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 .1
Status of Claims
Claims 1, 9, 11, 14, 15, 17-21, 23, and 30-34 are pending and under examination as being directed to the species of pregabalin, normal tension glaucoma and the formulation of paragraph 188, elected without traverse on July 2, 2024.
PNG
media_image1.png
337
727
media_image1.png
Greyscale
Response to Arguments
Applicant's arguments filed July 16, 2025 have been fully considered but they are not persuasive with regard to the obviousness rejection of claims 1, 9, 11, 14-15, 17-21, 23, and 30-34 over Ibrahim in view of Shields. In response to the amendment of claim 1, the obviousness rejection is modified with Song and Caprioli, detailed below.
New Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicants are advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1, 9, 11, 14-15, 17-21, 23, and 30-34 are rejected under 35 U.S.C. 103 as being unpatentable over Ibrahim et al. Once Daily Pregabalin Eye Drops for Management of Glaucoma ACS Nano. 2019 Dec 24; 13(12): 13728–13744, Published online 2019 Nov18. doi: 10.1021/acsnano.9b07214, provided as cite no. C4 in IDS dates 2/5/2024) in view of Shields, “Normal-tension glaucoma: is it different from primary open-angle glaucoma?” Current Opinion in Ophthalmology 2008, 19:85–88 2008 (provided on PTO-892 form dated 8/26/2024) as evidenced by Song BJ and Caprioli J. New directions in the treatment of normal tension glaucoma. Indian J Ophthalmol 2014;62:529-37. Song and Caprioli is cited on the PTO-892 form.
Claim 1 is directed to a method of treating glaucoma in a subject in need thereof, the method comprising administering to the subject an effective amount of an ocular composition comprising pregabalin, wherein the glaucoma is normal tension glaucoma, and the subject's glaucoma progression is not responsive to intraocular pressure (IOP) lowering.
In terms of claim interpretation, the claimed method requires
administration of pregabalin in effective amounts
to a specific patient in need, one afflicted with glaucoma, in particular normal tension glaucoma, not responsive to IOP lowering.
Regarding claim 1 and the limitations of treatment of glaucoma with a pharmaceutical composition comprising pregabalin, Ibrahim discloses a pharmaceutical composition (noted to be a multilayered microemulsion) comprising pregabalin, for the treatment of glaucoma, see multiple instances, including abstract; Results and Discussion Section starting at page 13729, column 2, disclosing treatment of primary open angle glaucoma, POAG, with a pregabalin (PRG) water in oil in water (W/O/W) microemulsion eye drops comprising various ingredients including Labrafac Oil/Milli-Q water and surfactant or surfactant mixtures such as (A) Capryol 90; (B) Capryol 90/lecithin [1:1]; (C) Capryol 90/lecithin [1:2]; (D) Capryol 90/ lecithin [2:1]; (E) Transcutol P; and (F) Transcutol P/lecithin (1:1)), see Figure 1 page 13730. See also Table 1 on page 13731, reproduced below.
PNG
media_image2.png
281
368
media_image2.png
Greyscale
Regarding a subject in need of treatment (glaucoma), Ibrahim teaches the need to treat patients suffering from primary open angle glaucoma (POAG). See page 13728, see column 1. Ibrahim discloses POAG accounts for 90% of glaucoma cases worldwide, and it is a leading cause of irreversible blindness, Id.
While Ibrahim discloses the claimed pregabalin pharmaceutical composition (W/O/W) for the treatment of glaucoma, such as primary open angle glaucoma (POAG), it does not expressly teach the treatment of normal tension glaucoma (NTG) as claimed.
However, person having of ordinary skill in the art (PHOSITA) would have a reasonable expectation of success in arriving at the claimed invention because NTG is a common form of open-angle glaucoma, including POAG (see Shields 2008 abstract).
Similar to Ibrahim, Shields discloses that NTG and POAG represent a continuum of open-angle glaucoma, in which a certain level of intraocular pressure (IOP) is the predominant causative risk factor in POAG, see abstract.
While teaching IOP control is noted with the treatment of NTG, Shields teaches “[t]here is considerable overlap between the two conditions [NTG and POAG] . . . “, where other non-IOP factors are involved. See abstract.
As evidenced by Song and Caprioli, where the NTG patient is not responsive to the lowering of IOP, Song and Caprioli teach strategies to treat NTG, whether such a patient would be responsive to IOP lowering or not. Along the lines of Shields, Song and Caprioli teach glaucoma can occur at statistically normal IOPs (i.e. NTG patient), i.e., where the claimed subject who a PHOSITA would determine would not be responsive to IOP lowering. See Abstract. Similar to Shields, Song and Caprioli suggest that NTG is likely part of continuum of with POAG due to the clinical overlap. See Abstract.
In particular, with regard to the treatment of NTG, where the patient is not responsive to the lowering of IOP, it is noted that Song and Caprioli, recognizes that while NTG patients are those with statistically normal IOPs, IOP modification is currently the best established target for treatment. See page 533, column 2, Conclusion. Ideally, future treatment of NTG will target both IOP and IOP-independent risk factors. Id. The teaching of use both IOP dependent and IOP-independent risk factors will teach and suggest the treatment of the claimed patient population who is not responsive to IOP lowering.
Song and Caprioli teach “[f]uture research is still needed [thus motivating the PHOSITA] to develop clinically effective and useful IOP-independent neuroprotective agents for NTG.” In fact, Song and Caprioli teach the use of a IOP reducing glaucoma drug, the alpha agonist brimonidine, which has “been shown to be neuroprotective [an IOP-independent mechanism of action] in animal models of optic nerve and retinal injury.” See page 532, column 1, first paragraph. Similarly, a PHOSITA, as evidenced by Song and Caprioli, to look towards IOP lowering drugs in the context of treating NTG not responsive to IOP lowering, where Song and Caprioli teach and suggest such an approach to treat NTG with an IOP-lowering drug, as a research approach to examine a drug’s potential neuroprotective effects in NTG patients not responsive to IOP lowering.
At the time the present application was filed, it would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) following the teachings of Ibrahim to have incorporated the teachings of Shields, as evidenced by Song & Caprioli, in order to treat normal tension glaucoma, as instantly claimed. A PHOSITA would have had a reasonable expectation of success in doing so based on the prior art teaching of treating POAG and NTG by control of intraocular eye pressure as an underlying premise (Ibrahim and Shields), combined with the known method of treating POAG with pregabalin per Ibrahim.
A PHOSITA would treat not only POAG but also NTG patients not responsive to IOP lowering, where such treatment is suggested by Shields & Caprioli, noting approaches to treat NTG with IOP lowering drugs via a non-IOP-lowering mechanism of action, i.e. neuroprotection.
Regarding claim 9 and the limitation of the composition comprising about 0.001% to about 1.2% of pregabalin, Ibrahim discloses a pregabalin W/O/W microemulsion comprising 0.6% pregabalin, see Table 1, page 13731.
Regarding claim 11 requiring topical administration, Ibrahim discloses a topical ophthalmic formulation of pregabalin, see Table 1. See also Figure 3 noting topical application of pregabalin formulations. See also page 13736, column 1 disclosing topical ophthalmic formulations of PRG.
As required by claim 14’s limitation of once a day administration, Ibrahim discloses a pregabalin formulation administered once a day, see page 13736, top of column . See also page 13736, top of column 1, noting statistical analysis of pharmacodynamic parameters (Table 5) illustrates a formulation comprising PRG and its release to prolong corneal contact that is deal for once daily administration.
Claim 15 is directed to the method of claim 1, wherein the composition comprises a microemulsion formulation.
Claim 17 is directed to the method of claim 15, wherein the microemulsion comprises a water-in-oil in- water (W1/O/W 2) multiple microemulsion.
Claim 18 is directed to the method of claim 17, wherein the W1/O/W2 multiple microemulsion comprises:
an internal phase (W 1) comprising an aqueous solution encompassed within in internal emulsifier;
a continuous oil phase (O) encompassing the internal phase and encompassed within an external emulsifier; and
an external aqueous phase (W 2) surrounding the external emulsifier.
Regarding claims 15, 17-18, Ibrahim discloses a pharmaceutical composition (noted to be a multilayered microemulsion) comprising pregabalin, for the treatment of glaucoma, see multiple instances, including abstract; Results and Discussion Section starting at page 13729, column 2, disclosing treatment of primary open angle glaucoma, POAG, with a pregabalin (PRG) water in oil in water (W/O/W) microemulsion eye drops comprising various ingredients including Labrafac Oil/Milli-Q water and surfactant or surfactant mixtures such as (A) Capryol 90; (B) Capryol 90/lecithin [1:1]; (C) Capryol 90/lecithin [1:2]; (D) Capryol 90/ lecithin [2:1]; (E) Transcutol P; and (F) Transcutol P/lecithin (1:1)), see Figure 1 page 13730. See also Table 1 on page 13731, reproduced as detailed above.
Regarding claim 19 wherein the intermediate oil phase comprises an internal emulsifier, Ibrahim discloses internal emulsifiers such as Caproyl 90 and lecithin, see Table 1, page 13731.
Claim 20 is directed to the method of claim 19, wherein the internal emulsifier comprises a surfactant with a hydrophobic-lipophobic balance (HLB) value of 3-7.
Claim 21 is directed to the method of claim 18, wherein the internal emulsifier comprises transcutol P among others.
Regarding claims 20-21, Ibrahim discloses HLB values of W/O microemulsion (ME) and O/W ME are noted to fall withing the range of 3-6 and 8-18, respectively, see page 13730, column 1. Ibrahim discloses choice of surfactants HLB less than equal to 5, such as Capryol 90, lecithin, and transcutol P, Id.
Regarding claim 23, wherein the external aqueous phase comprises a mucoadhesive polymer Ibrahim discloses the use of bioadhesive polymer as strategy for aqueous solution eye drops, see page 13729, column 1. See also Table 1 and page 13731 column 2,noting a bioadhesive polymer(s), such as chitosan, sodium alginate or Carbopol 981.
As required by claim 30 wherein the ocular composition is administered to a subject once daily, twice daily, thrice daily, or once weekly, Ibrahim discloses a pregabalin formulation administered once a day, see page 13736, top of column . See also page 13736, top of column 1, noting statistical analysis of pharmacodynamic parameters (Table 5) illustrates a formulation comprising PRG and its release to prolong corneal contact that is deal for once daily administration.
As required by claim 31 wherein the external emulsifier comprises a surfactant with a HLB value of 10-16, Ibrahim discloses HLB values of W/O microemulsion (ME) and O/W ME are noted to fall withing the range of 3-6 and 8-18, respectively, see page 13730, column 1. Ibrahim discloses during the preparation of the final W/ O/W ME, all the used surfactants, such as Labrasol, tween 80, poloxamer 188, brij 97, and Cremophor EL.
Regarding claim 32 and its recitation of wherein the mucoadhesive polymer is
selected from a group of polyacrylic acid, alginic acid or a salt thereof, chitosan, Ibrahim discloses the use of bioadhesive polymer as strategy for aqueous solution eye drops, see page 13729, column 1. See also Table 1 and page 13731 column 2,noting a bioadhesive polymer(s), such as chitosan, sodium alginate or Carbopol 981 (a known crosslinked polyacrylic acid polymer).
Regarding claim 33 wherein the external aqueous phase further comprises pregabalin, Ibrahim discloses a pharmaceutical composition (noted to be a multilayered microemulsion) comprising pregabalin, for the treatment of glaucoma, see multiple instances, including abstract; Results and Discussion Section starting at page 13729, column 2, disclosing treatment of primary open angle glaucoma, POAG, with a pregabalin (PRG) water in oil in water (W/O/W) microemulsion eye drops comprising various ingredients including Labrafac Oil/Milli-Q water and surfactant or surfactant mixtures such as (A) Capryol 90; (B) Capryol 90/lecithin [1:1]; (C) Capryol 90/lecithin [1:2]; (D) Capryol 90/ lecithin [2:1]; (E) Transcutol P; and (F) Transcutol P/lecithin (1:1)), see Figure 1 page 13730. See also Table 1 on page 13731, where the W/OW microemulsion comprises pregabalin, reproduced above.
Claim 34 is directed to the method of claim 18, wherein: the internal emulsifier comprises a surfactant with a HLB value of 3-7; the external emulsifier comprises a surfactant with a HLB value of 10-16; and the external aqueous phase comprises pregabalin.
Regarding claim 34, Ibrahim discloses HLB values of W/O microemulsion (ME) and O/W ME are noted to fall withing the range of 3-6 and 8-18, respectively, see page 13730, column 1. Ibrahim discloses choice of surfactants HLB less than equal to 5, such as Capryol 90, lecithin, and transcutol P, Id. Regarding claim 34, Ibrahim discloses HLB values of W/O microemulsion (ME) and O/W ME are noted to fall withing the range of 3-6 and 8-18, respectively, see page 13730, column 1. Ibrahim discloses HLB values of W/O microemulsion (ME) and O/W ME are noted to fall withing the range of 3-6 and 8-18, respectively, see page 13730, column 1.
Regarding claim 34, Ibrahim discloses a pharmaceutical composition (noted to be a multilayered microemulsion) comprising pregabalin, for the treatment of glaucoma, see multiple instances, including abstract; Results and Discussion Section starting at page 13729, column 2, disclosing treatment of primary open angle glaucoma, POAG, with a pregabalin (PRG) water in oil in water (W/O/W) microemulsion eye drops comprising various ingredients including Labrafac Oil/Milli-Q water and surfactant or surfactant mixtures such as (A) Capryol 90; (B) Capryol 90/lecithin [1:1]; (C) Capryol 90/lecithin [1:2]; (D) Capryol 90/ lecithin [2:1]; (E) Transcutol P; and (F) Transcutol P/lecithin (1:1)), see Figure 1 page 13730. See also Table 1 on page 13731, where the W/OW microemulsion comprises pregabalin, reproduced above.
RESPONSE TO ATTORNEY ARGUMENTS:
The Attorney response states claim 1 has been amended to recite wherein the glaucoma is normal tension glaucoma (NTG) and the subject's glaucoma progression is not responsive to intraocular pressure (IOP) lowering; where such patient population is novel.
The Attorney response argues NTG, along with other glaucoma types, shares pathologies of retinal ganglion cell (RGC) and optic (ON) nerve damage (citing the specification). The Attorney response argues that the specification pregabalin is unexpectedly capable of treating glaucoma by providing neuroprotective effects to control glaucoma progression in a manner distinct from glaucoma treatment resulting from IOP lowering, referencing Examples 2 and 4 and the in vivo BXD29 mouse model, demonstrating no IOP lowering in the mouse model, i.e. neuroprotective effects of pregabalin independent of IOP reduction and further mitigating the progression of RGC and ON damage in the BXD29 mice.
In response, it is noted that while Ibrahim and Shields discuss the mechanism of action of gabapentin to lower IOP in glaucoma subjects, it is noted that the approach espoused by Applicant regarding a non-IOP approach to treat is known in the art. As detailed above, “treatment of NTG will target both IOP and IOP-independent risk factors,” (page 533, column 2: Conclusion) where it is suggested to the PHOSITA, that there “[f]uture research is still needed [thus motivating the PHOSITA] to develop clinically effective and useful IOP-independent neuroprotective agents for NTG.” In fact, Song and Caprioli teach the use of a IOP reducing glaucoma drug, the alpha agonist brimonidine, which has “been shown to be neuroprotective [an IOP-independent mechanism of action] in animal models of optic nerve and retinal injury.” See page 532, column 1, first paragraph. Similarly, a PHOSITA, as per Ibrahim and Shields, as evidenced by Song and Caprioli, to look towards IOP lowering drugs in the context of treating NTG not responsive to IOP lowering, where Song and Caprioli teach and suggest such an approach to treat NTG with an IOP-lowering drug, as a research approach to examine a drug’s potential neuroprotective effects in NTG patients not responsive to IOP lowering.
The Attorney response states Ibrahim does not disclose NTG as claimed, and Shields states “control of IOP remains the mainstay of managing NTG patients.” The Attorney response concludes the prima facie case fails, as the Attorney response argues as cited art fails to teach amended claim 1.
As detailed above, Song and Caprioli demonstrate the motivation and suggestion to a PHOSITA to look towards IOP lowering drugs for their potential neuroprotective effects, independent of IOP lowering activity to treat NTG patients, who otherwise would be non-responsive to IOP lowering.
While teaching IOP control is noted with the treatment of NTG, Shields teaches “[t]here is considerable overlap between the two conditions [NTG and POAG] . . . “, where as noted before, other non-IOP factors are involved. See abstract. In support of this teaching of Shields, as evidenced by Song and Caprioli, where the NTG patient is not responsive to the lowering of IOP, Song and Caprioli teach strategies to treat NTG, whether such a patient would be responsive to IOP lowering or not. Along the lines of Shields, Song and Caprioli teach glaucoma can occur at statistically normal IOPs (i.e. NTG patient), i.e., where the claimed subject who a PHOSITA who would determine would not be responsive to IOP lowering. See Abstract. Song and Caprioli suggest that NTG is likely part of continuum of with POAG due to the clinical overlap. See Abstract.
In particular, with regard to the treatment of NTG, where the patient is not responsive to the lowering of IOP, it is noted that Song and Caprioli, recognizes that while NTG patients are those with statistically normal IOPs, it is clear that IOP modification is currently the best established target for treatment. See page 533, column 2, Conclusion. Ideally, future treatment of NTG will target both IOP and IOP-independent risk factors. Id. The teaching of use both IOP dependent and IOP-independent risk factors will teach and suggest the treatment of the claimed patient population who is not responsive to IOP lowering.
Song and Caprioli teach “[f]uture research is still needed [thus motivating the PHOSITA] to develop clinically effective and useful IOP-independent neuroprotective agents for NTG.” In fact, Song and Caprioli teach the use of a IOP reducing glaucoma drug, the alpha agonist brimonidine, which has “been shown to be neuroprotective [an IOP-independent mechanism of action] in animal models of optic nerve and retinal injury.” See page 532, column 1, first paragraph. Similarly, a PHOSITA, as evidenced by Song and Caprioli, to look towards IOP lowering drugs in the context of treating NTG not responsive to IOP lowering, where Song and Caprioli teach and suggest such an approach to treat NTG with an IOP-lowering drug, as a research approach to examine a drug’s potential neuroprotective effects in NTG patients not responsive to IOP lowering.
At the time the present application was filed, it would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) following the teachings of Ibrahim to have incorporated the teachings of Shields, as evidenced by Song & Caprioli, in order to treat normal tension glaucoma, as instantly claimed. A PHOSITA would have had a reasonable expectation of success in doing so based on the prior art teaching of treating POAG and NTG by control of intraocular eye pressure as an underlying premise (Ibrahim and Shields), combined with the known method of treating POAG with pregabalin per Ibrahim.
A PHOSITA would treat not only POAG but also NTG patients not responsive to IOP lowering, where such treatment is suggested by Shields & Caprioli, noting approaches to treat NTG with IOP lowering drugs via a non-IOP-lowering mechanism of action, i.e. neuroprotection.
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, 9, 11, 14-15, 17-21, 23, and 30-34 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-39 of U.S. Patent No. U.S. 11,826,467 B2 (cited on the PTO-892 form mailed 8/26/2024) in view of Shields, Current Opinion in Ophthalmology 2008, 19:85–88 2008, as evidenced by Song BJ and Caprioli J. New directions in the treatment of normal tension glaucoma. Indian J Ophthalmol 2014;62:529-37.
Regarding the rejected claims, the reference patent discloses a microemulsion comprising: (a) a discontinuous internal phase comprising an aqueous solution encompassed within an internal emulsifier, wherein the aqueous solution comprises pregabalin; (b) a continuous oil phase encompassing the internal phase; (c) an external emulsifier encompassing the oil phase; and (d) an aqueous phase surrounding the external emulsifier and comprising a hydrogel comprising a mucoadhesive polymer, wherein the microemulsion is a water-in-oil-in-water microemulsion (W/O/W ME) and comprises globules formed by (a)-(c) that are between about 1 nm and about 50 nm in diameter, see claim 1.
The reference patent claims an internal emulsifier comprises a surfactant with HLB of 3-7; aqueous solution/phase (deionized water, saline, phosphate buffered saline, artificial tears, or balanced salt solution); oil phase as claimed, HLB 10-16; external phase HLB value of 10-16; a mucoadhesive polymer ( polyacrylic acid, alginic acid or a salt thereof, chitosan, dextran, pectin, gelatin, polyvinylpyrrolidone, N-methylpyrrolidone, hyaluronic acid or a salt thereof, gellan gum, xanthan gum, agar, glycocholic acid or a salt thereof, carbomer, or a derivative of any of the foregoing, or a combination thereof); as a topical formulation. See claims.
The reference patent discloses a method for treating glaucoma in a subject in need thereof, comprising administering to the subject an effective amount of the microemulsion of claim 1, wherein administering the microemulsion reduces the intraocular pressure of the subject, see claim 21.
The reference patent further limits the method of claim 21 and claims administration of the W/O/W ME to one or both eyes, via eye drops, once a day; an internal emulsifier comprises a surfactant with HLB of 3-7; aqueous solution/phase (deionized water, saline, phosphate buffered saline, artificial tears, or balanced salt solution); oil phase as claimed, HLB 10-16; external phase HLB value of 10-16; a mucoadhesive polymer (polyacrylic acid, alginic acid or a salt thereof, chitosan, dextran, pectin, gelatin, polyvinylpyrrolidone, N-methylpyrrolidone, hyaluronic acid or a salt thereof, gellan gum, xanthan gum, agar, glycocholic acid or a salt thereof, carbomer, or a derivative of any of the foregoing, or a combination thereof); as a topical formulation, see claim 22-39 that further the method of claim 21.
Shields discloses that NTG and primary open angle glaucoma (POAG) represent a continuum of open-angle glaucoma, in which a certain level of intraocular pressure (IOP) is the predominant causative risk factor in POAG, see abstract.
While teaching IOP control is noted with the treatment of NTG, Shields teaches “[t]here is considerable overlap between the two conditions [NTG and POAG] . . . “, where as noted before, other non-IOP factors are involved. See abstract.
In support of this teaching of Shields, as evidenced by Song and Caprioli, where the NTG patient is not responsive to the lowering of IOP, Song and Caprioli teach strategies to treat NTG, whether such a patient would be responsive to IOP lowering or not. Along the lines of Shields, Song and Caprioli teach glaucoma can occur at statistically normal IOPs (i.e. NTG patient), i.e., where the claimed subject who a PHOSITA who would determine would not be responsive to IOP lowering. See Abstract. Song and Caprioli suggest that NTG is likely part of continuum of with POAG due to the clinical overlap. See Abstract.
In particular, with regard to the treatment of NTG, where the patient is not responsive to the lowering of IOP, it is noted that Song and Caprioli, recognizes that while NTG patients are those with statistically normal IOPs, it is clear that IOP modification is currently the best established target for treatment. See page 533, column 2, Conclusion. Ideally, future treatment of NTG will target both IOP and IOP-independent risk factors. Id. The teaching of use both IOP dependent and IOP-independent risk factors will teach and suggest the treatment of the claimed patient population who is not responsive to IOP lowering.
Song and Caprioli teach “[f]uture research is still needed [thus motivating the PHOSITA] to develop clinically effective and useful IOP-independent neuroprotective agents for NTG.” In fact, Song and Caprioli teach the use of a IOP reducing glaucoma drug, the alpha agonist brimonidine, which has “been shown to be neuroprotective [an IOP-independent mechanism of action] in animal models of optic nerve and retinal injury.” See page 532, column 1, first paragraph. Similarly, a PHOSITA, as per the reference patent and Shields, as evidenced by Song and Caprioli, to look towards IOP lowering drugs in the context of treating NTG not responsive to IOP lowering, where Song and Caprioli teach and suggest such an approach to treat NTG with an IOP-lowering drug, as a research approach to examine a drug’s potential neuroprotective effects in NTG patients not responsive to IOP lowering.
At the time the present application was filed, it would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) following the teachings of the reference patent to have incorporated the teachings of Shields, as evidenced by Shields & Caprioli, in order to treat normal tension glaucoma, as instantly claimed. A PHOSITA would have had a reasonable expectation of success in doing so based on the prior art teaching of treating POAG and NTG by control of intraocular eye pressure as an underlying premise (reference patent and Shields), combined with the known method of treating POAG with pregabalin per the reference patent. A PHOSITA would treat not only POAG but also NTG patients not responsive to IOP lowering, where such treatment is suggested by Song & Caprioli, noting approaches to treat NTG with IOP lowering drugs via a non-IOP-lowering mechanism of action, i.e. neuroprotection.
Claims 1, 11 and 14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 30-31, 33-36, and 66-76 of copending Application No. 18489682 in view of Shields, Current Opinion in Ophthalmology 2008, 19:85–88 2008 as evidenced by Song BJ and Caprioli J. New directions in the treatment of normal tension glaucoma. Indian J Ophthalmol 2014;62:529-37. This is a provisional nonstatutory double patenting rejection.
The examined claims are directed to a method treating NTG in a subject in need with a pharmaceutical composition comprising pregabalin, administered once a day.
Application 18489682 is directed to claim 30, a method for treating glaucoma in a subject in need thereof, comprising administering to the subject an amount effective amount of an inhibitor of Calcium Voltage-Gated Channel Auxiliary Subunit Alpha2delta 1 (CACNA2d1) protein, i.e. POAG per claim 31. As per claims 33-36 and 66-76, the inhibitor is pregabalin (or a pharmaceutically acceptable salt), topically administered via eye drops.
While the reference application claims treatment of primary open angle glaucoma (POAG), it does not claim normal tension glaucoma (NTG) as claimed. However, one of ordinary skill in the art would have a reasonable expectation of success in arriving at the claimed invention because normal tension glaucoma is a common form of glaucoma (i.e., open angle), including primary open angle glaucoma, see Shields 2008 abstract.
Shields discloses that NTG and POAG represent a continuum of open-angle glaucoma, in which a certain level of intraocular pressure (IOP) is the predominant causative risk factor in POAG, see abstract. Based on this teaching, one of ordinary skill in the art would have a reasonable expectation of success to treat not only POAG as per the reference application, but also NTG based on the teachings of Shields.
Shields discloses that NTG and primary open angle glaucoma (POAG) represent a continuum of open-angle glaucoma, in which a certain level of intraocular pressure (IOP) is the predominant causative risk factor in POAG, see abstract.
While teaching IOP control is noted with the treatment of NTG, Shields teaches “[t]here is considerable overlap between the two conditions [NTG and POAG] . . . “, where as noted before, other non-IOP factors are involved. See abstract.
In support of this teaching of Shields, as evidenced by Song and Caprioli, where the NTG patient is not responsive to the lowering of IOP, Song and Caprioli teach strategies to treat NTG, whether such a patient would be responsive to IOP lowering or not. Along the lines of Shields, Song and Caprioli teach glaucoma can occur at statistically normal IOPs (i.e. NTG patient), i.e., where the claimed subject who a PHOSITA who would determine would not be responsive to IOP lowering. See Abstract. Song and Caprioli suggest that NTG is likely part of continuum of with POAG due to the clinical overlap. See Abstract.
In particular, with regard to the treatment of NTG, where the patient is not responsive to the lowering of IOP, it is noted that Song and Caprioli, recognizes that while NTG patients are those with statistically normal IOPs, it is clear that IOP modification is currently the best established target for treatment. See page 533, column 2, Conclusion. Ideally, future treatment of NTG will target both IOP and IOP-independent risk factors. Id. The teaching of use both IOP dependent and IOP-independent risk factors will teach and suggest the treatment of the claimed patient population who is not responsive to IOP lowering.
Song and Caprioli teach “[f]uture research is still needed [thus motivating the PHOSITA] to develop clinically effective and useful IOP-independent neuroprotective agents for NTG.” In fact, Song and Caprioli teach the use of a IOP reducing glaucoma drug, the alpha agonist brimonidine, which has “been shown to be neuroprotective [an IOP-independent mechanism of action] in animal models of optic nerve and retinal injury.” See page 532, column 1, first paragraph. Similarly, a PHOSITA, as per the reference patent and Shields, as evidenced by Song and Caprioli, to look towards IOP lowering drugs in the context of treating NTG not responsive to IOP lowering, where Song and Caprioli teach and suggest such an approach to treat NTG with an IOP-lowering drug, as a research approach to examine a drug’s potential neuroprotective effects in NTG patients not responsive to IOP lowering.
At the time the present application was filed, it would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) following the teachings of the reference patent to have incorporated the teachings of Shields, as evidenced by Shields & Caprioli, in order to treat normal tension glaucoma, as instantly claimed. A PHOSITA would have had a reasonable expectation of success in doing so based on the prior art teaching of treating POAG and NTG by control of intraocular eye pressure as an underlying premise (reference patent and Shields), combined with the known method of treating POAG with pregabalin per the reference patent. A PHOSITA would treat not only POAG but also NTG patients not responsive to IOP lowering, where such treatment is suggested by Song & Caprioli, noting approaches to treat NTG with IOP lowering drugs via a non-IOP-lowering mechanism of action, i.e. neuroprotection.
Claims 1, 11 and 14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 30-31, 33-36, and 66-76 of copending Application No. 18/920,652 in view of Shields, Current Opinion in Ophthalmology 2008, 19:85–88 2008 as evidenced by Song BJ and Caprioli J. New directions in the treatment of normal tension glaucoma. Indian J Ophthalmol 2014;62:529-37. This is a provisional nonstatutory double patenting rejection.
The examined claims are directed to a method treating NTG in a subject in need with a pharmaceutical composition comprising pregabalin, administered once a day.
Application 18/920,652 is directed to claim a method for treating glaucoma in a subject in need thereof, comprising administering to the subject an effective amount of a composition comprising an inhibitor of Calcium Voltage-Gated Channel Auxiliary Subunit Alpha2delta 1 (CACNA2d1) protein and a mucoadhesive polymer, i.e. POAG per claim 31. As per claims 33-36 and 66-76, the inhibitor is pregabalin (or a pharmaceutically acceptable salt), topically administered via eye drops.
While the reference application claims treatment of primary open angle glaucoma (POAG), it does not claim normal tension glaucoma (NTG) as claimed. However, one of ordinary skill in the art would have a reasonable expectation of success in arriving at the claimed invention because normal tension glaucoma is a common form of glaucoma (i.e., open angle), including primary open angle glaucoma, see Shields 2008 abstract.
Shields discloses that NTG and POAG represent a continuum of open-angle glaucoma, in which a certain level of intraocular pressure (IOP) is the predominant causative risk factor in POAG, see abstract. Based on this teaching, one of ordinary skill in the art would have a reasonable expectation of success to treat not only POAG as per the reference application, but also NTG based on the teachings of Shields.
Shields discloses that NTG and primary open angle glaucoma (POAG) represent a continuum of open-angle glaucoma, in which a certain level of intraocular pressure (IOP) is the predominant causative risk factor in POAG, see abstract.
While teaching IOP control is noted with the treatment of NTG, Shields teaches “[t]here is considerable overlap between the two conditions [NTG and POAG] . . . “, where as noted before, other non-IOP factors are involved. See abstract.
In support of this teaching of Shields, as evidenced by Song and Caprioli, where the NTG patient is not responsive to the lowering of IOP, Song and Caprioli teach strategies to treat NTG, whether such a patient would be responsive to IOP lowering or not. Along the lines of Shields, Song and Caprioli teach glaucoma can occur at statistically normal IOPs (i.e. NTG patient), i.e., where the claimed subject who a PHOSITA who would determine would not be responsive to IOP lowering. See Abstract. Song and Caprioli suggest that NTG is likely part of continuum of with POAG due to the clinical overlap. See Abstract.
In particular, with regard to the treatment of NTG, where the patient is not responsive to the lowering of IOP, it is noted that Song and Caprioli, recognizes that while NTG patients are those with statistically normal IOPs, it is clear that IOP modification is currently the best established target for treatment. See page 533, column 2, Conclusion. Ideally, future treatment of NTG will target both IOP and IOP-independent risk factors. Id. The teaching of use both IOP dependent and IOP-independent risk factors will teach and suggest the treatment of the claimed patient population who is not responsive to IOP lowering.
Song and Caprioli teach “[f]uture research is still needed [thus motivating the PHOSITA] to develop clinically effective and useful IOP-independent neuroprotective agents for NTG.” In fact, Song and Caprioli teach the use of a IOP reducing glaucoma drug, the alpha agonist brimonidine, which has “been shown to be neuroprotective [an IOP-independent mechanism of action] in animal models of optic nerve and retinal injury.” See page 532, column 1, first paragraph. Similarly, a PHOSITA, as per the reference application and Shields, as evidenced by Song and Caprioli, to look towards IOP lowering drugs in the context of treating NTG not responsive to IOP lowering, where Song and Caprioli teach and suggest such an approach to treat NTG with an IOP-lowering drug, as a research approach to examine a drug’s potential neuroprotective effects in NTG patients not responsive to IOP lowering.
At the time the present application was filed, it would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) following the teachings of the reference application to have incorporated the teachings of Shields, as evidenced by Shields & Caprioli, in order to treat normal tension glaucoma, as instantly claimed. A PHOSITA would have had a reasonable expectation of success in doing so based on the prior art teaching of treating POAG and NTG by control of intraocular eye pressure as an underlying premise (reference patent and Shields), combined with the known method of treating POAG with pregabalin per the reference application. A PHOSITA would treat not only POAG but also NTG patients not responsive to IOP lowering, where such treatment is suggested by Song & Caprioli, noting approaches to treat NTG with IOP lowering drugs via a non-IOP-lowering mechanism of action, i.e. neuroprotection.
RESPONSE TO ATTORNEY ARGUMENTS:
The Attorney response traverses the three ODP rejections (over the ‘467 patent, Application 18489682 and Application 118920652 all in view of Shields) as the references are substantively the same to each other and Ibrahim, as detailed above for the 103 rejection.
The Attorney response similarly argues the traversal of the rejection for obviousness over Ibrahim in view of Shields is substantively the same as its traversal of the ODP rejections. Shields and the above-three double patenting references do not teach or suggest the limitations of amended claim 1, nor do they provide a person of skill with a reasonable expectation of success.
In response, the above rejections are modified to be evidenced by the teachings of Song and Caprioli as detailed above.
As detailed above, Song and Caprioli proves the motivation and suggestion to a PHOSITA to look towards IOP lowering drugs for their potential neuroprotective effects, independent of IOP lowering activity to treat NTG patients, who otherwise would be non-responsive to IOP lowering.
While teaching IOP control is noted with the treatment of NTG, Shields teaches “[t]here is considerable overlap between the two conditions [NTG and POAG] . . . “, where as noted before, other non-IOP factors are involved. See abstract. In support of this teaching of Shields, as evidenced by Song and Caprioli, where the NTG patient is not responsive to the lowering of IOP, Song and Caprioli teach strategies to treat NTG, whether such a patient would be responsive to IOP lowering or not. Along the lines of Shields, Song and Caprioli teach glaucoma can occur at statistically normal IOPs (i.e. NTG patient), i.e., where the claimed subject who a PHOSITA who would determine would not be responsive to IOP lowering. See Abstract. Song and Caprioli suggest that NTG is likely part of continuum of with POAG due to the clinical overlap. See Abstract.
In particular, with regard to the treatment of NTG, where the patient is not responsive to the lowering of IOP, it is noted that Song and Caprioli, recognizes that while NTG patients are those with statistically normal IOPs, it is clear that IOP modification is currently the best established target for treatment. See page 533, column 2, Conclusion. Ideally, future treatment of NTG will target both IOP and IOP-independent risk factors. Id. The teaching of use both IOP dependent and IOP-independent risk factors will teach and suggest the treatment of the claimed patient population who is not responsive to IOP lowering.
Song and Caprioli teach “[f]uture research is still needed [thus motivating the PHOSITA] to develop clinically effective and useful IOP-independent neuroprotective agents for NTG.” In fact, Song and Caprioli teach the use of a IOP reducing glaucoma drug, the alpha agonist brimonidine, which has “been shown to be neuroprotective [an IOP-independent mechanism of action] in animal models of optic nerve and retinal injury.” See page 532, column 1, first paragraph. Similarly, a PHOSITA, as per the reference patent/applications and Shields, as evidenced by Song and Caprioli, to look towards IOP lowering drugs in the context of treating NTG not responsive to IOP lowering, where Song and Caprioli teach and suggest such an approach to treat NTG with an IOP-lowering drug, as a research approach to examine a drug’s potential neuroprotective effects in NTG patients not responsive to IOP lowering.
At the time the present application was filed, it would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) following the teachings of the reference patent/applications to have incorporated the teachings of Shields, as evidenced by Song & Caprioli, in order to treat normal tension glaucoma, as instantly claimed. A PHOSITA would have had a reasonable expectation of success in doing so based on the prior art teaching of treating POAG and NTG by control of intraocular eye pressure as an underlying premise (per the reference patent/applications and Shields), combined with the known method of treating POAG with pregabalin per the reference patent/applications.
Conclusion/Correspondence
In summary, no claims are 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 WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
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, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/WILLIAM Y LEE/
Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 This application is a CON of 18/022,252 filed on 02/20/2023. Application No. 18/022,252 is a 371 of PCT/US2021/047109 filed 08/23/2021. International Application PCT/US2021/047109 has claims priority to 63/068,917 filed 08/21/2020.