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 .
Priority
This application is a 371 of PCT/US2019/046431, filed Aug. 12, 2019, and claims priority benefit of U.S. Provisional Application no. 62/718,088, filed Aug. 13, 2018.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114 was filed in this application after appeal to the Patent Trial and Appeal Board, but prior to a decision on the appeal. Since this application is eligible for continued examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on Mar. 2, 2026 has been entered.
Claim Status
Claims 5-14 and 25-29 are currently pending and subject to examination.
Claim Rejections - 35 USC § 103- Previously Presented
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.
The rejection of claims 5-14 and 25-29 under 35 U.S.C. 103 as being unpatentable over Baudry et al. (WO 2016/077461, published May 16 2016) is maintained.
Response to Arguments
The Applicant argues that the generic disclosure cannot substantiate the rejection of the specific compounds of claims 5-6 and that Baudry discloses distinct structures from that which is claimed. These arguments were fully considered but are not persuasive. Baudry discloses a genus which encompasses the claimed compounds and subgenus, as shown in the prior action. Baudry also discloses very similar specific species to the claimed species, as shown in the prior action. The compounds of Baudry differ from the claimed compounds by a bioisosteric substitution: divalent O for divalent C and by the regular addition of the same chemical group (methoxy) or substitution of F for methoxy which is within the scope of Baudry. The scope and content of the prior art render the claimed species obvious as a whole over the prior art. (See MPEP 2144.08 (discussing the obviousness of species when the prior art teaches a genus)).
The Applicant fails to overcome the prima facie case of obviousness by presenting unexpected results. The claimed compounds are structurally and functionally similar to the prior art compounds and the Applicant has not demonstrated that they offer any advantages over the prior art compounds that could rebut the prima facie case of obviousness.
Reiterated Rejection
Claim 5 is directed towards a compound that is compound 17 having the following structure:
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.
Baudry teaches the following compound as a calpain inhibitor:
“In certain embodiments, a selective inhibitor of calpain-2 according to the invention is a molecule based on the following structure of Formula I:
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.”
Baudry et al., Specification, pages 23-24, paragraph 087.
[AltContent: oval][AltContent: oval] This compound differs from the claimed compounds in two sites. There is carbamate instead of an amide and there is a different substituent on the terminal phenyl at one site:
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.
One of ordinary skill in the art, however, would have a reasonable expectation of success to perform the substitutions and obtain a compound with similar properties to the compounds of Baudry because these art well known bioisosteric replacements which are contemplated by Baudry.
For example, see the generic disclosure of Baudry:
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Baudry et al., Specification, page 21, paragraph 085.
As in compound 17, Baudry et al. teach M1 is -C substituted to link a blocking group such as Y1-PhCH2-, wherein Y1 is H, in the selective inhibitor of calpain-2 shown above (Baudry et al., page 21, paragraph 085).
As in compound 17, Baudry et al. teach that X1 is C6H3(3,5-R4,R5) wherein R4 is H and R5 is -OCH3 (Baudry et al., page 22, paragraph 085).
Bioisosteric replacements such as diavalent C to divalent O and the regular addition of the same chemical group is prima facie obviousness given close structural and functional similarities:
III. PRESENCE OF A TRUE HOMOLOGOUS OR ISOMERIC RELATIONSHIP IS NOT CONTROLLING
Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In rePayne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979) (Claimed and prior art compounds were both directed to heterocyclic carbamoyloximino compounds having pesticidal activity. The only structural difference between the claimed and prior art compounds was that the ring structures of the claimed compounds had two carbon atoms between two sulfur atoms whereas the prior art ring structures had either one or three carbon atoms between two sulfur atoms. The court held that although the prior art compounds were not true homologs or isomers of the claimed compounds, the similarity between the chemical structures and properties is sufficiently close that one of ordinary skill in the art would have been motivated to make the claimed compounds in searching for new pesticides.).
See also In re Mayne, 104 F.3d 1339, 41 USPQ2d 1451 (Fed. Cir. 1997) (claimed protein was held to be obvious in light of structural similarities to the prior art, including known structural and functional similarity of the amino acids leucine and isoleucine); In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (claimed and prior art compounds used in a method of treating depression would have been expected to have similar activity because the structural difference between the compounds involved a known bioisosteric replacement); In reDillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990) (The tri-orthoester fuel compositions of the prior art and the claimed tetra-orthoester fuel compositions would have been expected to have similar properties based on close structural and chemical similarity between the orthoesters and the fact that both the prior art and applicant used the orthoesters as fuel additives.) (See MPEP § 2144 for a more detailed discussion of the facts in the Dillon case.).
As such, claim 5 was prima facie obvious at the time of filing.
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Claim 6 is directed towards a compound that is compound 15 of the following structure:
.
Baudry teaches the following compound as a calpain inhibitor:
“In certain embodiments, a selective inhibitor of calpain-2 according to the invention is a molecule based on the following structure of Formula I:
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.”
Baudry et al., Specification, pages 23-24, paragraph 087.
The above compound has a carbamate instead of an amide and methoxy group on the terminal phenyl in place of fluorine. one of ordinary skill in the art would have a reasonable expectation of success to obtain the compound 15 of claim 6 because these modifications are bioisosteric replacements which are expressly contemplated by the generic disclosure of Baudry.
For example: Baudry et al. teach compounds of Formula (I), including compounds 15 and 17, as calpain inhibitors, as in the instant invention:
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Baudry et al., Specification, page 21, paragraph 085.
As in compound 15, Baudry et al. teach M1 is -C substituted to link a blocking group such as Y1-PhCH2-, wherein Y1 is H, in the selective inhibitor of calpain-2 shown above (Baudry et al., page 21, paragraph 085).
As in compound 15, Baudry et al. teach that X1 is C6H3(3,5-R4,R5) wherein R4 is F and R5 is -OCH3 (Baudry et al., page 22, paragraph 085).
As such, claim 6 was prima facie obvious at the time of filing.
Claim 7 is directed towards a compound of claim 5, wherein the compound is a racemate. One of ordinary skill in the art would have a reasonable expectation of success to generate a compound of claim 5, wherein the compound is a racemate because Baudry teaches similar racemates:
“In certain embodiments, a selective inhibitor of calpain-2 according to the invention is a molecule based on the following structure of Formula I:
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wherein the chiral center 1 indicated by the circle is Levorotary (L), and wherein the chiral center 2 is D- or L-, or a racemic mixture. Two embodiments of the molecule of Formula 1 are purified forms having an L- at chiral center 1 and an L- form at chiral center 2, or separately an L-form at chiral center 1 and a D-form at chiral center 2.”
Baudry et al., Specification, pages 23-24, paragraph 087 (emphasis added).
Therefore, claim 7 was prima facie obvious at the time of filing.
Claim 8 is directed towards an optically enriched mixture of a compound of claim 5. ne of ordinary skill in the art would have a reasonable expectation of success to obtain an optically enriched mixture of a compound of formula (I) because as shown above in the rejection of claim 8, Baudry et al. teach that it is possible to obtain two optically pure forms of a similar compound (Baudry et al., Specification, pages 23-24, paragraph 087).
Therefore, claim 8 was prima facie obvious at the time of filing.
Claim 9 is directed towards a pharmaceutical composition comprising the compound of claim 5 and a pharmaceutically acceptable excipient.
One of ordinary skill in the art would have a reasonable expectation of success to obtain a pharmaceutical composition comprising a compound of formula (I) because Baudry et al. teach pharmaceutical compositions comprising similar compounds and pharmaceutically acceptable excipients:
“Described herein, are compositions and methods related to isoform-selective calpain inhibitors. Isoform-selective inhibitors are directed at either calpain-1 or calpain-2, and thus, selectively reduce the activity of one isoform in comparison to the other.”
Baudry et al., Specification, page 2, paragraph 006 (emphasis added).
“The pharmaceutical compositions of the invention may be prepared by methods known in the pharmaceutical formulation art, for example, see Remington's Pharmaceutical Sciences, 22nd Ed., (Pharmaceutical Press, 2012), which is incorporated herein by reference. In a solid dosage form, a compound of the invention may be admixed with at least one pharmaceutically acceptable excipient such as, for example, sodium citrate or dicalcium phosphate…”
Baudry et al., Specification, page 43, paragraph 0123 (emphasis added).
Thus, claim 9 was prima facie obvious at the time of filing.
Claim 10 is directed towards a method of treating glaucoma related nerve damage comprising administering a compound of claim 5 to a patient. One of ordinary skill in the art would have a reasonable expectation of success to treat glaucoma related nerve damage with the compound of claim 5 because Baudry et al. teach that calpain-2 inhibitors of their invention are useful for treating nerve degeneration related to glaucoma:
“Calpain-2 selective inhibitors are neuroprotective in cultured neurons and enhance Long-term potentiation (LTP), a cellular model of learning and memory, in acute hippocampal slices. Calpain 2 inhibitors are useful as methods of enhancing LTP, and methods of enhancing LTP consolidation. Calpain-2 inhibitors according to the invention are useful for improving learning and reducing neurodegeneration. Therefore, they are expected to be used effectively for treatments of diseases related to synaptic dysfunction, synaptic degeneration, or neurodegeneration, including idiotypic and familial forms of Alzheimer's disease and Parkinson's disease, and dementia, Huntington's disease, Amyotropic Lateral Sclerosis (ALS), seizure, encephalitis, stroke, vasospasm, hypovolemic shock, traumatic shock, traumatic brain injury, reperfusion injury, multiple sclerosis, AIDS related dementia, neurotoxicity, head trauma, and spinal cord injury, glaucoma, open-angle glaucoma, angle-closure glaucoma, normal tension glaucoma, congenital glaucoma, pigmentary glaucoma, pseudoexfoliative glaucoma, traumatic glaucoma, neovascular glaucoma, irido corneal endothelial syndrome, ischemia in the eye, ischemia in the retina.”
Baudry et al., Specification, page 42, paragraph 0118.
Therefore, claim 10 was prima facie obvious at the time of filing.
Claim 11 is directed towards the treatment of a patient suffering from an eye disorder by administering to the patient an effective amount of a compound of claim 5. One of ordinary skill in the art would have a reasonable expectation of success to treat an eye disorder with a compound of formula (I) because as shown in the rejection of claim 10, Baudry et al. teach the treatment of eye disorders using a similar compounds.
Therefore, claim 11 was prima facie obvious at the time of filing.
Claim 12 is directed towards the method of claim 11 wherein the eye disorder is retinal cell death. One of ordinary skill in the art would have a reasonable expectation of success to treat retinal cell death with a compound of claim 5 Baudry et al. teach that similar calpain-2 inhibitors are protective against retinal cell death:
“Example 11: Calpain-1 and calpain-2 play opposite roles in RGC death induced by acute lOP elevation. To evaluate elevated lOP-induced retinal damage, lOP of the right eye was elevated to 110 mm Hg for 60 min, while a sham procedure was performed in the left eye. Retinal sections were collected for H&E staining 3 days after surgery (Fig. 11A and B). In WT mice injected (i.p.) with vehicle (10% DMSO in PBS), cell counts in right GCL were 62.1 ± 5.6 cells/mm, as compared to 113.4 ± 7.1 cells/mm in the left eye (n = 7). We used three different protocols to examine the effect of C2I. First, C2I (0.3 mg/kg) was injected (i.p.) 30 min before and 2 h after acute lOP elevation (pre and post inj). Cell counts in GCL of sham eye and IOP- elevated eye were 125.1 + 10.5 and 105.8 ± 4.5 cells/mm, respectively (n = 3, no significant difference (ns) sham vs. IOP). Second, C2I was injected (i.p.) 2 h after lOP elevation (one post inj). Cell counts in sham and IOP-elevated eye were 110.6 ± 3.6 and 86.4 ± 7.0 cells/mm (n = 10, ns). Third, C2I was injected (i.p.) 2 and 4 h after IOP elevation (two post inj). Cell counts in sham and IOP-elevated eye were 118.6 ± 3.7 and 96.1 ± 6.3 cells/mm (n = 6, ns). In all three C2I- injected groups, cell survival rate (ratio of cell count in IOP-elevated eye to that in sham eye) was significantly increased, as compared to vehicle-injected group (Fig. 11C). These results suggest that calpain-2 activation plays an important role in GCL cell death after IOP elevation and that C2I systemic injection has a protective effect against lOP-induced cell death.”
Baudry et al., Specification, page 51, paragraph 0145 (emphasis added).
Therefore, claim 12 was prima facie obvious at the time of filing.
Claim 13 is directed towards the method of claim 11 wherein the patient is suffering from glaucoma. The rejection of claim 10 is incorporated herein by reference.
As such, claim 13 was prima facie obvious at the time of filing.
Claim 25 is directed towards treating glaucoma related nerve damage in a patient comprising administering an effective amount of a compound of claim 6.
One of ordinary skill in the art would have a reasonable expectation of success to treat glaucoma related nerve damage with this method because Baudry et al. teach that calpain-2 inhibitors of their invention are useful for treating nerve degeneration related to glaucoma:
“Calpain-2 selective inhibitors are neuroprotective in cultured neurons and enhance Long-term potentiation (LTP), a cellular model of learning and memory, in acute hippocampal slices. Calpain 2 inhibitors are useful as methods of enhancing LTP, and methods of enhancing LTP consolidation. Calpain-2 inhibitors according to the invention are useful for improving learning and reducing neurodegeneration. Therefore, they are expected to be used effectively for treatments of diseases related to synaptic dysfunction, synaptic degeneration, or neurodegeneration, including idiotypic and familial forms of Alzheimer's disease and Parkinson's disease, and dementia, Huntington's disease, Amyotropic Lateral Sclerosis (ALS), seizure, encephalitis, stroke, vasospasm, hypovolemic shock, traumatic shock, traumatic brain injury, reperfusion injury, multiple sclerosis, AIDS related dementia, neurotoxicity, head trauma, and spinal cord injury, glaucoma, open-angle glaucoma, angle-closure glaucoma, normal tension glaucoma, congenital glaucoma, pigmentary glaucoma, pseudoexfoliative glaucoma, traumatic glaucoma, neovascular glaucoma, irido corneal endothelial syndrome, ischemia in the eye, ischemia in the retina.”
Baudry et al., Specification, page 42, paragraph 0118.
Therefore, claim 25 was prima facie obvious at the time of filing.
Claims 26 are directed towards a method of treating an eye disorder comprising administering an effective amount of the compound of claim 6. One of ordinary skill in the art would have a reasonable expectation of success to treat eye disorders with compounds 15 and 17 because as shown above in the rejection of claim 25, Baudry teaches that similar calpain inhibitors treat eye disorders. Therefore, claim 26 was prima facie obvious at the time of filing.
Claims 27 is directed towards the methods of claim 25, wherein the eye disorder is retinal neuronal cell death.
One of ordinary skill in the art would have a reasonable expectation of success to treat retinal cell death with the compounds 15 and 17 because Baudry et al. teach that similar calpain-2 inhibitors are protective against retinal cell death:
“Example 11: Calpain-1 and calpain-2 play opposite roles in RGC death induced by acute lOP elevation. To evaluate elevated lOP-induced retinal damage, lOP of the right eye was elevated to 110 mm Hg for 60 min, while a sham procedure was performed in the left eye. Retinal sections were collected for H&E staining 3 days after surgery (Fig. 11A and B). In WT mice injected (i.p.) with vehicle (10% DMSO in PBS), cell counts in right GCL were 62.1 ± 5.6 cells/mm, as compared to 113.4 ± 7.1 cells/mm in the left eye (n = 7). We used three different protocols to examine the effect of C2I. First, C2I (0.3 mg/kg) was injected (i.p.) 30 min before and 2 h after acute lOP elevation (pre and post inj). Cell counts in GCL of sham eye and IOP- elevated eye were 125.1 + 10.5 and 105.8 ± 4.5 cells/mm, respectively (n = 3, no significant difference (ns) sham vs. IOP). Second, C2I was injected (i.p.) 2 h after lOP elevation (one post inj). Cell counts in sham and IOP-elevated eye were 110.6 ± 3.6 and 86.4 ± 7.0 cells/mm (n = 10, ns). Third, C2I was injected (i.p.) 2 and 4 h after IOP elevation (two post inj). Cell counts in sham and IOP-elevated eye were 118.6 ± 3.7 and 96.1 ± 6.3 cells/mm (n = 6, ns). In all three C2I- injected groups, cell survival rate (ratio of cell count in IOP-elevated eye to that in sham eye) was significantly increased, as compared to vehicle-injected group (Fig. 11C). These results suggest that calpain-2 activation plays an important role in GCL cell death after IOP elevation and that C2I systemic injection has a protective effect against lOP-induced cell death.”
Baudry et al., Specification, page 51, paragraph 0145 (emphasis added).
Thus, claim 27 was prima facie obvious at the time of filing.
Claim 28 is directed towards the method of claim 25 respectively, wherein the subject is suffering from glaucoma. One of ordinary skill in the art would have a reasonable expectation of success to apply the method to patients suffering from glaucoma because as shown in the rejection of claims 25, Baudry teaches the treatment of glaucoma with similar calpain inhibitors. Therefore, claim 28 was prima facie obvious at the time of filing.
Claim 14 and 29 are directed towards the methods claims 10 and 25 respectively, wherein the compound is administered via a method selected from intravitreal injection, intraocular injection, intraocular perfusion, periocular injection and sub-Tenon injection.
One of ordinary skill in the art would have a reasonable expectation of success to administer the compounds via these methods because Baudry et al. teach the intravitreal injection of similar calpain-2 inhibitors (C2I):
“ Example 12: Intravitreal injection of C2l reduces cell death in GCL and prevents loss of vision caused by acute IOP elevation. We used intravitreal C2I injection in order to locally deliver C2I to retina. First, we tested the delivery efficiency by injecting different doses of C2I intravitreally 2 h after lOP elevation in calpain-1 KO mice and analyzing SBDP levels in IPL at 4 h (Fig. 12A and B). A clear dose-dependent inhibition of SBDP formation was observed, providing an apparent IC50 of 8 μΜ for C2I. In all subsequent experiments, 20 μΜ (1 μΙ) was used to examine the neuroprotective effects of intravitreal C2I injection. Eyes were collected 3 days after surgery for H&E staining. After vehicle injection (10% DMSO in PBS), RGC counts in sham eye and lOP-elevated eye were 132.3 ± 4.5 and 62.0 ± 5.7 cells/mm (p < 0.001 sham vs. IOP, n = 4). In C2l-treated eyes, RGC counts in sham eye and lOP-elevated eyes were 128.1 ± 7.2 and 101.3 ± 9.2 cells/mm (no significant difference, sham vs. IOP, n = 5) (Fig. 12C and D). Survival rate with C2I injection was significantly improved, as compared to vehicle injection (80.8 ± 8.4 % vs. 47.2 ± 5.4 %, p < 0.01) (Fig. 5e), suggesting that intravitreal C2I injection 2 h after IOP elevation is neuroprotective against lOP-induced cell death in GCL.”
Baudry et al., Specification, pages 52-53, paragraph 0149 (emphasis added).
Therefore, claims 14 and 29 were prima facie obvious at the time of filing.
In light of the above teachings, the invention as a whole was prima facie obvious at the time of filing.
Double Patenting- Previously Presented
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.
The provisional rejection of claims 5-6 on the ground of nonstatutory double patenting as being unpatentable over claim 18 of copending Application No. 17/904,208 (herein referred to as ‘208) (reference application) is maintained.
Response to Arguments
The Applicant does not present arguments relevant to this rejection. Therefore, the rejection is maintained.
Reiterated Rejection
Although the claims at issue are not identical, they are not patentably distinct from each other because the genus of claim 18 encompasses the claimed species with sufficient specificity.
Claim 5 is directed towards compound 17 and claim 6 is directed towards compound 15:
Claim 18 of ‘208 is directed towards a compound of Formula (XIII):
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‘208, claim 18.
As in the instantly preferred compounds above, claim 18 of ‘208 teaches that L1 is alkylene and L2 is [amino] alkylene, A is phenyl, R1 can be absent when n is 0, R2 is alkyl, R6 is halogen or C1-6alkoxy, and k is an integer from 0-6.
Therefore, claims 5-6 are provisionally rejected on the ground of nonstatutory double patenting.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The provisional rejection of claims 5-13 and 25-28 on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 9-16, and 18-22 of copending Application No. 17/904,208 (herein referred to as ‘208) in view of Sanders and Donkor (Bioorganic & Medicinal Chemistry Letters, 2006, Volume 16, Issue 7, pages 1965-1968, Published April 1, 2006) is maintained.
The rejection of claims 15-20 is withdrawn as moot because these claims were cancelled.
Response to Arguments
The Applicant argues that the present claims do not require a urea group as in the reference application. The Applicant cites In re Grabiak where the disclosure of an ester was found to not render obvious a thioester in the absence of a reference suggesting the change of a thioester of an ester group (Remarks, page 9). These arguments were fully considered but are not persuasive. The Examiner cites Sanders and Donkor, which is a reference suggesting the modification from urea to peptide aldehyde. Therefore, the rejection is maintained.
Reiterated Rejection
Claim 5 is directed towards the compound:
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Specification, page 4.
Claim 1 of ‘208 is directed towards a compound of Formula (X):
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‘208, Claim 1.
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‘208 gives the following as the preferred embodiment of a compound of Formula (I) of claim 1:
‘208, claim 12.
These compounds are so similar that one of ordinary skill in the art would expect them to have similar properties. Compound 17 differs from the preferred embodiment of Formula (I) of claim 1 of ‘208 by the use of alkyl bridge (e.g.
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) instead of a urea dipeptide linkage in the ‘208 compound (e.g.
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) and there is an additional methoxy substituent on the ‘208 compound. For the latter difference, in claim 16, ‘208 teaches that this additional methoxy is optional; “k is an integer from 0 to 12” (‘208, claim 16). For the former difference, both types of peptidomimetics are commonly known in the art to be functional calpain inhibitors and thus one of ordinary skill in the art would expect the claimed compounds and the compounds of ’208 to have similar properties. For example, see the teachings of Sanders and Donkor:
“A series of peptide aldehyde derivatives in which the P2 chiral carbon has been replaced with nitrogen were synthesized as urea-based peptidomimetic inhibitors of µ-calpain. The compounds mirrored the general SAR of peptidyl aldehyde calpain inhibitors but displayed greater selectivity for µ-calpain over cathepsin B.”
Sanders and Donkor, Abstract;
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Sanders and Donkor, Figure 1, page 2.
Therefore, claim 5 is obvious over claims 1, 12, and 16 of ‘208 in view of Sanders and Donkor and is rejected on the ground of nonstatutory double patenting.
Claim 6 is directed towards compound 15:
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Claim 6.
Claim 16 of ‘208 is directed towards a compound of Formula (X):
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‘208, Claim 16.
Claim 19 of ‘208 gives the following as the preferred embodiment of a compound of Formula (X) of claim 16:
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‘208, claim 19.
These preferred compounds of instant claim 6 and ‘208 claim 19 are so similar that one of ordinary skill in the art would expect them to have similar properties. Both compounds contain methoxy and halogen substituents and claim 16 teaches that the position of the substituents is not critical for activity, and regardless, ring-hopping is generally not expected to substantially alter the properties of a compound:
“Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril.).”
MPEP § 2144.09, subsection II, [R-07.2022].
Additionally, as shown above, both alkyl bridged and urea derivatized peptidomimetics are commonly known in the art, and as such the instantly claimed compound and the ‘208 compound would be expected to have similar properties. For example, see the teachings of Sanders and Donkor:
“A series of peptide aldehyde derivatives in which the P2 chiral carbon has been replaced with nitrogen were synthesized as urea-based peptidomimetic inhibitors of µ-calpain. The compounds mirrored the general SAR of peptidyl aldehyde calpain inhibitors but displayed greater selectivity for µ-calpain over cathepsin B.”
Sanders and Donkor, Abstract;
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Sanders and Donkor, Figure 1, page 2.
As such, claim 6 is rejected on the ground of nonstatutory double patenting.
Claim 7 is directed towards “a compound of claim 5 wherein the compound is a racemate.” Claim 13 of ‘208 also teaches a racemate.
Therefore, claim 7 is rejected on the ground of non-statutory double patenting.
Claim 8 is directed towards “a compound of claim 5 wherein the compound is an optically enriched mixture.” Claim 14 of ‘208 also teaches an optically enriched mixture.
Therefore, claim 8 is rejected on the ground of non-statutory double patenting.
Claim 9 is directed towards “a pharmaceutical composition comprising the compound of claim 5 and a pharmaceutically acceptable excipient”. Claim 20 of ‘208 also teaches a pharmaceutical composition of the compound of claim 1 of ‘208 and a pharmaceutically acceptable excipient.
Therefore, claim 9 is rejected on the ground of non-statutory double patenting.
Claim 10 is directed towards:
“a method of treating glaucoma-related nerve damage in a patient, said method comprising administering to a patient in need thereof an effective amount of a compound or composition of any one of claims 1 through 9.”
Claim 10.
Claim 11 is directed towards “A method of treating a subject suffering from an eye disorder, comprising: administering to the subject an effective amount of a compound or composition of claim 5”.
Claim 12 is directed towards: “ The method of claim 11 wherein the eye disorder is associated with retinal neuronal cell death.
Claim 13 is directed towards: The method of claim 11 wherein the subject is suffering from glaucoma.
Claim 22 of ‘208 is directed towards:
“A method of treating a subject suffering from a disorder or symptom associated with neuronal cell death, comprising administering to the subject an effective amount of a compound or composition of claim 1”
‘208, claim 22.
Because claim 22 of ‘208 teaches that these compounds are effective against nerve damage, one of ordinary skill in the art would be motivated to, and have a reasonable expectation of success of treating eye disorders associated with neuronal cell death with the compounds of the instant invention, shown above to be reasonably expected to have similar properties to the compounds of ‘208.
Claims 21-28 are directed towards the same conditions as claims 10-13, but recite compound 15 instead of compound 17. As compound 15 and 17 are obvious over the disclosure of ‘208 in view of Sanders and Donkor as explained above, these method claims are also obvious for the reasons given in the rejection of claims 10-13.
Therefore, claims 10-13 and 21-28 are rejected on the ground of non-statutory double patenting.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The provisional rejection of claims 14 and 29 on the ground of nonstatutory double patenting as being unpatentable over claim 22 of copending Application No. 17/904,208 (herein referred to as ‘208) in view of Sanders and Donkor (Bioorganic & Medicinal Chemistry Letters, 2006, Volume 16, Issue 7, pages 1965-1968, Published April 1, 2006) and Pang et al. (US 6,303,579 B1, Granted October 16, 2001) is maintained.
Response to Arguments
The arguments presented above are incorporated herein by reference. This claim is merely a method claim and the Applicant does not present specific arguments directed towards this method, but rather to the compounds as mentioned above.
Reiterated Rejection
Claim 14 is directed towards:
“the method of claim 10 wherein the compound or composition is administered via a method selected from the group consisting of intravitreal injection, intraocular injection, intraocular perfusion, periocular injection and sub-Tenon injection.”
Claim 14.
Claim 29 is directed towards:
“the method of claim 25 wherein the compound or composition is administered via a method selected from the group consisting of intravitreal injection, intraocular injection, intraocular perfusion, periocular injection and sub-Tenon injection.”
The rejection of claims 1-2, and 4-13 and 15-20 on the ground of nonstatutory double patenting over ‘208 in view of Sanders and Donkor is incorporated herein by reference. Claim 22 of ‘208, as previously stated, teaches a method of treating a subject suffering from a disorder or symptom associated with neuronal cell death. Pang et al. teaches that calpain inhibitors are useful against neuronal cell death associated with eye diseases such as glaucoma, and can be administered through intraocular injection (Pang et al., column 4, line 67).
Therefore, claims 14 and 29 are provisionally rejected on the ground of nonstatutory double patenting.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is found to be allowable.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 HEATHER DAHLIN whose telephone number is (571)270-0436. The examiner can normally be reached 9-5.
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/HEATHER DAHLIN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629