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 .
Current Status of 18/291,703
This Office Action is responsive to the amended claims of 1/24/2024.
Claims 1-7, 9-20, and 23 are examined on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 1/24/2024, is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Priority
This Office Action is a national stage entry of PCT/EP2022/071167, which claims priority to US provisional applications 63/236,731 and 63/226,986.
The instant claims find support from the provisional applications. Therefore, the effective filing date is 07/29/2021.
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 3-7 and 10-18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 3-7 and 10-18 recite limitations that make these claims indefinite. For example, claim 2 recites “form A1”. It is unclear how one can have “form A1” (or another form) and it be characterized by variations in the XRPD. If the crystalline form does not have the peaks, space group, DSC, etc. it is unclear how the crystalline form is “form A1” (or the other forms with the respective data). These limitations that make these claims unclear and thus indefinite.
Claims 5 and 17 are indefinite. Claim 5 recites the limitation “comprises”; the form of claim 5 cannot “comprise” a space group. Comprise allows for additional elements, and it cannot contain modifications to the crystal lattice parameters and still be considered the space group or recited Form. Claim 17 has a similar limitation. These limitations that make these claims unclear and thus indefinite.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 3-5, 7, 16, and 17 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. The dependent claims recite inherent features of the crystal form and based on the disclosure, the compound would have all of those XRPD peaks. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 9 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 9 is broader than claim 1. Claim 1 is a solid form of the compound of formula 1. Claim 9 recites “at least one”, meaning it is now possible to have 2 or more of the solid forms as a “solid form”. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 1, 19, and 23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by KLEIN (Klein et al., “Structure-Based Optimization and Discovery of M3258, a Specific Inhibitor of the Immunoproteasome Subunit LMP7”, Journal of Medicinal Chemistry, July, 6, 2021), as provided in the IDS. Examiner also provides the supplemental data published on the same day.
Klein anticipates a crystalline structure of Compound 50 (also called M3258; Figure 3 B). This anticipates the solid form of compound 1 of claim 1.
Klein anticipates compound 50 (M3258) in a liquid composition (Table S4 on page 44 of the supplemental). This composition is known to contain a LMP7 inhibitor and is used in a preclinical in vivo model of multiple myeloma (MM) (conclusion; and “A lower daily oral dose of 0.3 mg/kg still resulted in significant tumor growth inhibition albeit less pronounced, while 0.1 mg/kg did not significantly affect tumor growth” on page 10237). Therefore, this is a pharmaceutical composition, which anticipates claim 19.
Klein describe the method for producing a medicament containing a solid form of compound 50 (M3258) (pages 2-4 of the supplemental, Section 2). This anticipates claim 23.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1, 19, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over KLEIN (Klein et al., “Structure-Based Optimization and Discovery of M3258, a Specific Inhibitor of the Immunoproteasome Subunit LMP7”, Journal of Medicinal Chemistry, July, 6, 2021, as provided in the IDS. Examiner also provides the supplemental data published on the same day), in view of HUA (Susan Hua, “Advances in Oral Drug Delivery for Regional Targeting in the Gastrointestinal Tract – Influence of Physiological, Pathophysiological and Pharmaceutical Factors”, Front. Pharmacol, April 27, 2020).
Klein teaches a crystalline structure of Compound 50 (also called M3258; Figure 3 B). This teaches the solid form of compound 1 of claim 1.
Klein teaches compound 50 (M3258) in a liquid composition (Table S4 on page 44 of the supplemental). This composition is known to contain a LMP7 inhibitor and is used in a preclinical in vivo model of multiple myeloma (MM) (conclusion; and “A lower daily oral dose of 0.3 mg/kg still resulted in significant tumor growth inhibition albeit less pronounced, while 0.1 mg/kg did not significantly affect tumor growth” on page 10237). Therefore, this is a pharmaceutical composition, which teaches claim 19.
HUA teaches that the oral route is the most preferred route for systemic and local drug delivery (abstract). HUA also teaches that the oral route is most preferred route by patients, due to its advantages, such as ease of use, non-invasiveness, and convenience for self-administration (abstract).
HUA teaches that Drug absorption in the GI tract is governed by many factors such as surface area for absorption, blood flow to the site of absorption, the physical state of the drug (such as a solution, suspension or solid dosage form), its water solubility, and the concentration of the drug at the site of absorption (introduction).
The artisan would have been motivated to administer Klein’s pharmaceutical composition to treat a LMP7-mediated disorder in a patient. The instant specification lists multiple myeloma as an LMP7 disease/condition (paragraph [00183]). The artisan would have expected the pharmaceutical composition to treat LMP7-mediated disorder (multiple myeloma) because the pharmaceutical composition is effective in the multiple myeloma animal model (Klein conclusion).
The artisan would further been motivated to formulate Klein’s solid compound 50 into an effective physical state (HUA introduction) in order to promote drug absorption in the GI tract. The artisan would expect to orally administer solids (tablets, etc) for treatment because of patient compliance and ease of use (HUA abstract). This teaches claim 20.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1, 19, and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 6 of copending US PG PUB 20230346815 (reference application) in view of HUA (Susan Hua, “Advances in Oral Drug Delivery for Regional Targeting in the Gastrointestinal Tract – Influence of Physiological, Pathophysiological and Pharmaceutical Factors”, Front. Pharmacol, April 27, 2020). Although the claims at issue are not identical, they are not patentably distinct from each other because the compound of ref claim 2 is the same compound of the instant claims. The reference claims teach the instant claims.
Reference claims 1 and 2 of US 20230346815 teach a compound
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Reference claim 6 teaches multiple myeloma. This helps teach instant claim 20.
The reference specification teaches pharmaceutical formulations/compositions like capsules or tablets (paragraph [0115]). This helps teach instant claim 19.
The reference claims do not specify a solid form.
HUA teaches that the oral route is the most preferred route for systemic and local drug delivery (abstract). HUA also teaches that the oral route is most preferred route by patients, due to its advantages, such as ease of use, non-invasiveness, and convenience for self-administration (abstract).
HUA teaches that Drug absorption in the GI tract is governed by many factors such as surface area for absorption, blood flow to the site of absorption, the physical state of the drug (such as a solution, suspension or solid dosage form), its water solubility, and the concentration of the drug at the site of absorption (introduction).
The artisan would have been motivated to administer the reference compound to treat a LMP7-mediated disorder (multiple myeloma) in a patient. The instant specification lists multiple myeloma as an LMP7 disease/condition (paragraph [00183]) and reference claim 6 teaches multiple myeloma as a an LMP7 disease/condition. The artisan would have expected the reference compound to treat LMP7-mediated disorder (multiple myeloma) because the reference claim 6 teaches it would be.
The artisan would further been motivated to formulate the reference compound (from ref claim 2) in a solid form (such as a tablet) in order to promote drug absorption in the GI tract (HUA abstract and introduction). The artisan would expect to orally administer solids (tablets, etc) for treatment because of patient compliance and ease of use (HUA abstract). The ref specification also teaches administering the ref compound in a tablet. This teaches claim 20.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Art of Record
Klein teaches an optional step, which was not done for Compound 14 or other compounds that are bortezomib derivatives, that Crystalline trimers comparable to those previously reported with bortezomib could be obtained by recrystallization (page 10234 left col).
Klein does not anticipate a trimeric crystalline anhydrous form of Compound 50. An artisan could be motivated to do this optional step given the explicit teaching. However, Klein is silent to an anhydrous form of compound 50. If Applicants amend the limitations of claim 2 into claim 1, Examiner would appreciate remarks for why it would not be obvious to make a trimeric crystalline anhydrous form of Compound 50.
US 2020/354382 A1, as provided in the IDS, discloses the compound of claim 1 (but not a trimeric anhydrous crystalline form or the XRPD peaks) (page 118).
A search for a trimeric crystalline anhydrous form of Compound 50 did not find any anticipatory prior art. The crystalline form of Compound 1 characterized by one or more peaks in its X-ray powder diffraction pattern from claims 3-7 has no prior art.
Conclusion
Claim 2 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
No claims are allowed as written.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GILLIAN A HUTTER whose telephone number is (571)272-6323. The examiner can normally be reached M-F 7:30-5.
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/G.A.H./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625