DETAILED ACTION
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 .
Application Status
Applicant’s amendment and response, submitted July 7, 2026, has been reviewed by the examiner and entered of record in the file. Claims 1 and 7 are amended.
3. Claims 16-19 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to the nonelected invention of Group II, without traverse, there being no allowable generic or linking claim.
4. Claims 1-13 are under examination and are the subject of this office action.
Previous Claim Rejections - 35 USC § 112(a)
5. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
6. Claims 1-11 and 13 remain 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 regarding the scope of compounds and alternatives according to the instant genus of Formula (I). The claims contain 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 rejection has been modified as a result of Applicant’s amendment to the claims.
7. In particular, support cannot be found for the full scope of compounds of Formula (I) as instantly recited by the claims.
8. The MPEP §2163 states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. In the case of chemical entities, Applicant's attention is further directed to Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089, 118 S. Ct. 1548 (1998), which notes that an adequate written description requires a precise definition, such as by structure, formula, chemical name, or physical properties, “not a mere wish or plan for obtaining the claimed chemical invention.” While the court recognizes that, “[i]n claims involving chemical materials, generic formulae usually indicate with specificity what the generic claims encompass” (Id.), it is also recognized that for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim and/or the genus must be sufficiently detailed to show that applicant was in possession of the claimed invention as a whole (see Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555 (Fed. Cir. 1991)). If a genus has substantial variance, the disclosure must present a sufficient number of representative species that encompass the genus in order to adequately describe the genus (i.e., the disclosure must describe a sufficient variety of species to reflect the variation within that genus). See MPEP § 2163. Otherwise, as stated by the court in Ariad Pharmaceuticals, Inc., v. Eli Lilly and Company (Fed. Cir. 2010), “a generic claim may define the boundaries of a vast genus of chemical compounds, and yet the question may still remain whether the specification, including original claim language, demonstrates that the applicant has invented species sufficient to support a claim to a genus.
9. The factors considered in the Written Description requirement are:
(1) level of skill and knowledge in the art,
(2) partial structure,
(3) physical and/or chemical properties,
(4) functional characteristics alone or coupled with a known or disclosed
correlation between structure and function, and
(5) the method of making the claimed invention.
10. Level of skill and knowledge in the art: The level of skill to practice the art of the instantly claimed invention is high and requires a variety of skills usually found in institutions and companies that employ highly trained and skilled scientists to carry out these tasks.
11. Partial structure; Physical and/or chemical properties; and Functional characteristics: The claims are drawn to a compound according to the broad genus of amended Formula (I):
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, or a salt thereof, and its pharmaceutical composition. In the instant case, it is evident that the genus of compounds embraced by Formula (I) has substantial variance. The claimed genus of Formula (I) is virtually without limit, embracing hundreds of thousands of compound species, and potentially millions of compound species, which bear little structural overlap with one another, e.g., presently the genus of compounds according to Formula (I) embraces compound species wherein the A ring moiety can be any of the optionally substituted nitrogen containing heteroaryls or heterocycles selected from azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, tetrahydropyridazinyl, 1,4- azaphosphinane 4-oxide, pyrazolyl, isoindolinyl, dihydropyrrolo[3,4-c]pyridinyl, decahydroquinolinyl, tetrahydropyridinyl, tetrahydroisoquinolinyl, tetrahydronaphthyridinyl, hexahydrocyclopenta[c]pyrrolyl, hexahydrofuro[3,4-c] pyrrolyl, tetrahydropyrazolo[4,3-c]pyridinyl, tetrahydroisoxazolo[4,5-c]pyridinyl,tetrahydro[1,2,4]triazolo[4,3-a]pyrazinyl, octahydroisoindolyl, octahydropyrrolo[3,4- b]pyridinyl, octahydrocyclopenta[c]pyrrolyl, octahydropyrrolo[3,4-c]pyrrolyl, azaspiro[3.3]heptanyl, diazaspiro[3.3]heptanyl, oxaazaspiro[3.3]heptanyl, diazaspiro[3.4]octanyl, oxaazaspiro[3.4]octanyl, azaspiro[3.5]nonanyl, oxaazaspiro[3.5]nonanyl, diazaspiro[3.5]nonanyl, diazaspiro[4.4]nonanyl, azaspiro[4.5]decanyl, diazaspiro[4.5]decanyl, oxaazaspiro[4.5]decanyl, diazaspiro[4.5]decanonyl, oxadiazaspiro[4.5]decanyl, spiro[indoline-3,4'-piperidinyl], 2H-spiro[benzofuran-3,4'-piperidinyl], 3H- spiro[isobenzofuran-1,4'-piperidinyl], 2,3-dihydrospiro[indene-1,4'-piperidinyl],azabicyclo[3.1.0]hexanyl, azabicyclo[3.1.1]heptanyl, oxaazabicyclo[3.1.1]heptanyl,azabicyclo [3.2.1] octanyl, diazabicyclo [3.2.1] octanyl, or oxaazabicyclo [3.2.1] octanyl.
12. The instant compounds are alleged by the Specification to be Helios protein inhibitors, which can control Treg differentiation and may be useful as therapeutics for the treatment of diseases including cancer and viral infections (page 5, sixth paragraph). Applicant demonstrates the in vitro inhibitory activity of compounds 1-87 on Helios Jurkat cells in Table A (pages 179-181) and the degradation concentration of compounds 88-283 against Treg Helios cells in Table B (pages 182-187).
13. Method of making: It is evident that the genus of compounds embraced by the claims has substantial variance, for example, the ring comprising “A” encompasses a broad Markush group of nitrogen-containing unsubstituted or substituted heterocycle or heteroaryl moieties listed above in paragraph 13, and “R1” embraces various heteroaryl moieties, wherein said heterocycle or heteroaryl groups do not all belong to the same classification, such that the compounds prepared from each individual “A” moiety require different search strategy and consideration. And, the full scope of compounds of Formula (I) embraces hundreds of thousands of compound species, and potentially millions of compound species, i.e., all possible combinations of variables of Formula (I) and their alternatives, i.e., R1, R2, R3, R4, A, Z, Rx, Ry, m, n, p and q. Yet, the instant Specification discloses the preparation of just 289 compound species according to instant Formula (I) (and as recited by claim 12), in the syntheses disclosed in pages 74-178 and Tables 1-27.
14. While the MPEP does not define what constitutes a sufficient number of representative species, the courts have indicated what does not constitute a representative number of species to adequately describe a broad generic claim. For example, in In re Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d 1008 (Fed. Cir. 1989). In the instant case, it is similarly determined that the disclosure of the preparation of 289 compounds does not adequately describe a genus embracing hundreds of thousands, if not millions, of possible compounds embraced by the full scope of Formula (I). That is, the Specification does not disclose a sufficient variety of species to reflect the breadth of the possible compound selections recited in the claims.
15. The level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology. Ariad, 598 F.3d at 1351, 94 USPQ2d at 1172; Capon v. Eshhar, 418 F.3d 1349, 1357-58, 76 USPQ2d 1078, 1083-84 (Fed. Cir. 2005). The fields of biology and chemistry are considered “unpredictable” because the complexity and unpredictability of chemical and biological interactions can make it difficult to understand the exact properties of an invention. The pharmaceutical industry is the prototypical example of a highly unpredictable field. Pfizer v. Teva Pharm., 482 F.Supp.2d 390, 413 (D.N.J. 2007); 2 Chisum on Patents § 5.04.
16. Applicants have failed to provide guidance or data or evidence as to how the skilled artisan would be able to extrapolate from the disclosure to use the claimed invention. “A description of what a material does, rather than of what it is, usually does not suffice." Rochester, 358 F 3d at 923; Eli Lilly, 119 at 1568. Instead, the “disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described.” Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear the "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116).
17. The description requirement of the patent statue 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.").
18. Accordingly, it is deemed that the specification fails to provide adequate written description for the full scope of the genus of compounds of Formula (I) as recited in the claims 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.
As such, claims 1-11 and 13 are rejected.
Response to Arguments
19. Applicant traverses the written description rejection, and argues that regarding genus claims in chemical cases, the Federal Circuit has recognized that a specification can demonstrate possession of a genus through a variety of means, including: (1) a representative number of species falling within the scope of the genus, (2) structural features common to the members of the genus, and (3) working examples that illustrate the breadth of the claimed genus, MPEP 2163, citing Ariad, 598 F.3d at 1351.
Applicant argues that the USPTO's own written description guidelines confirm that a specification need not contain a working example for every species in a claimed genus, provided that the disclosure as a whole demonstrates possession of the genus. MPEP § 2163. Furthermore, the mere fact that chemistry is in an "unpredictable" field does not automatically render a genus claim deficient for written description purposes; rather, unpredictability is but one factor to be weighed against the totality of disclosure. Capon, 418 F.3d at 1358.
Applicant alleges that in the instant application, the claims are directed to structurally defined compounds of Formula (I), not to an open-ended functional genus. Ring A is limited to an enumerated set of nitrogen-containing heterocyclic rings, and the specification discloses numerous species of Formula (I), including examples covering the Ring A groups recited in claim 1. Applicant alleges that the disclosure provides representative species and common structural features sufficient to demonstrate possession of the claimed genus.
Applicant contends that the office relies in part on the alleged unpredictability of chemistry and biology, however, unpredictability is only one factor in the written description analysis and does not, by itself, establish lack of possession. Applicant alleges that the instant specification provides structural definitions and working examples supporting the claimed Ring A groups. Viewed as a whole, the disclosure reasonably conveys to those skilled in the art that the inventors possessed the claimed compounds as of the filing date.
Applicant contends that this is not a case in which the invention is defined solely by function or by a method of making, i.e., the claims recite specific structural features of compounds of Formula (I), and the specification provides examples of those features. While the specification describes the utility of the compounds, the claims do not rely solely on the function or method of making the invention.
20. Applicant's arguments have been fully considered but they are not persuasive. Regarding Applicant’s allegation that the instant specification discloses numerous species of Formula (I) including examples covering the Ring A groups recited in claim 1, providing representative species and common structural features sufficient to demonstrate possession of the claimed genus, the specification provides at least one example of a compound according to Formula (I) comprising each of the recited Ring A groups. However, the specification has not demonstrated sufficient support for all possible alternatives prepared from the various combinations of Ring A, R1, R2, R3, R4, A, Z, Rx, Ry, m, n, p and q.
21. Ring A encompasses a broad Markush group of unrelated nitrogen-containing unsubstituted or substituted heterocycle or heteroaryl moieties, and “R1” embraces various heteroaryl moieties, wherein said heterocycle or heteroaryl groups do not all belong to the same classification, such that the compounds prepared from each individual “A” moiety and R1 moiety require different search strategy and consideration. And, the full scope of compounds of Formula (I) embraces hundreds of thousands of compound species, and potentially millions of compound species, i.e., all possible combinations of variables of Formula (I) and their alternatives, i.e., R1, R2, R3, R4, A, Z, Rx, Ry, m, n, p and q. Yet, the instant Specification discloses the preparation of just 289 compound species according to instant Formula (I) (and as recited by objected claim 12), in the syntheses disclosed in pages 74-178 and Tables 1-27. As such, the claim is extremely broad with respect to the disclosure.
22. Regarding Applicant’s allegation that unpredictability is only one factor in the written description analysis and does not, by itself, establish lack of possession, in the instant case, this unpredictability is exacerbated by the broadness of Formula (I) with respect to the disclosure since Formula (I) encompasses hundreds of thousands, and potentially millions of compound species, whereas the instant Specification discloses less than 300 such compound species.
As such, the disclosure does not demonstrate sufficient support for the full scope of compounds and all possible alternatives embraced by instant Formula (I).
Previous Double Patenting Rejections
23. 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).
24. 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).
25. 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.
26. 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.
27. Claims 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 12 of U.S. Patent No. 12,570,671 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because Applicant’s instant claim 1 is drawn to a compound of Formula (I):
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or a salt thereof, and its pharmaceutical composition (Claim 13). Claims 2 and 3 limit “Z.” Claims 4 limit R1. Claim 5 limits Ring A to azetidinyl, pyrrolidinyl, or piperidinyl that are substituted by at least one R1. Claim 6 limits Ring A to azetidinyl. Claim 7 limits Ring A to pyrrolyl. Claim 8 limits Ring A to piperidinyl. Claims 9-11 limit R1. Claim 12 limits to species according to Formula (I).
26. U.S. Pat. No. 12,570,671 B2 recites the following genus of compounds:
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, that are Helios protein inhibitors, wherein “Ring A” is pyridine and “R1” is piperidinyl or pyrrolidinyl that is substituted by at least one “R1b,” which embraces the same species of Applicant’s instant claims in which Z is CR6R6 and R6 is hydrogen, and ring A is piperidinyl or pyrrolidinyl substituted by at least one R1.
As such, it would have been obvious to one of skill in the art to prepare the same species of compounds that are embraced by the limited genus of Formula (I) recited by U.S. Pat. No. 12,570,671 B2, with a reasonable expectation of success.
27. Claims 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 12 of U.S. Patent No. 11,548,870 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because Applicant’s instant claim 1 is drawn to a compound of Formula (I):
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or a salt thereof, and its pharmaceutical composition (Claim 13). Claims 2 and 3 limit “Z.” Claims 4 limit R1. Claim 5 limits Ring A to azetidinyl, pyrrolidinyl, or piperidinyl that are substituted by at least one R1. Claim 6 limits Ring A to azetidinyl. Claim 7 limits Ring A to pyrrolyl. Claim 8 limits Ring A to piperidinyl. Claims 9-11 limit R1. Claim 12 limits to species according to Formula (I).
26. U.S. Pat. No. 11,548,870 B2 recites the following genus of compounds:
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that are Helios protein inhibitors, wherein “Ring A” is pyridine and “R1” is –(CRzRz)-NR1aR1b wherein R1a and R1b form a cyclic group selected from:
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,
which embraces the same species of Applicant’s instant claims in which Z is CR6R6, R6 is hydrogen, and ring A is azepanyl, azetidinyl, octahydropyrrolo[3,4-c]pyrrolyl, tetrahydroisoquinolinyl, piperidinyl or pyrrolidinyl, wherein azetidinyl, piperidinyl or pyrrolidinyl are substituted by at least one R1d.
As such, it would have been obvious to one of skill in the art to prepare the same species of compounds that are embraced by the limited genus of Formula (I) recited by U.S. Pat. No. 12,570,671 B2, with a reasonable expectation of success.
27. Claims 1 and 13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of copending Application No. 19/488,904 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other. Applicant’s instant claims are described in detail, above.
28. U.S. Application No. 19/488,904 recites the following compound:
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, which is identical to a compound species of Applicant’s instant Formula (I) wherein Ring A is azaspiro[3.5]nonanyl, R3 is -NH2, and Z is CR6R6 wherein R6 is hydrogen.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicants requests that the nonstatutory obviousness-type double patenting rejections be held in abeyance until the allowability of the remaining claims is determined.
Accordingly, the previous double patenting rejections are maintained.
Claim Objections
29. Claim 12 is objected to as being dependent upon a base claim, i.e., claim 1, which is rejected under 35 USC § 112(a).
Conclusion
30. Claims 1-13 and 16-19 are present in the application. Claims 16-19 are currently withdrawn as directed to nonelected subject matter. Claims 1- 13 are rejected. Claim 12 is objected to. No claim is presently allowable.
31. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
32. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L COPPINS whose telephone number is (571)272-0680. The examiner can normally be reached Monday-Friday 8:30AM-5PM EST.
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, Amy L Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
