rd together with the nitrogen to which they attach form a saturated or partially unsaturated 4- to 8-membered monocyclic or 6- to 10-membered bicyclic heterocyclic ring,…wherein the heterocyclic rings are optionally substituted with 1-4 substituents independently selected from the group consisting of…C1-4alkyl substituted with 1-5 fluoro…”.
The “optionally substituted” limitation in claim 18 would cause certain substituents to exceed the max allowable number of fluorine atoms on the substituent. This contradiction would cause one of ordinary skill in the art to not know the metes and bounds of the claims.
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.
Claim(s) 16-20 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Beck (J. Med. Chem. 2020, 63, 11639-11662, published September 24, 2020).
Claim 16 states “A method of inhibiting hair growth, the method comprising administering to a subject in need thereof, a safe effective amount of a compound of formula (II), or a pharmaceutically acceptable salt thereof.”
Claim 17 states “A method of treating a condition, the method comprising administering to a subject in need thereof, a safe an effective amount of a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein the condition is selected from at least one of hirsutism, hypertrichosis, unwanted hair, chemotherapy-related hair loss, radiation-related hair loss, and a combination thereof…”.
The general structure formula II and a specific claimed compound are shown below
Compound of formula II and claim 20 compound
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(claimed compound)
Beck on p. 11640, right col., para. 3 states “OBE022 is the only hFP-R antagonist currently in active clinical development, for the treatment of preterm labor.” Beck continues and states “Herein, we present our research toward novel quinoline-based hFP-R antagonists, culminating in BAY-6672, showing a favorable overall compound profile including in vivo efficacy in preclinical pharmacological model of lung fibrosis.”
The structure of BAY-6672 is shown below.
BAY-6672
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Beck on p. 11649, Figure 3 discloses results of administering BAY-6672 to mice.
While the claims are drawn to methods of inhibiting hair growth and/or treating conditions related to excessive hair growth or hair loss associated to chemotherapy, the claims only require the administration of the claimed compounds in a safe and effective amount. As Beck discloses a method of administering BAY-6672, Beck embraces the limitations of claims 16-20.
Claim Rejections - 35 USC § 103
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.
The factual inquiries 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.
Claim(s) 1-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over deLong (US 2018/0064622) in view of Page (US 9,447,055, published 2016) and Lamers (Expert Opin. Ther. Patents, 2013, 23(1)).
Claim 1 states “A method of inhibiting hair growth, the method comprising administering to a subject in need thereof, a safe and effective amount of a compound of formula (I), or a pharmaceutically acceptable thereof…”
The compound of formula I is shown below.
Compound Formula I
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Claim 2 states “A method of treating a condition, the method comprising administering to a subject in need thereof, a safe an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein the condition is selected from at least one of hirsutism, hypertrichosis, unwanted hair, chemotherapy-related hair loss, radiation-related hair loss, and a combination thereof…”.
Specifically claim 15 states “wherein the compound of formula (I) is…” and gives two structures.
Claim 15 compounds
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deLong in its abstract states “A method for inhibiting hair growth in mammals using compositions containing FP receptor antagonists…The compositions can be applied topically to the skin and/or hair. The compositions can arrest hirsutism or hypertrichosis, reverse hirsutism and hyper trichosis, and further prevent hair growth. These compositions also be used to protect hair from chemical or radiation-induced alopecia or hair loss.”
deLong in para. [0047] states “The compositions [of this invention] comprises A) an FP receptor antagonist or a selective modifier of the FP ligand as described herein and B) a carrier. DeLong in para. [0048] states “Preferably, the FP receptor antagonist is an active ingredient formulated into a composition such as a pharmaceutical or cosmetic compositions….”
deLong in para. [0062] teaches an example compound (AS604872).
deLong compound AS604872
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deLong in para. [0152] identifies the compound above as an FP receptor antagonist. deLong in the same paragraph also states that the significantly reduces hair growth. deLong in para. [0155] further states “TWO FP receptor antagonists according to the invention (ANT1, ANT2) or placebo were applied daily to mice…ANT2 is the compound of Example 3…As shown in FIG. 1 both ANT 1 and ANT 2 at the appropriate dose-level, inhibiting hair regrowth at week 3 and week 4 as compared to the control group.” Figure 1 of DeLong is shown below.
Figure 1 deLong
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Note that difference between the DeLong compound and the instant compounds is the presence of a pyridine in the instant compound. This difference is addressed by Page.
Regarding claims 3-15 Page in col. 19 and 20 teaches the following compounds (I) and (II).
Page Compounds I and II
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Page in col. 20, Table 1 also discloses the IC50 values of compounds I and II.
Page Table 1
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Further, motivation to modify the composition of DeLong with the compounds of Page is found in Lamers.
Lamers on p. 50 sec. 2.2 states “Applied Research Systems ARS Holding N.V. published a patent in 2003, regarding thiazolidine carboxamide derivatives related to 11 and 12 as modulators of the FP receptor. The disclosed compounds are claimed to be used in the treatment of preterm labor. For pharmacological characterization they used a competitive binding assay on human FP receptor, functional assays measuring the inhibition of PGF2α to its receptor at concentrations below 10 μM and had IC50 values below 2 μM for the inhibition of IP3 synthesis…Exemplified are 11 (IC50 (IP3) = 0.185 μM, Ki = 0.065 μM) and 12 (IC50 (IP3) = 0.015 μM, Ki = 0.055 μM) which showed the highest activity within in vitro testing.” Note the structures of compounds 11 and 12 below.
Lamers compounds 11 and 12
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Lamers compound 12 is the Page compound II. Compound 12 shows similar if not better pharmacokinetic properties than Compound 11 (DeLong compound above). Additionally, not only does Lamers compound 12 show similar or improved properties, Page indicates that their compound I shows even better properties (lower IC50 value).
Page and Lamers indicate an improvement over the DeLong compound. Therefore, one of ordinary skill in the art would find it obvious to include the Page compounds I and II into a method for inhibiting hair growth and a method for treating a condition as in claim 2.
Therefore, it would have been prima facie obvious at the time of the effective filing date for one of ordinary skill in the art to have modified deLong with the teachings of Page and Lamers. One of ordinary skill in the art would have found motivation to make the modification as the IC50 values of Page compounds I and II are an improvement over the deLong compound.
Claim(s) 16-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Beck ’073 (US2020/0157073, published 05/21/2020) in view of deLong (cited above).
Claim 16 states “A method of inhibiting hair growth, the method comprising administering to a subject in need thereof, a safe and effective amount of a compound of formula (II), or a pharmaceutically acceptable thereof…”
Claim 17 states “A method of treating a condition, the method comprising administering to a subject in need thereof, a safe an effective amount of a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein the condition is selected from at least one of hirsutism, hypertrichosis, unwanted hair, chemotherapy-related hair loss, radiation-related hair loss, and a combination thereof…”.
Beck ‘073 in para. [1730] teaches compound of structure shown below.
Beck ‘073 compound
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Beck ‘073 in para. [2820]-[2823] teaches that the inhibitory IC50 against human FP receptor of the above compound is 0.032 μMol (see entry for Ex. No. 33).
Beck ‘073 in para. [0193] contemplates the compound as suitable for hirsutism or hypertrichosis.
Beck ‘073 does not specifically state “inhibiting hair growth.” This is addressed by deLong.
deLong in para. [0152] identifies a FP receptor antagonist. That shows efficacy in reducing hair growth. deLong in para. [0155] further states “TWO FP receptor antagonists according to the invention (ANT1, ANT2) or placebo were applied daily to mice…ANT2 is the compound of Example 3…As shown in FIG. 1 both ANT 1 and ANT 2 at the appropriate dose-level, inhibiting hair regrowth at week 3 and week 4 as compared to the control group.” This teaching establishes that FP receptor antagonists are effective in reducing hair growth.
Hirsutism and hypertrichosis are conditions associated with excessive and unwanted hair growth. Not only does Beck ‘073 state that the compound above would be suitable for hirsutism and hypertrichosis, Beck ‘073 also teaches that the same compound is an effective inhibitor of human FP receptor. deLong teaches that inhibitors of FP receptor are effective at inhibiting hair growth. Therefore, one of ordinary skill would find it obvious to apply the compound of Beck ‘073 towards inhibiting hair growth and/or treating hirsutism, hypertrichosis, and unwanted hair growth.
Therefore, it would have bene prima facie obvious at the time of the effective filing date for one of ordinary skill in the art to have applied, with a reasonable assumption of success, the compound of Beck ‘073 towards inhibiting hair growth and treating hirsutism, hypertrichosis, and unwanted hair growth via the teachings of deLong. One of ordinary skill in the art would have found motivation to apply the compound of Beck ‘073 as Beck ‘073 states the compound is suitable for treatment of hirsutism and hypertrichosis. One of ordinary skill would find additional motivation to apply the compound to inhibit hair growth as deLong teaches FP receptors are effective in inhibiting hair growth.
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 1-20 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11, 13, and 31 of copending Application No. 18/591,891 in view of deLong (US 2018/0064622) in view of Page (US 9,447,055, published 2016), Lamers (Expert Opin. Ther. Patents, 2013, 23(1)) and additionally in view of Beck (J. Med. Chem. 2020, 63, 11639-11662, published September 24, 2020).
Reference claim 1 states “A method of inhibiting hair growth, the method comprising administering to a subject a safe and effective amount of at least one FP receptor antagonist.”
Reference claim 5 includes the conditions as claimed in instant claims 2 and 17.
Reference claim 31 includes a compound of formula (III) below.
Reference compound formula III
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The compounds discussed in the 103 rejection over deLong, Page, and Lamers embrace the compound of formula (III). Therefore, for similar reasons, the instant claims are not obvious over the reference claims.
Additionally, Beck discloses the FP receptor antagonist BAY-6672. Therefore, the general methods comprising administering a FP receptor antagonist (reference claims 1 and 5) would also make obvious the instant claims when combined with the teachings of Beck.
This is a provisional nonstatutory double patenting rejection.
Examiner’s Comments
Beck (cited above) on p. 11640, right col., para. 3 states “OBE022 is the only hFP-R antagonist currently in active clinical development, for the treatment of preterm labor.” The structure of OBE022 is shown below.
OBE022
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However, Beck does not disclose “safe and effective” amounts of OBE022.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LUISALBERTO GONZALEZ whose telephone number is (571)272-1154. The examiner can normally be reached M-F 8:30-5:30.
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/L.G./Examiner, Art Unit 1624
/SUSANNA MOORE/Primary Examiner, Art Unit 1624