Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Applicant’s election without traverse of Group II, claims 15-23, and species: combination (b) of claim 15, in the reply filed on December 2, 2025 is acknowledged.
It is noted that the species election for the PAF-receptor antagonist is not applicable for the combination (b) of claim 15. However, in view of references, combination (d) of claim 15 is included in the examination. Accordingly, claims 18-20 are also included in the examination.
Claims 1-31 are pending.
Claims 1-14, and 24-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions or species, there being no allowable generic or linking claim.
Claims 15-23 are pending and under consideration.
It is noted that prior art does not teach an anti-cancer combination of ELV-N32 or ELV-N34 plus anti-VEGF antibody; ELV-N32 or ELV-N34 plus Suramab. However, the instant claims are not limited these combinations. Accordingly, all pending claims are rejected (see 112(a) and 103 rejections below).
Priority
It is acknowledged that this application is a 371 of International Patent Appl. No. PCT/US2021/049297, filed September 7, 2021, which claims the benefit of priority to U.S. Provisional Patent Appl. No. 63/074,968, filed September 4, 2020. The priority date has been established as: September 4, 2020.
Information Disclosure Statement
The Information Disclosure Statements filed on 09/11/2023, 08/16/2024, 08/16/2024, 01/09/2025 and 12/02/2025 have been considered and entered by examiner.
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 15-23 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.
Claim 15 is drawn to an anti-cancer composition, comprises: a) an elovanoid and a PAF-receptor antagonist; b) an elovanoid and an anti-VEGF antibody; c) an elovanoid and Suramab; d) a PAF-receptor antagonist and an anti-VEGF antibody; or e) a PAF-receptor antagonist and a Suramab. Thus, the claim encompasses a broad genus of elovanoids and a broad genus of PAF-receptor antagonists. Based on paragraph [0066] of the instant publication US 2023/0330094 A1, elovanoid would encompass all possible very-long-chain polyunsaturated fatty acid (VLC-PUFA) hydroxylated derivatives. These derivatives could have different length of carbon chain, different positions of double bonds, different levels of hydroxylation, different modifications to the carbon chain. In addition, the instant specification does not give a clear definition of “PAF-receptor antagonist”. Thus, given Broadest Reasonable Interpretation” (BRI), “PAF-receptor antagonist” would encompass a broad genus compounds that inhibit or interfere with the function of PAF-receptor. The specification does not limit the structure of PAF-receptor antagonists, thus, given BRI, the antagonists could be small molecule, peptide, antibody, oligonucleotide, genome editing system (e.g. CRISPR/Cas). These compounds vary significantly, have different structures and physical/chemical properties, and function through different mechanisms. Given the complexity of elovanoids and PAF-receptor antagonists, claim 15 encompasses an even bigger number of combinations of an elovanoid and a PAF-receptor antagonist.
The specification shows anti-cacner activity of only two elovanoids: ELV-N32 and ELV-N34, which are dihydroxylated derivatives of 32:6n3 and 34:6n3 (as evidenced by claim 17); only one PAF-receptor antagonist: LAU-0901; and anti-VEGF antibody in combination settings, see (Examples 2, 3 and 5). No other types of elovanoids or PAF-receptor antagonists have required activities/functions, such as anti-cancer activity in the claimed combinations. Thus, the specification lacks written description support for the claimed elovanoids and PAF-receptor antagonists used in the claimed combinations.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. (See Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001, especially page 1106 3rd column). A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. MPEP 2163 II.A.3a.ii.
Regarding elovanoids encompassed by the claims, as shown by Fig. 2 of Nwagbo (Nwagbo et al., Nutrients, 2023, 15, 3096, Publication Date: 07/10/2023), there are a large number of VLC-PUFAs with different chain length and structures. For example, some VLC-PUFAs can have as many as 13 double bonds (paragraph 1 of Introduction). Jun (Jun et al., Scientific Reports, 7: 5279, Publication Date: 07/13/2017) teaches VLC-PUFAs can exert various functions, but the molecular mechanisms by which VLC-PUFAs exert these functions remain unknown (page 2, para. 3). The data on elovanoids (derivatives of VLC-PUFAs) are mainly focused on ELV-N32 and ELV-N34 (see the whole document of Jun and the instant specification). However, given that the structures of elovanoids can vary significantly, including different length of carbon chain, different positions of double bonds, different levels of hydroxylation, different modifications to the carbon chain, ELV-N32 and ELV-N34 would not teach other elovanoids which have anti-cancer activity and can be used in combination with a PAF-receptor antagonist (such as LAU-0901) or an anti-VEGF antibody.
Regarding PAF-receptor antagonists, Hyland (Hyland et al., ChemMedChem 2018, 13, 1873-1884, Publication Date: 08/16/2018) teaches that a wide variety of molecules exhibit PAF receptor antagonistic activity (§ PAFr Antagonists). Although PAF/PAF-receptor are involved in many conditions, including cancers, lung diseases and neurodegeneration, specific therapeutic application of PAF-receptor antagonists are somewhat limited (page 1881, col. 2, para. 4). Many PAF-receptor antagonists show good potency and selectivity but suffer from issues of toxicity and bioavailability (the bridging paragraph of pages 1881-1882). Natural products that exhibit PAF-receptor antagonism are often not selective and arguably feature limited therapeutic potential (the bridging paragraph of pages 1881-1882). In view of above, the specification teaches only one compound of Formula (I): LAU-0901, which has anti-cancer activity and can be used with other compounds such as ELV-N32, ELV-N34 or anti-VEGF antibody. However, LAU-0901 would not teach other PAF-receptor antagonists encompassed by the claim, which have anti-cancer activity and can be used in combination with other compounds as claimed.
In addition, the instant specification has not provided a sufficient description about the correlation between the recited functions and the structure of the elovanoid or the PAF-receptor antagonist. Based on the specification and prior art, one of ordinary skilled in the art would not be able to “visualize or recognize” other members of the genus, excepted the ones described in the specification with the claimed functions, such as anti-cancer activity.
The instant specification fails to describe structural features common to the members of the genus, which features constitute a substantial portion of the genus because the instant specification discloses only a few elovanoids: ELV-N32 and ELV-E34, and only one PAF-receptor antagonist: LAU-0901, with claimed properties and functions. A definition by function does not suffice to define the genus because it is only an indication of what the elovanoids or PAF-receptor antagonists do, rather than what they are.
Claims 16 and 17 recite specific elovanoids, but the claims still encompass a broad genus of PAF-receptor antagonists.
Claims 18-20 recite specific PAF-receptor antagonists, but the claims still encompass a broad genus of elovanoids.
Taken together, the instant specification has not provided a sufficient description showing possession of the necessary functional characteristics coupled with a known or disclosed correlation between functions and the structure by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus of elovanoids, and/or the genus of PAF-receptor antagonists and combinations broadly encompassed by the rejected claims.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 15-23 are rejected under 35 U.S.C. 103 as being unpatentable over Bazan (Bazan et al., WO 2016/144995, Publication Date: 09/15/2016, of record) in view of Garcia (Garcia et al., CANCER TREATMENT REVIEWS, ELSEVIER, AMSTERDAM, NL, vol. 86, Publication Date: 03/26/2020, cited in IDS of 08/16/2024, of record).
Bazan teaches compound of Formula (I), such as LAU-09015, LAU-0901 (the elected species) (claims 1, 2, 8 and 12).
Bazan teaches a method of treating a brain tumor with a PAF-receptor antagonist of formula (I), such as LAU-0901, LAU-09015 (claims 7 and 8).
Bazan teaches that the brain tumor can be a glioblastoma (claim 9), in particular GBM (Examples 6-9).
Taken together, Bazan teaches an anti-cancer composition comprising a PAF-receptor antagonist of Formula (I), such as LAU-0901, or LAU-09015. It is noted that LAU-0901, or LAU-09015 reads on the instant claims 18-20. However, Bazan does not teach combination with other anti-tumor agents, such as anti-VEGF antibody.
Garcia teaches that bevacizumab is the standard treatment for GBM (page 10, col. 2), bevacizumab is an anti-VEGF antibody as evidenced by the instant claim 14.
Garcia also teaches that ongoing research into combining bevacizumab with other treatments (Table 4) to enhance its efficacy (page 15, col. 1, para. 4).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to modify the method of treating a GBM with a PAF-receptor antagonist of formula (I), such as LAU-0901, LAU09015 as taught by Bazan and to combine LAU-0901 and bevacizumab, because Garcia teaches that bevacizumab is a well-known and standard compound for treating GBM. One of ordinary skill would have been motivated and have expected that combination with bevacizumab would enhance the efficacy of the treatment by combining two mode of actions. Because both components are well known in the art, one of ordinary skill would have been motivated and have reasonable expectation of success to make an anti-cancer composition comprising both components for a simpler application.
Claim 16 is a limitation of the alternative elovanoid composition of claim 15, but it does not exclude the other alternative compositions such as option (d) of claim 15 from which it depends. Similarly, claim 17 does not exclude the other alternative compositions of claim 15 from which it depends.
Regarding claims 22 and 23, Bazan teaches pharmaceutical composition comprising a PAF-receptor antagonist and a pharmaceutically acceptable carrier and excipient, making the composition suitable for therapeutic use in vivo (page 13, para 3; the bridging paragraph of pages 15-16).
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 15-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 12,070,463 B2 (hereinafter Pat. 463) in view of Bazan (Bazan et al., WO 2016/144995, Publication Date: 09/15/2016, of record) and Garcia (Garcia et al., CANCER TREATMENT REVIEWS, ELSEVIER, AMSTERDAM, NL, vol. 86, Publication Date: 03/26/2020, cited in IDS of 08/16/2024).
Claim 1 of Pat. 463 teaches a method for treating a seizure caused by a brain tumor, the method comprising the steps: (a) selecting a subject in need of treatment, wherein the subject has been diagnosed with a brain tumor; and (b) administering a therapeutic composition comprising a therapeutically effective amount of a platelet-activating factor (PAF) receptor antagonist and a pharmaceutically acceptable carrier, wherein the PAF receptor antagonist is: LAU-09015, LAU-09018, LAU-09021, LAU-09023, LAU-09025. These PAF-receptor antagonists read on the antagonists of instant claims 18-20.
Claim 2 of Pat. 463 teaches that the brain tumor is selected from the group consisting of: a glioblastoma, an astrocytoma, an oligodendroglioma, an ependymal tumor, a neuronal tumor and a combination of glial tumors.
Taken together, the claims of Pat. 463 teach using PAF-receptor antagonists (such as LAU-09015) in a pharmaceutical composition to treat brain tumor related conditions and a therapeutic composition comprising a PAF-receptor antagonist and a pharmaceutically acceptable carrier. However, the claims of Pat. 463 do not teach the combinations such as PAF-receptor antagonist + an anti-VEGF antibody as instantly claimed.
Bazan and Garcia’s teachings are described above. In particular, Bazan teaches Bazan teaches compound of Formula (I), such as LAU-09015, LAU-0901, LAU-09018, LAU-09021, LAU-09023, and LAU09025 (claim 11), and treating tumor cancers with these antagonists (claim 7). Bazan teaches that the brain tumor can be a glioblastoma (claim 9), in particular GBM (Examples 6-9). Garcia teaches that bevacizumab is the standard treatment for GBM (page 10, col. 2), bevacizumab is an anti-VEGF antibody as evidenced by the instant claim 14.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to modify the method of treating a GBM with a PAF-receptor antagonist of formula (I), such as LAU-09015, LAU-0901, LAU-09018, LAU-09021, LAU-09023, or LAU09025 as taught by the claims of Pat. 463 and to combine these antagonists and bevacizumab as taught by Bazan and Garcia, because both these PAF-receptor antagonists and bevacizumab are well-known and standard compound for treating GBM, as evidenced by Bazan and Garcia. One of ordinary skill would have been motivated and have expected that combination would enhance the efficacy of the treatment by combining two modes of action for treating GBM. Because both components are well known in the art, one of ordinary skill would have been motivated and have reasonable expectation of success to make an anti-cancer composition comprising both components for a simpler application.
Claim 16 is a limitation of the alternative elovanoid composition of claim 15, but it does not exclude the other alternative compositions such as option (d) of claim 15 from which it depends. Similarly, claim 17 does not exclude the other alternative compositions of claim 15 from which it depends.
Conclusion
No claims are allowed.
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/CHENG LU/ Examiner, Art Unit 1642