DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant's election with traverse of
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in the reply filed on 5/11/26 is acknowledged. The traversal is on the ground(s) that the applied-in-restriction reference Dieckmann et al. does not “”clearly teach” that NGF is known to be administered to treat NCP”, this allegedly supported by a partial citation from that reference on page 2 of Applicant’s Remarks. This is not found persuasive because Dieckmann et al. clearly teaches that administering 20% autologous serum tears (AST), which contains NGF (and other components per the excerpt below) to NCP subjects “have demonstrated significant improvement of symptoms of allodynia and photoallodynia” within 3.6 months of treatment. Allodynia is a form or type of pain, so the AST which comprises NGF treats and reduces pain. Regarding claim 11 in particular, given that Dieckmann et al. teaches administering AST which comprises NGF, and given that the transitional term “comprising” is inclusive or open-ended and does not exclude additional, unrecited elements. See MPEP 2111.03, Dieckmann et al. not only is effective to break unity of invention, it also anticipates claim 11 because the administered AST composition comprises NGF, and when administered as taught in Dieckmann et al. it treats NCP in subjects in need thereof.
A relevant excerpt follows that clearly counters the partial excerpt advanced by applicant on page 2 of its Remarks:
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The requirement is still deemed proper and is therefore made FINAL.
Applicant states that “Claims 11-14 and 19-23 read on the elected species.”
Claims 15-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 5/11/26. The examiner responded to this traversal above.
PLEASE NOTE: The 3/11/26 Restriction/Election requirement included the requirement to elect a “a single distinct and disclosed species … providing the particular nerve growth factor being administered,” page 3. In that applicant only responded by stating rhNGF, the examiner interprets this elected species as being a single species of human NGF, produced by recombinant methods, and not having any modifications from the native sequence, and particularly the FDA approved sequence of applicant marketed as OXERVATE®, this interpretation supported by the specification, paragraph 0003.
Claim Status
Claims 11-23 are pending.
Claims 1-11 are cancelled.
Claims 15-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected species, there being no allowable generic or linking claim.
Claims 11-14 and 19-23 are pending and under examination.
Claims 11-14 and 19-23 are rejected.
Claims 11 and 12 are objected to.
Priority
The instant application, filed 10/09/2023 is a National Stage entry of PCT/US2022/024519 , International Filing Date: 04/13/2022
PCT/US2022/024519 Claims Priority from Provisional Application 63174163 , filed 04/13/2021.
Information Disclosure Statement
The Examiner has considered the reference(s) provided in the 10/9/23 and 4/22/26
Information Disclosure Statements, and provides a signed and dated copy of each herewith.
Claim Objections
Claim 11 is objected to because of the following informalities: in line 2 “Nerve Growth Factor” should appear before “NGF” and “NGF” should then be enclosed in parentheses. Appropriate correction is required.
Claim 12 is objected to because of the following informalities: “recombinant human Nerve Growth Factor” should appear before “rhNGF” and “rhNGF” should then be enclosed in parentheses. . Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 13 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
It is unclear whether any “mild” inflammation anywhere in the subject’s body is what is encompassed by “and/or who has mild inflammation.”
Also, the term “mild” in claim 13 is a relative term which renders the claim indefinite. The term “mild” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. One of ordinary skill in the art would not be able to distinguish, in a subject suffering from neuropathic corneal pain, whether that subject has “mild” or a more severe level of inflammation, nor per immediately above whether such inflammation is in the cornea or elsewhere.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 11, 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dieckmann et al., Ophthalmology, 2017: 124:S34-S47, provided in 10/9/23 IDS).
This rejection extends beyond the elected species of rhNGF for compact prosecution and in view of the traversal arguments against the use of this reference in the Restriction Requirement.
Claim 11 is directed to a method of treating neuropathic corneal pain (NCP) in a subject in need thereof, comprising administration of a composition comprising NGF, this “NGF” interpreted as Nerve Growth Factor.
The transitional term “comprising” is inclusive or open-ended and does not exclude additional, unrecited elements. See MPEP 2111.03.
Dieckmann et al., based at least on stating page 2 that NCP subjects “have demonstrated significant improvement of symptoms of allodynia and photoallodynia” within 3.6 months of treatment, given that allodynia is a form or type of pain, so the AST which comprises NGF treats and reduces pain, clearly meets, by that its administering 20% autologous serum tears (AST), which comprises NGF (and other components), a method of treating neuropathic corneal pain (NCP) in a subject in need thereof, comprising administration of a composition comprising NGF, this “NGF” interpreted as Nerve Growth Factor.
Therefore Dieckmann et al. anticipates claim 11.
Dieckmann et al. also anticipates claims 19 based on its Figs. 2 and 4 and accompanying text of these Figures.1
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 11-14, 19-23 are rejected under 35 U.S.C. 103 as being unpatentable over “What is Neuropathic Pain?” article by Reena Mukama, Am. Acad. of Ophthalmology website, November 2019 (“Mukama”), provided in 4/22/26 IDS, in view of Dieckmann et al., Ophthalmology, 2017: 124:S34-S47, provided in 10/9/23 IDS), Rosano et al., PROTEIN SCIENCE 2019 | VOL 28:1412–1422 (“Rosano”) copy provided, and OXERVATE® Prescribing Label and Information, 2018, 19 pages, copy provided (“Oxer”).
Claim 11 is directed to a method of treating neuropathic corneal pain (NCP) in a subject in need thereof, comprising administration of a composition comprising NGF, this “NGF” interpreted as Nerve Growth Factor.
The elected species of NGF is recombinant human NGF (rhNGF).
The elected species of subject treated has been stated to be “a patient suffering from NCP who responds to treatment with a topical anesthetic.”
Mukama teaches that “Neuropathic corneal pain is a condition that causes your eyes, face or head to be over sensitive. It also causes them pain.” Page 1. Mukama also teaches symptoms and causes of NCP, pages 1 and 2.
Mukama teaches that when dry eye therapies and drops for pain don’t improve symptoms, doctors suspect NCP, page 2.
Among treatments, which aim to regenerate nerves and reduce inflammation that makes nerves more sensitive, are included autologous serum tears (AST) and “topical recombinant corneal nerve growth factor” in a list of seven treatments, are page 2.
The level of ordinary skill in the art is moderately high.
Dieckmann et al. also teaches as a therapeutic strategy for treatment of NCP “Neuroregenerative Therapy”, with AST, which requires purification from the patient’s own blood, and teaches that AST comprises NGF, pages page S36, and specifically focuses on effectiveness of NGF alone, teaching “NGF reduced allodynia and hyperalgesia through reduction of reactive astrocytosis and glial modulation,” Id., see also page S37, and note that Dieckmann et al. also clearly teaches responsiveness to the topical anesthetic proparacaine challenge segregates subjects to those who have complete relief, categorizing these subjects as having peripheral pain, versus mixed versus centralized pain, Figure 2 and associated text, also see Figure 4 and associated text, so identifying “a patient suffering from NCP who responds to treatment with a topical anesthetic” as a candidate for treatment with AST and particularly NGF (for neuroregenerative therapy) if such patient’s response to the topical anesthetic proparacaine challenge indicated peripheral pain, see Figure 4 and accompanying text, but neither Mukama nor Dieckmann et al. explicitly teach that the NGF is recombinant human NGF.
Rosano teaches that protein purification “can be performed from the natural source of the protein; however, this approach is usually cumbersome and inefficient for most of them,” page 1412, and also teaches that making proteins “Using E. coli as a microbial cell factory for producing recombinant proteins lowers the costs of production and improves the yield. Nowadays, many proteins of commercial interest are produced in E. coli,” Id., citations omitted.
Rosano clearly provides a cost-based motivation to obtain and administer a recombinant protein such as NGF rather than subjecting a patient, already in distress over NCP, to additional drawing of blood to obtain AST which comprises NGF.
Oxer teaches a recombinant human NGF that is 118 amino acids long, and that is available in an FDA approved pharmaceutical composition that is used to treat a different ophthalmic condition, neuropathic keratitis, but is approved for applying to the cornea/eyes, including in a concentration of 0.002% (20 mcg/mL), at such dosage at a frequency of one drop of OXERVATE in the affected eye(s), 6 times per day at 2-hour intervals, for eight weeks, pages 1 and 8 of Oxer.
When wanting to administer NGF as a neuroregenerative agent to treat NCP, one of ordinary skill in the art would reasonably consider administering the rhNGF available from Oxer, based on its known and approved use on the same body part, the eyes/cornea which suggests it has passed safety evaluations and can be administered in the same dosage range without detrimental effects, this selection also avoiding the need and expense of drawing blood from the subject/patient to obtain AST. There would have been a reasonable expectation of success given that it is a NGF and both Mukama and Dieckmann et al. teach the role of NGF in treating and/or improving NCP symptoms through its function in neuroregenerative therapy for NCP.
Additionally, given the limited number of possible treatments set forth in Mukama, it would have been obvious to try administering NGF topically to treat NCP. At the time of applicant’s filing, there had been a recognized problem of treating NCP, thus a need in the art, to solve this problem in such patients. Mukama had identified a finite number of identified, predictable potential solutions to this problem of treating NCP, this including administering NGF. One of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success, and given the teachings of Dieckmann et al., when evaluating NGF among those known potential solutions would have had a reasonable expectation of success, particularly for subjects who demonstrated peripheral pain only after the proparacaine challenge test.
Based on any combination of the above bases, claims 11-14 when considering the elected species would have been obvious.
Claim 19 also would have been obvious given the teachings of topical administration to the ocular surface in Mukama, Dieckmann et al., and Oxer.
Claims 20-22 would have been obvious given the dosage of Oxer as a starting point given its known safety based on FDA approval.
Claim 23 would have been obvious given Dieckmann et al. dosing regimen for AST, see page S37 (8 times daily until significant relief/resolution, relief observed within 3 to 4 months), and Oxer regimen “One drop of OXERVATE in the affected eye(s), 6 times per day at 2-hour intervals, for eight weeks”. Please see MPEP 2144.05 re overlap of ranges.
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 11 and 12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 5, and 18-20 of copending Application No. 19099530 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application claim 1’s “for use by topical administration in the treatment of an ocular disorder known to be treatable by NGF” (nerve growth factor) pertaining to its “combination of nerve growth factor (NGF) and sesamin”, and given that reference claims 18-20 include neuropathic corneal pain among “an ocular disorder known to be treatable by NGF”, instant claim 11 would have been obvious. In view of reference claim 5, instant claim 12 also would have been obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 13, 14, 19-23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over 1, 5, and 18-20 of copending Application No. 19099530 (reference application), as applied to claims 11 and 12 above, and further in view of Dieckmann et al., Ophthalmology, 2017: 124:S34-S47, provided in 10/9/23 IDS) and OXERVATE® Prescribing Label and Information, 2018, 19 pages, copy provided (“Oxer”).
Instant claims 11 and 12 are rejected as set forth above.
Reference application claims do not pertain to responsiveness to topical anesthetic nor dosing concentrations or regimen over time.
The level of ordinary skill in the art is moderately high.
Dieckmann et al. teaches responsiveness to the topical anesthetic proparacaine challenge segregates subjects to those who have complete relief, categorizing these subjects as having peripheral pain, versus mixed versus centralized pain, Figure 2 and associated text, also see Figure 4 and associated text, so identifying “a patient suffering from NCP who responds to treatment with a topical anesthetic” as a candidate for treatment with AST and particularly NGF (for neuroregenerative therapy) if such patient’s response to the topical anesthetic proparacaine challenge indicated peripheral pain, see Figure 4 and accompanying text.
Applying such teachings in view of reference application claims 1, 5, and 18-20 instant claims 13 and 14 would have been obvious.
Relative to instant claims 20-23, while Dieckmann et al. teaches some administering regimen, it does not teach extensive concentration administering of NGF.
Oxer teaches a recombinant human NGF that is 118 amino acids long, and that is available in an FDA approved pharmaceutical composition that is used to treat a different ophthalmic condition, neuropathic keratitis, but is approved for applying to the cornea/eyes, including in a concentration of 0.002% (20 mcg/mL), at such dosage at a frequency of one drop of OXERVATE in the affected eye(s), 6 times per day at 2-hour intervals, for eight weeks, pages 1 and 8 of Oxer.
Claim 19 would have been obvious given the teachings of topical administration to the ocular surface in Oxer.
Claims 20-22 would have been obvious given the dosage of Oxer as a starting point given its known safety based on FDA approval.
Claim 23 would have been obvious given Dieckmann et al. dosing regimen for AST (which comprises NGF), see page S37 (8 times daily until significant relief/resolution, relief observed within 3 to 4 months), and Oxer regimen “One drop of OXERVATE in the affected eye(s), 6 times per day at 2-hour intervals, for eight weeks”. Please see MPEP 2144.05 re overlap of ranges.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH FISCHER whose telephone number is (571)270-7925, and whose direct facsimile number is (571)270-8925. The examiner can normally be reached on Monday to Friday, 9:00 AM to 5:00 PM, however noting that the examiner will not normally be working on Monday/Tuesday and on Wednesday-Friday on alternating weeks, but will promptly answer messages upon his return to work.
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/JOSEPH FISCHER/Primary Examiner, Art Unit 1658
1 Notwithstanding that applicant states that only claims 11-14 and 19-23 read on the elected species (resulting in the withdrawal of claims 15-18 above), it is the examiner’s view that Dieckmann et al., by itself as well as when combined with references in the 35 USC 103 rejection, would render obvious claims 17 and 18 in view of its teachings.
Prosecution Insights