DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 14-32 are pending. Claims 1-13 and 33 are cancelled.
Status of Priority
The present application is a CON of U.S. Application No. 15/769,565, filed on April 19, 2018 and issued as US 11,459,295, which is a 35 U.S.C. § 371 national stage patent application of International patent application PCT/US2016/058075, filed on October 21, 2016, which claims benefit of priority to U.S. Provisional Application no. 62/244,934, filed on October 22, 2015.
Specification - Disclosure
The disclosure is objected to because of the following informalities:
On pg. 59 of the clean copy of the specification (dated 02/18/2026) in Example 4, Table 2, Naproxen is referred to as compound 1a and R-naproxen is referred to as compound 9 yet in Table 1 of the specification (see pg. 57), compound 1a corresponds to R-naproxen and compound 9 corresponds to dimethylnaproxen.
Please amend the specification to ensure consistent identification and labeling of compounds throughout the disclosure.
Appropriate correction is required.
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Election/Restrictions
As a reminder, the Office has previously restricted the pending claims into two groups:
Group I: Claims 1-13, drawn to a compound of formula (I) and
Group II: Claims 14-19, drawn to a method of using a compound of formula (I).
Claims 1-13 are now cancelled and only claims 14-32, which corresponds to Group II, remain. As such, Applicant elected, without traverse, Group II. Applicant also elected the following species without traverse:
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and indicated that claims 14-19 read on the elected species.
Examiner previously stated:
Claims 14-31 read on Applicant's species election and are under examination in accordance with the MPEP 803.02. The claimed methods of using the elected species are allowable in view of the prior art; therefore, examination of the Markush-type claim has been extended to the scope of formula (I) wherein, R₁ is OH or C1 alkoxy, R₂ and R₃ are selected from H and C1 alkyl, and R4 is C2-alkyl, C1-C2 alkoxy or -S(C1 alkyl).
In view of Applicant remarks dated February 18, 2026 and an additional prior art search, Examiner has found the claimed methods to be novel and nonobvious.
Withdrawn Rejections
Applicant is notified that any outstanding rejection or objection that is not expressly maintained in this office action has been withdrawn or rendered moot in view of applicant’s amendments and/or remarks.
Claim Objections
Claim 30 is objected to because of the following informalities:
For consistency, claim 30 should read:
“The method of claim 20, wherein the compound of formula (I) is selected from the group consisting of…”
Appropriate correction is required.
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 14-32 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:
A method of treating or ameliorating a prostate cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of at least one compound of formula (I):
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wherein:
R1 is as defined in claim 14 EXCEPT for the option of alkyl, alkoxy or cycloalkoxy group being optionally substituted with an optionally substituted aryl,
R2, R3, and R4 are as defined in claim 14,
wherein the compound is not a compound wherein R1 is OH, one of R2 and R3 is methyl and the other is H, and R4 is methoxy, and
wherein the compound exists in racemic form;
The method of point A, further comprising the limitation recited in claim 15;
The method of point A, wherein at least one of (a), (b), or (c) (as recited in claim 16) applies;
A method of inhibiting aldo-keto reductase family 1, member C3 (AKR1C3) in a mammalian cell, the method comprising contacting the cell with an effective amount of at least one compound of formula (I):
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wherein:
R1 is as defined in claim 17 EXCEPT for the option of alkyl, alkoxy or cycloalkoxy group being optionally substituted with an optionally substituted aryl,
R2, R3, and R4 are as defined in claim 17,
wherein the compound is not a compound wherein R1 is OH, one of R2 and R3 is methyl and the other is H, and R4 is methoxy, and
wherein the compound exists in racemic form;
The method of point D, with the limitations of claim 18;
The method of point D, with the limitations of claim 19;
A method for treating benign prostatic hyperplasia, the method comprising administering to the subject a therapeutically effective amount of at least one compound of formula (I), or a salt or solvate thereof:
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wherein:
R1 is as defined in claim 20 EXCEPT for the option of alkyl, alkoxy or cycloalkoxy group being optionally substituted with an optionally substituted aryl,
R2, R3, and R4 are as defined in claim 20,
wherein the compound is not a compound wherein R1 is OH, one of R2 and R3 is methyl and the other is H, and R4 is methoxy, and
wherein the compound exists in racemic form, or wherein the compound is the (R)-enantiomer and is free of the corresponding (S)-enantiomer;
H through R) The method of G, with the limitations of claims 21 through 31, respectively;
does not reasonably provide enablement for elements that are outside the scope of the enabling elements listed above. 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.
As stated in the MPEP 2164.01(a), “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.”
In evaluating the enablement question, several factors are to be considered. According to In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988), these factors include:
1) The nature of the invention,
2) the state of the prior art,
3) the predictability or lack thereof in the art,
4) the amount of direction or guidance present,
5) the presence or absence of working examples,
6) the breadth of the claims, and
7) the quantity of experimentation needed to make and use the invention based on the content of the disclosure, and
8) the level of the skill in the art.
In the instant case, the Wands factors are relevant for the following reasons:
The nature of the invention
The nature of the invention claims 2-β-naphthyl-acetic acid derivatives that are compounds of the following general formula (I):
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which are selective AKR1C3 inhibitors. The variables of general formula (I) are defined in instant claim 1. In certain embodiments, the compounds of the invention are R-naproxen analogs. The invention further includes methods of treating cancer, such as prostate cancer and/or castration-resistant prostate cancer, using at least one compound of the invention.
State of the prior art
Prior art referenced:
Steele et al. (Steele) (Steele, V. E. et al. Chemopreventive Efficacy of Naproxen and Nitric Oxide–naproxen in Rodent Models of Colon, Urinary Bladder, and Mammary Cancers. Cancer Prev Res 2009, 2, 951-956.)
Steele teaches that in the rat colon aberrant crypt foci model and the rat urinary bladder cancer model, significant inhibition in tumor growth was observed when the rats were administered naproxen (abstract).
However, in the mammary cancer model in rats, nonsignificant inhibitions were observed when the rats were administered naproxen (abstract).
Therefore, the data disclosed by Steele show that naproxen (i.e., reference compound 1 in the instant specification) are effective agents against urinary bladder and colon, but not mammary, carcinogenesis (abstract, last sentence).
Andrews et al. (Andrews) (Andrews, J. et al. Superior effectiveness of ibuprofen compared with other NSAIDs for reducing the survival of human prostate cancer cells. Cancer Chemother Pharmacol 2002, 50, 277-284.)
Although ibuprofen exhibits superior effectiveness in reducing the survival of human prostate cancer cells (see abstract), all NSAIDs tested (which includes naproxen) resulted in a significant reduction in proliferation of LNCaP cells (i.e., a human prostate cancer cell line) (see pg. 278, 1st paragraph of “Results” section and Fig. 1).
Additionally, naproxen induced 100% apoptosis at 5 mM (see Fig. 2).
Yin et al. (Yin) (Yin, Y. D. et al. The Activity of SN33638, an Inhibitor of AKR1C3, on Testosterone and 17β-Estradiol Production and Function in Castration-Resistant Prostate Cancer and ER-Positive Breast Cancer. Front. Oncol. 2014, 4, 159.)
The results of Yin suggests that “inhibition of AKR1C3 is unlikely to produce therapeutic benefit in CRPC [i.e., castration-resistant prostate cancer] and ER-positive [i.e., estrogen receptor-positive] breast cancer patients, except possibly in the small subpopulation of CRPC patients with tumors that have upregulated AKR1C3 expression and are dependent on AKR1C3 to produce the testosterone required for their growth” (abstract, last sentence).
The level of the skill in the art
The level of ordinary skill in the art is relatively high. A person of ordinary skill would typically have formal training in oncology and/or medicinal chemistry as well as organic synthesis and would be familiar with standard methods for evaluating therapeutic efficacy of compounds.
The presence or absence of working examples
The instant specification only provides the following working examples:
Example 1: AKR1C3 and AKR1C2 inhibitor screening of compounds 2-10.
Compounds 1 and 1a (i.e., S-Naproxen and R-Naproxen, respectively) are not encompassed by the formula recited in the claims.
Example 2: Effect of compound 8a and 8b on AKR1C2 catalyzed reduction of 5α-DHT
Example 3: Mode of AKR1C3 inhibition by compound 8a
Example 4: Inhibition of COX-1
Only provides AKR1C3, COX-1, and COX-2 inhibition data for compounds 8a and 8b.
Example 5: Effect on AR reporter gene assay
Only evaluated compound 8a
Example 6: Inhibition of AKR1C3-mediated production of testosterone with compound 8a
Example 7: Inhibition of AKR1C3 mediated AR gene expression with compound 8a
Example 8: Synthetic procedure
It is noted here that besides instant example 1, all the other instant examples only involved testing compound 8a and 8b or only compound 8a.
The breadth of the claims
The claims are broad insofar as the instant claims recite a compound of general formula (I) wherein the compound can possess a structurally diverse range of chemical groups. In particular, R1 of general formula (I) may be selected from OH, -NHSO2(C1-C6 alkyl), C1-C6 alkoxy, or C3-C8 cycloalkoxy, wherein the alkyl, alkoxy or cycloalkoxy can be optionally substituted with an optionally substituted aryl. Since the claims do not place meaningful limitations on the substituents that may be present on the aryl group, the claims encompass a large number of structurally distinct compounds spanning a broad chemical genus.
Further, the claims are broad insofar as the instant claims recite a method of treating or ameliorating any cancer or any androgen-dependent proliferative disorder disease in a subject.
The amount of direction or guidance present;
the predictability or lack thereof in the art; and
the amount of direction or guidance present and the quantity of experimentation needed to make and use the invention based on the content of the disclosure
The amount of direction and guidance provided in the specification is limited relative to the breadth of the claimed subject matter. The claims encompass methods of treating or ameliorating any cancer and any androgen-dependent proliferative disorder or disease using compounds drawn from a broad chemical genus. However, the working examples primarily provide in vitro enzyme inhibition data demonstrating selective inhibition of AKR1C3 over AKR1C1 and AKR1C2, inhibition of testosterone formation, and inhibition of androgen receptor signaling. The specification does not provide working examples demonstrating efficacy across the broad range of cancers and androgen-dependent proliferative disorders encompassed by the claims.
The prior art further demonstrates that therapeutic efficacy is highly unpredictable. Steele teaches that naproxen (i.e., reference compound 1 in the instant specification) exhibited significant inhibitory activity in colon and urinary bladder cancer models, but failed to produce significant inhibition in a mammary cancer model. Thus, even for a compound sharing the same core scaffold as the instant compounds, activity in one cancer type does not reasonably predict activity in another cancer type. Andrews further teaches that naproxen can reduce proliferation of LNCaP prostate cancer cells, indicating that naproxen-derived compounds may possess activity in prostate cancer models. Taken together, these references demonstrate that anticancer activity is cancer-type dependent and cannot be reliably extrapolated across all cancers.
The unpredictability is further illustrated by Yin, which teaches that selective inhibition of AKR1C3 is unlikely to provide therapeutic benefit in most castration-resistant prostate cancer patients, except possibly in a limited subpopulation whose tumors are highly dependent on AKR1C3-mediated androgen biosynthesis. Thus, even within a disease state directly associated with AKR1C3 activity and is considered as an androgen-dependent proliferative disease, inhibition of the target enzyme is not reliably predictive of therapeutic efficacy. Accordingly, a person of ordinary skill in the art would not reasonably conclude from the disclosure that all compounds encompassed by the claims would be useful for treating all androgen-dependent proliferative disorders or cancers merely because they inhibit AKR1C3.
Because the specification provides experimental support for only a small number of compounds, primarily compounds 8a and 8b, a person of ordinary skill in the art would be required to engage in extensive experimentation to determine which members of the broadly claimed genus possess therapeutic activity. Such experimentation would include synthesizing large numbers of compounds having different substituent combinations, establishing structure-activity relationships for the broad range of optionally substituted aryl-containing embodiments encompassed by the claims, evaluating selectivity toward AKR1C3, and subsequently testing each candidate compound in relevant disease models to determine whether enzyme inhibition translates into therapeutic benefit. In view of the limited guidance provided by the specification and the unpredictability demonstrated in the prior art, the amount of experimentation required to identify therapeutically effective compounds across the full scope of the claims would constitute undue experimentation.
Written Description
Claims 14-32 are 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.
According to MPEP § 2163:
“Satisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’ Such correlations may be established ‘by the inventor as described in the specification,’ or they may be ‘known in the art at the time of the filing date.’ See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014).
In the present case, the claims encompass a broad genus of compounds of formula (I) in which multiple variables may independently assume numerous alternative substituents. In particular, R1 may comprise alkyl, alkoxy or cycloalkoxy groups that are optionally substituted with optionally substituted aryl groups, while the claims do not limit the nature of the substituents that may be present on the aryl moiety. Accordingly, the claims encompass a very large number of structurally distinct compounds possessing substantially different steric, electronic, and physicochemical properties.
The instant specification does not provide a representative number of species commensurate with the breadth of the claimed genus. Although a limited number of compounds are synthesized and evaluated, the biological studies are focused primarily on compounds 8a and 8b, with the majority of the functional data generated using compound 8a. The disclosure therefore demonstrates possession of only a narrow subset of the compounds encompassed by the claims (specifically those as enumerated in the “Scope of Enablement” section above in points A through R) and does not adequately describe the full structural diversity of the claimed genus.
The functional scope of the claims is likewise exceedingly broad. The claims encompass methods of treating or ameliorating any cancer as well as any androgen-dependent proliferative disorder or disease. However, the specification provides only in vitro data relating to selective AKR1C3 inhibition over AKR1C1 and AKR1C2, inhibition of testosterone formation, and inhibition of androgen receptor signaling. The instant specification does not provide representative examples demonstrating treatment across the broad range of cancers encompassed by the claims, nor does it provide representative examples demonstrating treatment across the broad range of androgen-dependent proliferative disorders encompassed by the claims.
The lack of representative species is particularly significant in view of the unpredictability of the art. As discussed above in the “Scope of Enablement – 2. State of the prior art” section, Steele demonstrates that naproxen (i.e., a compound sharing the same core scaffold as the compounds of the instant invention) exhibited activity in certain cancer models but not in others. Andrews further demonstrates activity of naproxen in prostate cancer cells, while Yin teaches that selective inhibition of AKR1C3 is unlikely to provide therapeutic benefit in most castration-resistant prostate cancer patients (i.e., patients with a type of androgen-dependent proliferative disease), except possibly in a limited subpopulation whose tumors are highly dependent on AKR1C3-mediated androgen biosynthesis. These references illustrate that neither structural similarity to naproxen nor inhibition of AKR1C3 reliably predicts therapeutic efficacy across all cancers or all androgen-dependent proliferative disorders.
Therefore, the mere disclosure of in vitro enzyme inhibition data, without corresponding evidence demonstrating therapeutic activity in representative disease models, does not reasonably convey to a POSITA that the inventors were in possession of methods for treating the full scope of the claimed diseases. For example, the specification does not provide representative data demonstrating inhibition of cancer cell proliferation, induction of apoptosis, reduction of tumor growth, or other evidence of therapeutic efficacy across the broad range of cancers and androgen-dependent proliferative disorders encompassed by the claims.
Accordingly, the disclosure does not reasonably convey to a POSITA that the inventors were in possession of the full scope of the claimed methods. Instead, the disclosure supports a limited subset of compounds and a limited subset of disease indications. Since the specification fails to provide a representative number of species or other identifying characteristics sufficient to demonstrate possession of the full claimed genus, the claims lack adequate written description.
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 14-21, 24-27, 29, and 32 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.
The term “significantly” in claim 18 is a relative term which renders the claim indefinite. The term “significantly” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably ascertain the scope of the invention. Although the specification and the claim itself attempts to provide guidance by stating that the contacting may inhibit less than about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% of AKR1C1 and/or AKR1C2, these disclosures do not resolve the ambiguity. Instead, the specification indicates that “not significantly inhibit” may encompass inhibition levels ranging from less than 5% (essentially no inhibition) to less than about 95% inhibition (near-complete inhibition). As a result, the specification associates the phrase “not significantly inhibit” with a broad range of substantially different inhibition levels, including levels that a POSITA would reasonably consider as significant inhibition.
Accordingly, neither the claims nor the specification provide a clear boundary for determining when inhibition of AKR1C1 and/or AKR1C2 becomes “significant.” Therefore, claim 18 is rendered indefinite.
Claims 14, 17, 20, and 21 recites “optionally substituted” without specifying what substituents are encompassed. Neither the claim nor the specification discloses the types of substituents encompassed, the permissible number of substituents, or the positions at which substitution may occur. Therefore, it is unclear what chemical structures are encompassed by the term “optionally substituted” as the term could include an unlimited range of functional groups and substitution patterns, including those that would significantly alter the chemical and physical properties of the claimed compound. As such, a POSITA would not be able to determine the metes and bounds of the claimed invention with reasonable certainty and claims 14, 17, 20, and 21 are rendered indefinite.
Claims 15 and 16 (which are dependent on claim 14), claims 18 and 19 (which are dependent on claim 17) and claims 24-27, 29, and 32 (which are dependent on claim 20), are also rejected for further requiring and/or reciting the indefinite limitation of claims 14, 17, and 20.
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 14-31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over:
claims 1-17 of U.S. Patent No. 11,459,295 (‘295)
Although the claims at issue are not identical, they are not patentably distinct from each other because ‘295 patent discloses compounds of formula (Ia):
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(wherein R2 is ethyl, and R1 and R4 are the same as instantly claimed), and methods of treating/ameliorating prostate cancer as well as a method of inhibiting aldo-keto reductase family 1, member C3 (AKR1C3) in a mammalian cell, which fall within the scope of the instantly claimed methods of:
treating/ameliorating cancer,
treating an androgen-dependent proliferative disorder or disease, and
inhibiting aldo-keto reductase family 1, member C3 (AKR1C3) in a mammalian cell
as explained in further detail below.
Claims 10-13 of ‘295 are encompassed by instant claims 14-16 and 20-31 and claims 14-17 of ‘295 are encompassed by instant claims 17-19. Specifically, the cancer/androgen-dependent proliferative disease (i.e., prostate cancer) and the genus of compounds recited in the claims of ‘295 are within the scope of the instant claims. Even though the instant claims specifically require administration of a racemic mixture of the recited compounds instead of administering only the R-enantiomer form, a POSITA would still have found it obvious to try and administer a racemic mixture of a compound of formula (I) in place of the isolated R-enantiomer of the compound, absent a showing of unexpected results attributable to the presence of the S-enantiomer. The instant specification and the specification of ‘295 teaches the R- and S- enantiomers of compound 8, for instance. A POSITA would therefore have reasonably expected that a racemic mixture containing the patented R-enantiomer would retain at least some of the activity associated with administration of the R-enantiomer alone. This is confirmed in instant Table 1: compound 8 (i.e., racemic mixture comprising of 8a and 8b) has AKR1C3 and AKR1C2 inhibition activity that more closely resembles compound 8b.
It is also noted here that instant claims 20-31 also expressly encompass embodiments wherein the administered compound is the isolated (R)-enantiomer of instant formula (I) with claims 29-31 explicitly requiring the compound to be in the (R)-enantiomeric form. Thus, for these claims, the administered compound may be identical to or encompassed by the compound recited in ‘295. The patented claims include claims directed to a method of treating or ameliorating prostate cancer by administering the (R)-enantiomer of formula (Ia). Instant claims 20-31 encompass administration of the same (R)-enantiomer (either in a racemic mixture or in pure form) and recite treatment of an androgen-dependent proliferative disorder or disease which includes prostate cancer. Accordingly, the instant claims encompass the very embodiment of treating prostate cancer by administering the same (R)-enantiomer recited in the patented claim. A POSITA would have found it obvious to employ the same (R)-enantiomer in the treatment of androgen-dependent proliferative disorder or disease, particularly since the specification of ‘295 itself identifies prostate cancer as a proliferative disease that is androgen dependent and intended to treat the prostate cancer by administering compounds encompassed by instant formula (I) to patients in need thereof (see ‘295, col. 8, lines 11-15).
Conclusion
No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTEN ROMERO whose telephone number is (571)272-6478. The examiner can normally be reached M-F 9:30 AM - 6:00 PM ET.
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/KRISTEN W ROMERO/Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
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