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 without traverse of:
(i-a) a Syk Inhibitor;
(i-b) Bosutinib (SKI-606) and an analog thereof; and
(ii-c) both prophylaxis and treatment of ALS,
in the reply filed on 7/9/2018 remains acknowledged. The Examiner notes a prior cancelation of the “prophylaxis” embodiment. No claim recites a Syk Inhibitor; no claim recites an analog of Bosutinib. Thus, subject matter under examination was changed to the (ii-b) treatment of ALS (in place of elected (ii-c)), remaining in claim 16. The active agent is (i-b) bosutinib (SKI-606), currently recited in independent claim 16. The election under (i-a) a Syk inhibitor is no longer relevant to the claims
Claims 39, 41 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/9/2018.
The claims drawn to the elected species were previously indicated not to be allowable (see rejections presented below). Therefore, the election was given effect and examination has been limited to the Markush-type claim and claims to the elected species (see MPEP 803.02).
Prior submitted claims 43-48 were found to be directed to an invention that is independent or distinct from the invention originally claimed.
Claims 44-48 remain withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
Examiner acknowledges the claim amendment filed 8/20/2025, in which independent claim 16 has been amended as follows:
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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 16, 40, 42 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.
Amended claim 16 introduces new matter. Review of the specification failed to identify the recited comparison of claim 16 as currently amended, “orally administering an effective amount of bosutinib (SKI-66) to the subject, wherein the subject is one in whom no therapeutic effect is observed when administered an inhibitor selected from tivozanib, crizotinib, pazopanib, and axitinib…” This requires both a positive effect, a treatment, when administering an effective amount of bosutinib and a negative effect, i.e., no therapeutic effect when the subject is administered an inhibitor selected from tivozanib, crizotinib, pazopanib, and axitinib (i.e., at least one of these 4 compounds are administered to the patient. The claim also requires the subject to have one of the 3 types of ALS named in the claim. The claim implies each type of recited ALS has the comparison outcome for bosutinib and each of the second compounds. The negative outcome for each of the second compounds in each of the ALS type subjects was not identified in the specification. The recited comparison of the claims was not identified in the specification, and thus, introduces new matter.
Claim Rejections - 35 USC § 102/103
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 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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
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 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.
Claim(s) 16, 40, 42 is/are rejected under 35 U.S.C. 102(a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Rubin (US 2016/0082015 A1; 2016; filed 2014 Apr; priority 2013; cited in a prior Office action).
Regarding the amended language of claim 16, Examiner relies on instant Tables 5 and 6 to document the properties of the claims are inherent to certain embodiments of Rubin.
Rubin teaches methods for treatment of neurodegenerative disorders such as Amyotrophic lateral sclerosis (ALS) are described herein (abstract). A method of treating ALS in a subject in need thereof, comprising administering an effective amount of an agent that inhibits HGK (HPK/GC kinase-like kinase, [0006], [0072], also known as mitogen-activated protein kinase kinase kinase kinase 4, MAP4K4, [0073]) to the subject [0007], claim 4. It should be appreciated that the HGK inhibitor can be any of the inhibitors described herein [0190]. Table 1 includes exemplary agents that inhibit HGK [0081]. Among the compounds is the currently recited bosutinib (Table 1, [0081]).
Regarding a prior amendment to independent claim 16, in some embodiments, the motor neuron comprises a mutation in a gene encoding superoxide dismutase 1 (SOD1) [0004], [0022], claim 121. Most cases of ALS occur sporadically; and there is a familial form which often results from mutation of the superoxide dismutase gene or SOD [0226]. A very recent identification of a hexanucleotide repeat expansion within the C0orf72 gene points to it as the most frequent pathogenic cause of ALS identified thus far, accounting overall for about 6% of sporadic ALS cases and about 36-40% of familial ALS cases [0004]. Thus, in treating ALS [0009] with bosutinib (Table 1), treating each patient subpopulation, having a SOD1 mutation, sporadic ALS and a mutation of C9orf72 gene, is construed as including the step of selecting a subject suffering from one of these types of ALS, claim 16, step (i). The administering step is taught, step (ii). Thus, the claimed methods, involving each alternative patient subpopulation, are each separately anticipated.
Regarding a prior amendment, the subject “not suffering from ALS having mutation in TDP-43 gene” (amended claim 16, lines 5-6), mutations in TARDBP, the gene encoding TCP-43, were identified in ~4% of familial ALS cases is specifically recognized [0004]; thus all other ~96% of familial ALS cases are construed as subjects “not suffering from ALS having mutation in TDP-43 gene”. Other causes named at [0004] are construed as corresponding to an alternate cause from ALS having mutation in TDP-43 gene, as there is no indication of multiple causes of a mutation in TDP-43 gene + any alternate cause coexisting in the same subject; i.e., SOD1 gene mutations, sporadic ALS, & C9orf72 gene mutations each read on the instant claimed patient subpopulations of claim 16, 40 & 42.
Regarding the amended language of claim 16, when bosutinib is administered to a subject with (a) ALS having mutation in C9orf72 gene, Table 6 documents that cell survival rate improvement less than 20% occurs with tivozaniv and crizotinib. This is relied on as evidentiary that the stated comparison is satisfied for these two second compounds.
Regarding when bosutinib is administered to a subject with (b) sporadic ALS, instant Table 5 documents bosutinib has a significant difference in cell survival rate of sporadic ALS cells, but each of crizotinib, pazopanib and axitinib do not have a significant difference. This is relied on as evidentiary that the stated comparison of claim 16 is satisfied for the bosutinib comparison to each of crizotinib, pazopanib and axitinib.
Regarding orally administered, now required by independent claim 16, (1) Oral administration of the compounds and/or agents is taught by Rubin [0347]. Regarding the claimed oral dose range, [0359] indicates about 100 mg to 2000 mg of compound and/or agent is preferred for oral compositions. This range substantially overlaps with the amended claim 16 range at least 0.1 mg at most 1000 mg, construed as having sufficient specificity for anticipation of the oral dosing range. See MPEP 2131.03 (II):
In ClearValue, the claim at issue was directed to a process of clarifying water with alkalinity below 50 ppm, whereas the prior art taught that the same process works for systems with alkalinity of 150 ppm or less. In holding the claim anticipated, the court observed that "there is no allegation of criticality or any evidence demonstrating any difference across the range." Id. at 1345, 101 USPQ2d at 1777.
This appears to be comparable facts to the instant case, where there is substantial overlap of ranges between Rubin and the claim amendment. The overlap is broad, and there does not appear to be any criticality, or evidence of a difference across the range.
Regarding the amended claim range, even if the sufficient specificity were determined not to be taught in the prior art sufficient for anticipation, the overlap in ranges for oral dosing alternately renders the claims obvious.
See MPEP 2144.05 (I):
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.)
The instant facts embrace a broader overlap than Wertheim, clearly applying to render the claims prima facie obvious.
Claims 16, 40, 42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rubin (US 2016/0082015 A1; 2016; filed 2014 Apr; priority 2013; cited in a prior Office action) as applied to claims 16, 40, 42 above.
Teachings of Rubin are set forth above, which anticipate and alternately render obvious the instant claims.
The position has been adopted that ALS with a 9orf72 mutation and sporadic ALS subpopulations are each explicitly taught by Rubin; comparing the second compounds to bosutinb according to disclosed Tables 5 and 6 demonstrate the recited comparison of claim 16, as stated above.
The comparative language of claim 16 is relied on as inherent, based on evidence from the two tables. Even if the teachings were construed as insufficient to anticipate this language, the instant disclosed evidence alternately establishes this inherent property is obvious.
Examiner notes that the comparison of claim 16 is functional property of the subject, and does not actually require administration of the second compound, but may be satisfied by identifying this property from, say, a reported Table; i.e., the recited property of the subject (no therapeutic effect observed) is characteristic of the particular ALS type.
See MPEP 2112 III:
Where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103. "There is nothing inconsistent in concurrent rejections for obviousness under 35 U.S.C. 103 and for anticipation under 35 U.S.C. 102." In re Best, 562 F.2d 1252, 1255 n.4, 195 USPQ 430, 433 n.4 (CCPA 1977). This same rationale should also apply to product, apparatus, and process claims claimed in terms of function, property or characteristic. Therefore, a 35 U.S.C. 102 and 103 rejection is appropriate for these types of claims as well as for composition claims.
The instant process claims rely on a comparative characteristic of a second series of administration(s); the instant Tables document this occurs for two of the claims ALS types with either two or three of the second compounds, in specific ALS types, as documented above. Accordingly, the rejection is being made under both 35 USC 102 and 103, as authorized in this MPEP section.
Applicant argues that Rubin does not disclose or suggest subjects in whom no therapeutic effect is observed when administered an inhibitor selected from tivozanib, crizotinib, paxopanib, and axitinib, and Rubin does not even refer to administration of an inhibitor selected from tivozanib, crizotinib, pazopanib and axitinib to a subject.
This is not persuasive. As discussed in the rejection,
Regarding the amended language of claim 16, when bosutinib is administered to a subject with (a) ALS having mutation in C9orf72 gene, Table 6 documents that cell survival rate improvement less than 20% occurs with tivozanib and crizotinib. This is relied on as evidentiary that the stated comparison is satisfied for these two second compounds.
Regarding when bosutinib is administered to a subject with (b) sporadic ALS, instant Table 5 documents bosutinib has a significant difference in cell survival rate of sporadic ALS cells, but each of crizotinib, pazopanib and axitinib do not have a significant difference. This is relied on as evidentiary that the stated comparison of claim 16 is satisfied for the bosutinib comparison to each of crizotinib, pazopanib and axitinib.
Thus, the subject is a match for bosutinib administered to a patient having ALS having mutation in C9orf72 gene; and alternatively to a patient having sporadic ALS cells, as evidenced by the tovpzanib and crizotinib data of Table 6 and as evidenced by the cizotinib, pazopanib, and axitinib data of Table 5. In other words, the comparative subject effect of claim 16 is satisfied by the comparisons to bosutinib efficacy of Table 5 & 6 for specific embodiments outlined in the rejection basis. The administration of the second compounds of claim 16, lines 5-6 is not construed to be a required step, but this subject selection (specific types of ALS) are characteristic of bosutinib being administered to the named ALS patients taught by Rubin: having mutation in C9orf72 gene; and alternatively having sporadic ALS cells
It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph).
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 16, 40, 42 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 4 of copending Application No. 16/766675. (reference application), in view of Rubin (US 2016/0082015 A1; 2016; filed 2014 Apr; priority 2013; cited in a prior Office action). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims recite a method of treatment of ALS caused by one or two of 2 mutations or sporadic ALS, without having one specific mutation; the method requires selecting a subject having one of the named causes, and orally administering bosutinib, where the amount is broadly claimed. In contrast the copending claim 4, recites a method for treating ALS (no cause is claimed), comprising administering bosutinib. The copending claim also recites bosutinib is a specific Src/c-Abl inhibitor, which is inherent to this compound, recited in both claim sets. The current amendment recites a wherein clause, where a subject outcome is established by comparison to one of 4 second compounds found not to be effective; as discussed above, teachings of Rubin are set forth, and document the instant claimed ALS types are taught by Rubin, rendering obvious one of these ALS types in the copending claims. The inherence of the comparative language is also established for reasons above. Thus, the instant claims anticipate and render obvious the copending claim, rendering the claims obvious over each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant requests this provisional rejection be held in abeyance.
The Examiner notes that MPEP 804 (I) (B) (1) indicates:
A complete response to a nonstatutory double patenting rejection (also called an "obviousness-type" or ODP rejection) is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims or the filing of a terminal disclaimer in accordance with 37 CFR 1.321 in the pending application(s) with a reply to the Office action (see MPEP § 1490 for a discussion of terminal disclaimers). Such a response is required even when the nonstatutory double patenting rejection is provisional.
…
As filing a terminal disclaimer, or filing a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, is necessary for further consideration of the rejection of the claims, such a filing should not be held in abeyance. Only objections or requirements as to form not necessary for further consideration of the claims may be held in abeyance until allowable subject matter is indicated.
Neither arguments that the claims are patentably distinct over each other, nor the filing of a terminal disclaimer reply options have been pursued. Applicant is cautioned that additional requests to hold the provisional ODP rejection in abeyance are not considered a complete response.
Conclusion
No claim is allowed.
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 TIMOTHY P THOMAS whose telephone number is (571)272-8994. The examiner can normally be reached M-Th 6:30-5:00.
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, Ali Soroush can be reached at (571)272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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TIMOTHY P. THOMAS
Primary Examiner
Art Unit 1614
/TIMOTHY P THOMAS/ Primary Examiner, Art Unit 1614