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 .
Receipt of claim amendments and arguments filed on July 20, 2026 is acknowledged. Claims 25-26 have been added. Claims 1-5, 7, 10-11, 14-15, 18, 21 and 25-26 are now pending.
Applicant previously elected Group I, claims 1-9, drawn to methods of use of compounds of Formula I
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, and species compound
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, in the reply filed on January 19, 2026 is acknowledged. Claims 1-5 and 7 read on the elected species.
Claims 10-11, 14-15, 18, 21 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/19/2026.
Examination
Rejections and objections not reiterated herein have been withdrawn in view of the amendments and/or convincing arguments.
The claims examined have been amended to a method of treating cancer characterized by overexpression of PD-L1 comprising administering a compound of Formula I. The scope of Formula I has also been amended.
The elected species
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was searched and no applicable prior art was identified. The search has not been expanded further from that in the prior Office action. The prior art search will not be extended unnecessarily to cover all non-elected species. Subject matter outside of the searched/examined scope and claims 10-11, 14-15, 18, 21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions there being no allowable generic or linking claim.
Claims 1-5, 7, 25 and 26 are the subject of this Final Office Action.
The claim amendments have necessitated the new grounds of rejection presented in this Final Office Action.
Claim Rejections - 35 USC § 112
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 1-4, 7 and 26 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 pre-AIA the applicant regards as the invention.
Regarding claim 1, the phrase "A and B, if present" for the moiety
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renders the claim indefinite because X is a nitrogen atom, and a nitrogen atom with only one bond cannot exist. This rejection can be overcome by removing “, if present,”.
The dependent claims are rejected for containing the issues of claim 1.
Claim Rejections - 35 USC § 112
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 1-5, 7 and 26 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. This is a written description rejection.
First, it is noted that compound 47
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is not encompassed by Formula I. Formula I differs in that X is a nitrogen atom (not sulfur) and the -C(O)-CH2-S-Hy group is attached to position 2 of the phenanthrene ring while Formula I requires it to be at the 3-position.
The invention is in a class of inventions which the CAFC has characterized as "the unpredictable arts such as chemistry and biology." Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001). In addition, the state of the art is that “chemical reactions are known as unpredictable”. In re Marzocchi, et al., 169 USPQ 367, 370 (CCPA 1971); In re Fisher, 166 USPQ 18, 24 (CCPA 1970). Hence, the need for greater disclosure.
To satisfy the written description requirement, a specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319 (Fed. Cir. 2003). Where, as here, the claims cover a broad genus, 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.” AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not 36 supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of the genus.”).
In applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938).
In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). A need for greater disclosure derives from the fact it is not obvious from the disclosure of one species, what other species will work. Generally speaking, then, the Courts recognize that predictability in chemical arts is low enough to require a highly detailed disclosure. Unpredictability arises in chemical arts because subtle changes in molecular structure may greatly impact a compound's structure-activity relationship, pharmacologic activity, and/or biologic profile. In drug development, the skilled artisan would not be able to easily extrapolate the biological activity from a single example or limited disclosure without more instruction. These considerations support a requirement for a disclosure with a high level of detail.
“The examples and description should be of sufficient scope as to justify the scope of the claims”. See MPEP § 608.01(p). If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, para. 1 (MPEP 2163).
The rejected claims are drawn to a method of treating cancers characterized by overexpression of PD-L1 comprising administering a compound represented by Formula I
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, wherein Y is O or S, X is N, R1 through R11 are each independently selected from hydrogen, alkyl, cycloalkyl, alkoxy, and halo,
and
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The genus encompasses a substantial number of different embodiments of compounds and cancers.
In the instant case, the specification only describes compound species #69
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to support the whole genus of compounds of Formula I for treating cancers characterized by overexpression of PD-L1. This one operative species is not a representative sample of the claimed genus.
MPEP 2163 states that "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)”. The Federal Circuit has explained that a specification cannot always support expansive claim language and satisfy the requirements of 35 U.S.C. 112 "merely by clearly describing one embodiment of the thing claimed." LizardTech v. Earth Resource Mapping, Inc., 424 F.3d 1336, 1346, 76 USPQ2d 1731, 1733 (Fed. Cir. 2005). The issue is whether a person skilled in the art would understand applicant to have invented, and been in possession of, the invention as broadly claimed.
In particular, the specification shows that Applicant selected 94 hit compounds from virtual screening and molecular docking techniques from a library of over 900k compounds. Biochemical binding assays were then performed on the 94 selected compounds and 16 of them were found to inhibit binding to PD-L1. Only one representative compound of Formula I (compound 69), and one other compound with the phenanthrene scaffold (compound 47), were validated to inhibit PD-L1. Seven phenanthrene compounds were removed from the final screening; their structures not disclosed in the specification. The specification does not identify structural, chemical, physical or other characteristics that distinguish the operative embodiments from the non-operative embodiments. The evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.
The record affirmatively demonstrates that the claimed genus contains substantial variation in operative behavior, including embodiments that fail to exhibit the claimed behavior. Embodiments that fail to exhibit the claimed behavior are those that Applicant did not proceed with validation and were removed from the screening (seven phenanthrenes), because they failed to satisfy applicant’s own criteria for the selection of inhibitors based on docking, pocket complementarity and ADMET properties. (See Applicant’s remarks at page 13-14.)
Accordingly, the one disclosed embodiment does not constitute a representative sampling of the claimed genus. Rather, the disclosure demonstrates substantial variation among the embodiments encompassed while providing insufficient information from which a person of ordinary skill in the art could recognize which compounds are indeed inhibitors of PD-1/PD-L1. In particular, the specification fails to establish a sufficient structure-function correlation that would permit a person of ordinary skill in the art to recognize which members of the claimed genus possess the claimed function.
The problem is particularly significant here also in view of the teachings of the prior art. The prior art Field et al. showed that, changing the alkyl group attached to the nitrogen atom from dioctyl, dihexyl or diamyl to dietyl, dipropyl and dibutyl, on phenanthrene alkylamine compounds, made the analogs inactive in cancer. Likewise, when an active dihexylamino-phenanthrene analog was changed to dimethylamino-, dibutylamino-, diamylamino-, and dinonylamino-, these analogs were inactive in treating the cancers. See the second paragraph and page 412 in Field et al.
Without a sufficient representative number of operative species or identifying characteristics that correlate with the claimed function, a skilled artisan would have no reasonable basis for recognizing that Applicant had possession of the entire claimed genus at the time of filing.
In addition, the specification of this application does not describe any manner and process of making the genus of compounds of Formula I or any particular species.
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"). Accordingly, it is deemed that the specification does not describe in sufficient detail the genus of compounds in the claims, how to make them and how to use them as generally claimed, and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Applicant’s arguments have been carefully considered but were found unpersuasive.
Applicant argues that the instant application does not merely disclose an isolated compound, rather a comprehensive structure-based discovery program in which about 900,000 compounds were computationally screened, 94 virtual hits were identified, multiple compounds were experimentally validated, and representative compounds sharing common structural characteristics were selected for further biological evaluation of the PD-1/PD-L1 pathway. In response, while applicant may have performed computational screening and testing of various compounds, only a single phenanthrene alkylamine species was tested and disclosed as inhibitor of PD-L1 for the genus of Formula I. The tests for all other compounds that do not share common structural characteristics with Formula I are irrelevant.
Applicant further argues that the seven additional phenanthrene compounds that were removed from the screening, were removed merely on the basis of docking score, pocket complementarity, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties. In response, this shows that the seven compounds removed from the testing didn’t satisfy Applicant’s own criteria for PD1/PD-L1 inhibition.
The specification does not disclose a sufficient number of representative operative species spanning the variation in the genus, nor does it disclose a reliable structural or functional characteristic that distinguishes the operative embodiments from the inoperative embodiments.
Applicant argues that the hit compounds were obtained from a catalogue collection and that the compounds encompassed by amended Formula I are based on conventional phenanthrene chemistry employing well-known substituent classes and functional groups routinely used in medicinal chemistry without requiring special expertise and inventive effort. However, 35 U.S.C. 112(a) requires that the specification contains a description of the manner and process of making the genus of compounds of Formula I, which is not contained in the specification. The lack of a preparation method in the original disclosure, or even references describing how the compounds could be made, demonstrates that Applicant was not in possession of the whole claimed genus.
In the instant case, the disclosure regarding inhibitors of PD-L1 of Formula I amounts at most to identification of an individual catalogue compound (compound #69), rather than a description of the full claimed genus.
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) 1-5 and 7 are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by Field et al. (Cancer Research (1959), 19(No. 10, Pt. 2), 409-428-provided by Applicant in the IDS of 07/30/2025).
This rejection is maintained because renal cancer (RC carcinoma) is known to overexpress PD- L1/PD-1, per the original specification at page 15.
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The prior art teaches experimental procedures in which phenanthrene derivatives were administered to mice with Crocker Sarcoma 180 and RC carcinoma. See page 410.
Compounds
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and others, were administered to mice with Crocker Sarcoma 180 and RC (renal cell) carcinoma. Administration of compound SC 4163 to mice with cancer showed an average reduction tumor size of 21%, and compound SC 2131 showed an average reduction tumor size of 18%. See Table II at pages 421-422. This anticipates a method of treating a cancer overexpressing PD-L1/PD-1 (renal carcinoma) in a subject in need thereof (mice), comprising administering to the subject a therapeutically effective amount of a compound of Formula I. The amount of the compound administered was effective to reduce tumor size in the mice.
Applicant’s arguments were carefully considered but were found unpersuasive. Applicant argues:
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In response, the evidence shows that renal carcinoma tumors overexpress PD-L1. Field also taught that the compound claimed was administered to mice having said RC carcinoma tumors that overexpress PD-L1.
The administration of the prior art’s composition, which is the same as claimed, to the prior art subjects, which are the same as claimed, would have necessarily achieved the claimed method of treating the cancer that is characterized by overexpression of PD-L1 (renal cancer), even if not recognized by the prior art, since products of identical chemical composition cannot have mutually exclusive properties when administered under the same circumstances, or, as in the present case, to the same host. Thus, the identical compound administered to the identical subject under the identical circumstances must have the same claimed result. See MPEP 2112: “There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference.”
Applicant argues that the selection of patients suffering from cancers characterized by overexpression of PD-L1 is not an arbitrary patient subgroup. In response, mice with RC cancer that were treated in the experiments of Field are patients suffering from renal cancer which is characterized by overexpression of PD-L1, as required by the instant claims.
Conclusion
Claims 1-5, 7 and 26 are rejected. Claim 25 is objected to for depending of a rejected claim.
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 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 VALERIE RODRIGUEZ-GARCIA whose telephone number is (571)270-5865. The examiner can normally be reached Monday-Friday 9:30am-5:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/VALERIE RODRIGUEZ-GARCIA/ Primary Examiner, Art Unit 1621
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