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 .
Election/Restrictions
Applicant's election with traverse of Group I, claim 1, drawn to a compound of Formula I or an analog thereof, in the reply filed on August 20, 2026 is acknowledged. The traversal is not found persuasive because the inventions of Groups I and II are independent and distinct because the compound BCN057 of Group I can be used in different methods of treatment including chemotherapy, treating autoimmune diseases, and as an anti-inflammatory agent. The inventions of Group I (CPC C07D 471/04) and Group II (CPC A61K 31/4709) are also classified differently; therefore the different Groups require different search strategy, parameters and consideration.
The requirement is still deemed proper and is therefore made FINAL.
Claims 2-20 (Group II, drawn to methods) are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicant additionally elected the compound species BCND001:
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, which corresponds to a compound of Formula 1 wherein R2 = CH3, R3= OCH3, and R1 =
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, however it is noted that Applicant failed to define “X.” The elected compound species BCND001 also fails to include a substituent corresponding to “X” on the thiophene ring. In claim 1, “X” is limited to F, CF3, Cl, OH, or CH2OH; therefore the elected species is not consistent with a compound of Claim 1.
Claim 1 is under examination and is the subject of this office action.
Drawings
The drawings are objected to because of the following informalities:
In Figure 2B, the line plots of Vehicle, 1 hr and 12 hr are difficult to distinguish such that it is not clear what line corresponds to which duration of time. And, four lines appear on the graph yet only three are defined in the key, (i.e., Vehicle, 1 hr and 12 hr).
In Figure 2C, the three bars for each type of cell line are not defined.
In Figure 5A, the bars are difficult to differentiate, i.e., ND and 5FU+057 appear to be the same shade.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities: the chemical structures depicted at pages 37, 75-78, 81 and 82 are blurry such that some of heteroatoms and bonds are unclear and the –[CH2]n- moiety is difficult to read in each structure.
Appropriate correction is required.
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 1 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 1 is problematic in the following aspects:
(a) The definition of R1 is confusing, because in the first line of R1 (line 5 of the claim), the claim recites that R1 is “an alkyl, an alkyl amine, an ether, an aryl, an aryl halide,” and then beginning at line 6, the claim also recites “independently selected from the group consisting of…[language omitted]” such that it is not clear if the features recited in line 5 are exemplary or are required features of the “group consisting of” recited in the definition of R1, beginning at line 6. Clarification is requested.
(b) A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 recites the broad recitation “R1=alkyl” in line 5, and the claim also recites “optionally substituted C1-C20 alkyl” in line 8 which is confusing because it is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
(c) Claim 1 recites the limitation “R1= an aryl” in line 5, and the claim also recites “optionally substituted aryl” in lines 10-11, and “optionally substituted phenyl” in line 12, which is confusing because “optionally substituted aryl” is repetitive and redundant, and “optionally substituted phenyl” is the narrower statement of the limitation “optionally substituted aryl”. The claim(s) are considered indefinite because there is a question or doubt as to whether the features introduced by such narrower language are (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) required features of the claims.
(d) Claim 1 recites the limitation “R1=an aryl halide” in line 5, and the claim also recites “optionally substituted aryl halide” in line 11 which is confusing because it is repetitive and redundant, and it is not clear if the feature “optionally substituted aryl halide” is (a) merely exemplary of aryl halide, and therefore not required, or (b) a required feature of the claims.
(e) In claim 1, in the the Markush group of “functional group[s]” listed at the bottom of page 1 and on page 2, it is not clear how the functional group attaches to R1, i.e., the claim does not indicate a point of attachment on each group to the R1 site.
Looking to the Specification (structure of BCN057 in paragraph [00130] and Table 2 at pages 88-94), the point of attachment for said functional groups is the -NH2- group wherein a H is cleaved:
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. Therefore, in view of a broadest reasonable interpretation, the point of attachment of said functional groups is at the amino group.
(f) The “functional group” chemical structures (two structures at the bottom of page 1 and all twelve structures on page 2) are blurry, some of the bonds are unclear, and the –[CH2]n- moiety is difficult to read in each structure, such that the metes and bounds of the “functional group(s)” of Formula 1 cannot be ascertained.
Claim Rejections - 35 USC § 112(a)
15. 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.
16. Claim 1 is 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 full scope of compounds and alternatives according to the genus of Formula 1. 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.
17. In particular, support cannot be found for the full scope of dihydroquinoline compounds of Formula 1 or an analog thereof, as instantly recited by claim 1.
18. 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. The problem is especially acute with genus claims that uses open-ended language such as “an analog thereof.” In such a case, the claim simply recites the generic “analog,” and may do so without describing species that achieve that result. But the specification must demonstrate that the Applicant has made a generic invention that achieves the claimed result and do so by showing that the Applicant has invented sufficient alternative species to support the claim to the generically-defined genus.
19. 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.
20. 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.
21. Partial structure; Physical and/or chemical properties; and Functional characteristics: The claims are drawn to a compound according to the extremely broad genus of Formula 1:
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, or an analog thereof. The claimed genus of Formula 1 is extremely broad, embracing hundreds of millions of potential compound species, if not billions of compound species and analogs thereof, which bear little structural overlap with one another, e.g., presently the genus of compounds of Formula 1 encompasses compound species wherein R1 is any aryl group, any heteroaryl group, any heterocycloalkyl group, or the 5- and 6- membered heteroaryl groups embraced by the “functional group,” or any analog thereof, without limit. “Analog thereof,” without being defined or limited by the disclosure, embraces any compound differing in one or more atoms, functional groups, and/or isomerism from that of Formula 1, embracing an extremely vast scope of derivatives and alternatives. Thus, it is evident that the genus of compounds and analogs encompassed by claim 1 has substantial variance.
Yet, the instant Specification discloses the preparation of only one compound species, BCN057 (page) and discloses about a dozen analogs in Table 2 at pages 88-94.
22. The instant dihydroquinoline compounds are alleged by the Specification to have PD-1 inhibitory activity, and GSK3b inhibitory activity, which are potentially useful in modulating chemosensitivity of pancreatic cancer cells, for example (Specification at pages 4-5). Applicant demonstrates a few in vitro assays demonstrating the activity of just one compound, BCN057: a Panc-1 cell viability assay with increasing doses of BCN057 in Example 1; inhibitory activity of BCN057 against GSK33 signaling in Panc-1 cells in Example 2; the ability of BCN057 to enhance activity of cytotoxic chemo-therapeutic agents in Example 3 (Specification at pages 47-53 and Figures 1-9, 11 and 12).
23. Method of making: It is evident that the genus of compounds and analogs thereof embraced by Formula 1 of the claims has substantial variance, as discussed in paragraph “21” above, embracing hundreds of millions, if not billions of compound species, without any limit whatsoever. Yet, the instant Specification discloses the preparation of one compound, BCN057, and about a dozen analogs according to instant Formula 1 in Table 2 at pages 88-94, wherein R1 is limited to a the subgenus of “functional groups” recited in clam 1.
24. 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 a few dozen compound does not adequately describe a genus embracing billions of possible compounds. 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.
25. 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.
26. 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).
27. 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.").
28. Accordingly, it is deemed that the specification fails to provide adequate written description for the full scope of compounds embraced by Formula 1 and their analogs, as recited by the claims, and does not reasonably convey to one skilled in the relevant art that the applicant, at the time the application was filed, had possession of the entire scope of the claimed invention.
As such, claim 1 is rejected.
Claim Rejections - 35 USC § 102
29. 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.
30. Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by STN Registry No. 581069-99-0 (entered STN and published September 8, 2003), i.e., the compound 3-[3-[(1,1-dimethyl-propyl)amino]-imidazo[1,2-a]pyridin-2-yl]-7-methoxy-2(1H)-Quinolinone:
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The compound of Registry No. 581069-99-0 is the same as a compound of Applicant’s Formula 1 wherein R1 is alkylamine; R2 is H; and R3 is -OCH3.
31. Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by STN Registry No. 581069-98-9 (entered STN and published September 8, 2003), i.e., the compound 3-[3-[(1,1-dimethyl-ethyl)amino]-imidazo[1,2-a]pyridin-2-yl]-7-methoxy-2(1H)-Quinolinone:
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The compound of Registry No. 581069-98-9 is the same as a compound of Applicant’s Formula 1 wherein R1 is alkylamine; R2 is H; and R3 is -OCH3.
32. Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by STN Registry No. 581070-02-2 (entered STN and published September 8, 2003), i.e., the compound 3-[3-[(1,1-dimethyl-ethyl)amino]-8-methylimidazo[1,2-a]pyridin-2-yl]-7-methoxy-2(1H)-Quinolinone:
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The compound of Registry No. 581070-02-2 is the same as a compound of Applicant’s Formula 1 wherein R1 is alkylamine; R2 is -CH3; and R3 is -OCH3.
Double Patenting
33. 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).
34. 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).
35. 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.
36. 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.
37. Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11,358,964 B2.
38. Although the claims at issue are not identical, they are not patentably distinct from each other because instant claim 1 recites a compound of Formula 1:
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(wherein n is 1 and X is F),
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(wherein n is 2 and Z is -CH3).
39. The claims of U.S. Pat. No. 11,358,964 B2 recite the following:
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Claims 3-8 are drawn to claim 2 and further limit the disease, disorder or condition to be treated.
40. As such, U.S. Pat. No. 11,358,964 B2 recites the same compound species in Claim 1 that are recited by Applicant, wherein R1 is
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(wherein n is 1 and X is F), or
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(wherein n is 2 and Z is -CH3), and wherein R2 is H or -CH3; R3 and is -O-CH3.
U.S. Pat. No. 11,358,964 B2 recites the same compound species in Claim 2 that are instantly claimed by Applicant, wherein R1 is alkyl, alkyl amine, or ether; R2 is H or -CH3; and R3 is H or -OH.
As such, instant claim 1 is prima facie obvious over the claims of 18/595,355.
Conclusion
41. Claims 1-20 are present in the application. Claims 2-20 are withdrawn from consideration as directed to a non-elected invention. Claim 1 is rejected. No claim is presently allowed.
42. 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
