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
Election/Restrictions
Applicant’s election without traverse of Group I, abatacept, aldesleukin, subcutaneous administration, administration of abatacept every two weeks, administration of aldesleukin daily for 5 consecutive days, 125 mg abatacept, 106 IU aldesleukin, amyotrophic lateral sclerosis associated with stroke, and cognitive rehabilitation program in the reply filed on 5/21/2026 is acknowledged.
Claims 105, 112, 126, 141 and 152-153 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species/invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5/21/2026.
Status of the Claims
Claims 1-3, 6, 10-11, 16-18, 26, 31, 35, 42, 46, 50, 75, 93, 97, 103, 105-106, 112, 126, 141 and 152-159 are pending in this application.
Claims 105, 112, 126, 141 and 152-153 are withdrawn from consideration as being drawn to a non-elected species/invention.
Claims 1-3, 6, 10-11, 16-18, 26, 31, 35, 42, 46, 50, 75, 93, 97, 103, 106, and 154-159 are presently under consideration as being drawn to the elected species/invention.
Objections
Regarding the recitation of Tables 1A-1C, 2A-2C, and 3A-3C in claim 75, see MPEP 2173.05(s)- Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
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.
Claims 1-3, 6, 10-11, 16-18, 26, 31, 35, 42, 46, 50, 75, 93, 97, 103 and 154-159 are rejected under 35 U.S.C. 103 as being unpatentable over Perrin et al. (WO 2010/065819, previously cited) in view of Camu et al. (EBioMedicine 59 (2020) 102844, previously cited).
With respect to claims 1 and 103, Perrin et al. teach a method of treating a neurodegenerative or neuromuscular disorder comprising administering a CTLA4-lg fusion protein, wherein the disorder is Amyotrophic Lateral Sclerosis (claims 15-18 and 21).
Perrin et al. do not teach administering an IL-2 protein.
Camu et al. teach administering aldesleukin (i.e. an IL-2 protein) for the treatment of amyotrophic lateral sclerosis (i.e. a neurodegenerative disorder) (title; abstract; passim).
The MPEP 2144.06 states that "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from them having been individually taught in the prior art." In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169 USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-77, 126 USPQ 186, 188 (1960). As the court explained in Crockett, the idea of combining them flows logically from them having been individually taught in prior art.
Therefore, since the references teach that a CTLA4-lg fusion protein and an IL-2 protein are effective in treating neurodegenerative disorders, it would have been obvious to combine the two compounds with the expectation that such a combination would be effective in treating neurodegenerative disorders. Thus, combining them flows logically from them having been individually taught in prior art.
With respect to claims 2-3, 6, 10 and 154, Perrin et al. teach that the CTLA4-lg fusion protein is abatacept (claim 22), which comprises instant SEQ ID NO: 1. Note that Applicants stated that abatacept reads on claim 154.
With respect to claims 11 and 16-17, as discussed above, Camu et al. teach administering aldesleukin (title; abstract; passim), which comprises instant SEQ ID NO: 3.
With respect to claim 18, Perrin et al. and Camu et al. teach subcutaneous administration (Perrin et al. at para [0046]; Camu et al. at para 2.3).
With respect to claims 26 and 156, Camu et al. teach administering aldesleukin once daily for 5 days (abstract).
With respect to claims 31, 35, 42, 46, 50, 75, 93, 97, 155 and 157-158, the MPEP 2144.05 A states that “[G]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)”.
Since Applicant has not disclosed that the specific limitations recited in the instant claims are for any particular purpose or solve any stated problem, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable dosage and time interval between dosages by normal optimization procedures known in the pharmaceutical art.
With respect to claim 159, Perrin et al. teach subcutaneous administration (para [0046]).
Claim(s) 1-3, 6, 10-11, 16-18, 26, 31, 35, 42, 46, 50, 75, 93, 97, 103, 106 and 154-159 are rejected under 35 U.S.C. 103 as being unpatentable over Perrin et al. (WO 2010/065819, previously cited) in view of Camu et al. (EBioMedicine 59 (2020) 102844, previously cited) as applied to claims 1-3, 6, 10-11, 16-18, 26, 31, 35, 42, 46, 50, 75, 93, 97, 103 and 154-159 above, and further in view of Ranieri et al. (Front Neurol. 2021 Feb 5;11:605335).
The teachings of Perrin et al. and Camu et al. with respect to claims 1-3, 6, 10-11, 16-18, 26, 31, 35, 42, 46, 50, 75, 93, 97, 103 and 154-159 have been discussed above.
Perrin et al. and Camu et al. do not teach that the method further comprises performing an additional therapeutic intervention.
Ranieri et al. teach that “[I]n the last 20 years, several modalities of neuromodulation, mainly based on non-invasive brain stimulation (NIBS) techniques, have been tested as a non-pharmacological therapeutic approach to slow disease progression in amyotrophic lateral sclerosis (ALS)……. Corticospinal excitability can be suppressed or enhanced using NIBS techniques, namely, repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), as well as invasive brain and spinal stimulation. Experimental evidence supports the hypothesis that the after-effects of NIBS are mediated by long-term potentiation (LTP)-/long-term depression (LTD)-like mechanisms of modulation of synaptic activity, with different biological and physiological mechanisms underlying the effects of tDCS and rTMS and, possibly, of different rTMS protocols. This potential has led to several small trials testing different stimulation interventions to antagonize excitotoxicity in ALS. Overall, these studies suggest a possible efficacy of neuromodulation in determining a slight reduction of disease progression, related to the type, duration, and frequency of treatment” (abstract).
Ranieri et al. also teach that “[S]ubjects in the early stages of disease, stratified based on clinical characteristics and biomarkers, could represent a population exhibiting less variability and more likely to benefit of the potential disease modifying effect of brain stimulation interventions” (page 15, right column, 7th para).
Therefore, since the references teach that abatacept, aldesleukin and invasive and non-invasive brain stimulation techniques are effective in treating amyotrophic lateral sclerosis, it would have been obvious, with a reasonable expectation of success, to include invasive and/or non-invasive brain stimulation techniques in the method obvious over Perrin et al. and Camu et al.
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 1-3, 6, 10-11, 16-18, 26, 31, 35, 42, 46, 50, 75, 93, 97, 103 and 154-159 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15-18, 21, 23, 27, 29, 33, 35, 39, 47-49, 65, 67-68 and 82-86 of copending Application No. 18692235 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they relate to the same method.
With respect to claims 1 and 103, ‘235 teaches a method of treating ALS comprising administering a CTLA-4 fusion protein and IL-2 (claims 27 and 33).
With respect to claims 2-3, 6, 10 and 154, ‘235 teaches that the CTLA-4 fusion protein is abatacept (claim 84), which comprises instant SEQ ID NO: 1. Note that Applicants stated that abatacept reads on claim 154.
With respect to claims 11 and 16-17, ‘235 teaches that the IL-2 is aldesleukin (paras [0081], [0087], [0113], [0196], [0246], [0251] and [0256]), which comprises instant SEQ ID NO: 3. Please note that it is proper to turn to and rely on the disclosure of a patent application to ascertain what constitutes an obvious modification. This position is supported by the courts. See In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970).
With respect to claim 18, ‘235 teaches subcutaneous administration (paras [0206], [0260] and [0292]).
With respect to claims 26 and 156, ‘235 teaches administering the IL-2 (i.e. aldesleukin) once daily for 5 days (para [0292]).
With respect to claims 31, 35, 42, 46, 50, 75, 93, 97, 155 and 157-158, the MPEP 2144.05 A states that “[G]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)”.
Since Applicant has not disclosed that the specific limitations recited in the instant claims are for any particular purpose or solve any stated problem, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable dosage and time interval between dosages by normal optimization procedures known in the pharmaceutical art.
With respect to claim 159, ‘235 teaches subcutaneous administration (paras [0206], [0260] and [0292]).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-3, 6, 10-11, 16-18, 26, 31, 35, 42, 46, 50, 75, 93, 97, 103, 106 and 154-159 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15-18, 21, 23, 27, 29, 33, 35, 39, 47-49, 65, 67-68 and 82-86 of copending Application No. 18692235 in view of Ranieri et al. (Front Neurol. 2021 Feb 5;11:605335).
The teachings of ‘235 with respect to claims 1-3, 6, 10-11, 16-18, 26, 31, 35, 42, 46, 50, 75, 93, 97, 103 and 154-159 have been discussed above.
‘235 does not teach that the method further comprises performing an additional therapeutic intervention.
Ranieri et al. teach that “[I]n the last 20 years, several modalities of neuromodulation, mainly based on non-invasive brain stimulation (NIBS) techniques, have been tested as a non-pharmacological therapeutic approach to slow disease progression in amyotrophic lateral sclerosis (ALS)……. Corticospinal excitability can be suppressed or enhanced using NIBS techniques, namely, repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), as well as invasive brain and spinal stimulation. Experimental evidence supports the hypothesis that the after-effects of NIBS are mediated by long-term potentiation (LTP)-/long-term depression (LTD)-like mechanisms of modulation of synaptic activity, with different biological and physiological mechanisms underlying the effects of tDCS and rTMS and, possibly, of different rTMS protocols. This potential has led to several small trials testing different stimulation interventions to antagonize excitotoxicity in ALS. Overall, these studies suggest a possible efficacy of neuromodulation in determining a slight reduction of disease progression, related to the type, duration, and frequency of treatment” (abstract).
Ranieri et al. also teach that “[S]ubjects in the early stages of disease, stratified based on clinical characteristics and biomarkers, could represent a population exhibiting less variability and more likely to benefit of the potential disease modifying effect of brain stimulation interventions” (page 15, right column, 7th para).
Therefore, since the references teach that abatacept, aldesleukin and invasive and non-invasive brain stimulation techniques are effective in treating amyotrophic lateral sclerosis, it would have been obvious, with a reasonable expectation of success, to include invasive and/or non-invasive brain stimulation techniques in the method obvious over ‘235.
This is a provisional nonstatutory double patenting rejection.
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/SERGIO COFFA Ph.D./
Primary Examiner
Art Unit 1658
/SERGIO COFFA/Primary Examiner, Art Unit 1658
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