Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on September 22, 2025 has been entered.
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
3. Applicant’s amendment filed September 22, 2025 is acknowledged. Claims 1-15 and 17-30 are canceled. Claims 16, 31-32, 37-42 are amended. Claims 43-48 are newly added. Claims 16 and 31-42 and new claims 43-48 are pending in this application and under examination in this office action.
4. Applicant’s arguments filed on September 22, 2025 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
Claim Rejections/Objections Withdrawn
5. The rejection of claim 31 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in response to Applicant’s amendment to the claim.
Claim Rejections/Objections Maintained
In view of the amendment filed on September 22, 2025, the following rejections are maintained.
Claim Rejections - 35 USC § 112
6. 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.
Claims 32-40 and 46-48 are 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 pre-AIA the applicant regards as the invention. The rejection is maintained for the reasons of record and the reasons set forth below.
Response to Arguments
On p. 4 of the response, Applicant argues that the rejection has been overcome in view of amendment to claim 16 by specifying that the compositions are ophthalmic aqueous liquid compositions.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant' s arguments, the examiner asserts that based on MPEP§2171-MPEP§2173, Claims 32-40 and 46-48 are indefinite because:
i. Claim 32 recites the limitation “the pharmaceutical composition” and the limitation “said pharmaceutical composition”. It is unclear whether the limitation “the pharmaceutical composition” and the limitation “said pharmaceutical composition” refer to the same pharmaceutical composition. Thus, the claim is indefinite.
ii. claims 37-39 recite the limitation “said ophthalmic aqueous composition” and the limitation “the ophthalmic aqueous composition”. It is unclear whether the limitation “said ophthalmic aqueous composition” and the limitation “the ophthalmic aqueous composition” refer to the same ophthalmic aqueous composition. Thus, the claims are indefinite.
iii. The rest of claims are indefinite as depending from an indefinite claim.
Accordingly, the rejection of claims 32-40 and 46-48 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is maintained.
Claim Rejections - 35 USC § 102
7. Claims 16 and 31-48 are rejected under 35 U.S.C. 102(a)(1) & (a)(2) as being anticipated by Lambiase (US9468665) as evidenced by Zhu et al. (US2023/0037311, published Feb 9, 2023, priority Dec 20, 2019; also issued as US12351612) and the factsheet of rh-bNGF (retrieved from the website: immunotools.de/html/cytokines/ngfb.pdf on 09/29/2026). The references of Presta and Eng are withdrawn in response to Applicant’s amendment to the claims. The references of Zhu et al. (US2023/0037311) and factsheet of rhNGF/rh b-NGF are necessitated by Applicant’s amendment to the claims. The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 16 and 31-48 as amended are drawn to a method for treating glaucoma in a subject, the method comprising administering NGF consisting of the sequence of SEQ ID NO:1 (118aa) to an eye of the subject, wherein the method does not comprise administration of NGF consisting of the sequence of SEQ ID NO:2 (120aa) or 4 (119aa).
Briefly, Lambiase (US946866) teaches a method for treating glaucoma in a human patient in need thereof, comprising topically administering to an ocular surface of the human patient an ophthalmic preparation comprising 10pg/ml to 500pg/ml or 1-1000ug/ml of NGF (see col.5, lines 62-67, claims 1-6) including human NGF (hNGF) or human recombinant NGF (rhNGF) (see abstract; col. 9-col.13, table 5; claims 1-6), wherein the ophthalmic preparation comprises hNGF or rhNGF in a pharmaceutically acceptable carrier in a form of solution including an ophthalmic solution (col.5, lines 62-col. 6, line 60; claims 1-6), wherein the hNGF or rhNGF is bNGF which is a dimer of 13KD constituted by two identical chains of 118 amino acids (see col. 2, lines 9-10; the sequence alignment; abstract; col. 9-col.13, table 5; claims 1-6), which meets the limitations recited in claims 16 and 31-48. The hNGF or rhNGF in the ophthalmic preparation disclosed by Lambiase comprises only 118 amino acid residues and consists of the amino acid sequence of instant SEQ ID NO:1 as evidenced by Zhu et al. (US2023/0037311) (see the sequence alignment below; para. [0014]; [0032]; claims 2 and 11) and thus, meets the limitations recited in claims 16, 37-39, 41, 43-48. The rhNGF in the ophthalmic preparation disclosed by Lambiase consists of SEQ ID NO:1 (118 aa) and does not contain any post-translational modification as in claim 31 as also evidenced by the factsheet of rh beta-NGF (from the website: immunotools.de/html/cytokines/ngfb.pdf). The hNGF or rhNGF in the ophthalmic preparation disclosed by Lambiase comprises at least one pharmaceutically acceptable excipient in claim 32 (see col. 5, line 62 to col. 6, line 60) and for ophthalmic use, a liquid ophthalmic composition, an ophthalmic aqueous liquid composition recited in claims 33-34 (see col. 5, line 62 to col. 6, line 60). Lambiase teaches administering topically to the anterior segment of the eye in claim 36, posterior segment of the eye in claim 40, intravitreal injection in claims 41-42 (see col. 9, lines 29-38; col. 4, lines 5-9; col. 7, lines 26-30). Lambiase teaches NGF is at a concentration of 1-1000ug/ml of NGF, which is equal to 0.0001%-0.1% and thus is within or overlapping with the claimed range of “ranging from about 0.0001~0.5% w/v of the aqueous composition” recited in claim 37 or “0.001%-0.1% w/v” in claim 38 or “0.002% w/v” recited in claim 39 (see col. 5, line 62 to col. 6, line 7; col.6, lines 55-60). Thus, claims 16 and 31-48 are anticipated by Lambiase (US9468665) as evidenced by Zhu (US2023/0037311) and the factsheet of rh-bNGF.
US20230037311 teaches a recombinant human NGF consisting of the amino acid sequence of SEQ ID NO:1, which is 100% identical to instant SEQ ID NO:1 (see the sequence alignment below).
SEQ ID NO:1
Sequence 1, US/17787558
Publication No. US20230037311A1
GENERAL INFORMATION
APPLICANT: SUNSHINE GUOJIAN PHARMACEUTICAL (SHANGHAI) CO., LTD.
TITLE OF INVENTION: METHOD FOR PREPARING RECOMBINANT HUMAN NERVE GROWTH FACTOR
FILE REFERENCE: 1238.149427
CURRENT APPLICATION NUMBER: US/17/787,558
CURRENT FILING DATE: 2022-06-20
PRIOR APPLICATION NUMBER: PCT/CN2020/126147
PRIOR FILING DATE: 2020-11-03
PRIOR APPLICATION NUMBER: 201911325340.0
PRIOR FILING DATE: 2019-12-20
NUMBER OF SEQ ID NOS: 2
SEQ ID NO 1
LENGTH: 118
TYPE: PRT
ORGANISM: Homo
Query Match 100.0%; Score 642; Length 118;
Best Local Similarity 100.0%;
Matches 118; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRD 60
Qy 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVR 118
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVR 118
US12351612 teaches a recombinant human NGF consisting of the amino acid sequence of SEQ ID NO:1, which is 100% identical to instant SEQ ID NO:1 (see the sequence alignment below).
SEQ ID NO:1
Sequence 1, US/17787558
Patent No. 12351612
GENERAL INFORMATION
APPLICANT: SUNSHINE GUOJIAN PHARMACEUTICAL (SHANGHAI) CO., LTD.
TITLE OF INVENTION: METHOD FOR PREPARING RECOMBINANT HUMAN NERVE GROWTH FACTOR
FILE REFERENCE: 1238.149427
CURRENT APPLICATION NUMBER: US/17/787,558
CURRENT FILING DATE: 2022-06-20
PRIOR APPLICATION NUMBER: PCT/CN2020/126147
PRIOR FILING DATE: 2020-11-03
PRIOR APPLICATION NUMBER: 201911325340.0
PRIOR FILING DATE: 2019-12-20
NUMBER OF SEQ ID NOS: 2
SEQ ID NO 1
LENGTH: 118
TYPE: PRT
ORGANISM: Homo
Query Match 100.0%; Score 642; Length 118;
Best Local Similarity 100.0%;
Matches 118; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRD 60
Qy 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVR 118
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVR 118
Response to Arguments
On p. 4-5 of the response, Applicant argues that i) Lambiase does not teach a human 118-amino acid NGF sequence of SEQ ID NO:1 because Lambiase only mentioned murine NGF (see col.1, line 58-col.2, line 10); ii) The NGF composition of Lambiase comprises a mixture of NGF isoforms.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2131-2131.01, Lambiase (US946866) and evidentiary references do teach the claimed method because:
i. Lambiase teaches a method of treating glaucoma using the same material: i.e. an ophthalmic preparation comprising 10pg/ml to 500pg/ml or 1-1000ug/ml of hNGF or rhNGF (see claims 4-5; col. 2, lines 9-10) and the same active step: i.e. topically administering to an ocular surface, which is administering to an eye (see claim 1; abstract; col.1, lines 1-12; col.4, lines 5-9; col. 9,lines 28-38) in the same patient population:i.e. a human patient with glaucoma (see claim 1; col. 12, lines 10-14, table 5).
ii. Lambiase does teach the claimed NGF consisting of the sequence of instant SEQ ID NO:1 (118 aa) because the hNGF or rhNGF in the ophthalmic preparation disclosed by Lambiase is bNGF and is a dimer of 13KD constituted by two identical chains of 118 amino acids (see col. 2, lines 9-10; the sequence alignment; abstract; col. 9-col.13, table 5; claims 1-6), and the bNGF-118aa consists of the amino acid sequence of SEQ ID NO:1 as evidenced by Zhu et al. (US2023/0037311) and the factsheet of rhNGF/rh-bNGF. Thus, the hNGF or rhNGF in the ophthalmic preparation disclosed by Lambiase meets the limitations recited in claims 16, 31, 37-39, 41, 43-48.
The hNGF or rhNGF in the ophthalmic preparation disclosed by Lambiase also comprises at least one pharmaceutically acceptable excipient as in claim 32 (see col. 5, line 62 to col. 6, line 60) and for ophthalmic use, a liquid ophthalmic composition, an ophthalmic aqueous liquid composition” in claims 33-34 (see col. 5, line 62 to col. 6, line 60). Lambiase teaches administering topically to the anterior segment of the eye as in claim 36, posterior segment of the eye as in claim 40, intravitreal injection as in claims 41-42 (see col. 9, lines 29-38; col. 4, lines 5-9; col. 7, lines 26-30). Lambiase teaches hNGF or rhNGF is at a concentration of 1-1000ug/ml of NGF, which is equal to 0.0001%-0.1% and thus is within or overlapping with the claimed range of “ranging from about 0.0001~0.5% w/v of the aqueous composition” in claim 37, “0.001%-0.1% w/v” in claim 38 or “0.002% w/v” in claim 39 (see col. 5, line 62 to col. 6, line 7; col.6, lines 55-60). Thus, claims 16 and 31-42 are anticipated by Lambiase (US9468665) as evidenced by Zhu et al. (US2023/0037311) and the factsheet of rhNGF/rh-bNGF.
Accordingly, the rejection of claims 16 and 31-48 under 35 U.S.C. 102(a)(1) & (a)(2) as being anticipated by Lambiase as evidenced by Zhu and the factsheet of rh-bNGF is maintained.
Claim Rejections - 35 USC § 103
8. Claims 16 and 31-48 are rejected under 35 U.S.C. 103 as being unpatentable over Lambiase (US9468665) in view of Zhu et al. (US2023/0037311) and the factsheet of rhNGF/rh-bNGF. The references of Presta et al. (US6333310) and Eng et al. (1997) are withdrawn in response to Applicant’s amendment to the claims. The Zhu (US2023/0037311) and the factsheet of rhNGF/rh-bNGF are necessitated by Applicant’s amendment to the claims. The rejection is maintained for the reasons of record and the reasons set forth below.
Response to Arguments
On p.5-8 of the response, Applicant argues that i) Lambiase does not teach human NGF protein consisting of 118 amino acids because Lambiase teaches murine in experimental section, and cites col.7, lines 6-8, line 46; col.8, line 61 in support of the arguments. Lambiase teaches human NGF has a very low activity and thus does not provide motivation to use human NGF for treatment of glaucoma and cites col. 2, lines 37-40 in support of the arguments; ii) Presta is directed to NGF variants and dose not teach use the NGF consisting of instant SEQ ID NO:1.; iii) Whild Eng teaches that the primary form of NGF produced in cultures is the 118 aa isoform, the generation of the smaller NGF such as 118 or 119 aa is by enzymatic digestion of the 120 aa species; iv) different NGF isoforms are not interchangeable and cites the Section 2.1 of Dr. Andrea Aramini’s declaration, Examples 2-7 of the instant specification and Agarwal et al. (Exp. Opin. Ther. Targ. 2021; 25:585-596), Verbin (Prog. Brain Res. 2015; 230:37-57) and Shi et al. (Develop. Neurobiol. 2007; 67:884-894) in support of the arguments.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2141, MPEP2141-I, rationales identified by the Court in KSR (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, 82 USPQ2d 1385 (2007)), MPEP2141-II, the basic factual inquires of Graham v. John Deere Co.(Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966)),and MPEP §2141.01-2147.03, the cited references do render the claimed invention obvious because:
i. For the reasons set forth above, Lambiase and evidentiary references: Zhu et al. (US2023/0037311) and the factsheet of rhNGF/rh-bNGF do teach the use of NGF consisting of the instant SEQ ID NO:1 for treatment of glaucoma and the claimed method recited in claims 16 and 31-48.
ii. Lambiase does teach the use of rhNGF/rh-bNGF (see claims 4-5; col. 2, lines 9-10) for treating glaucoma. Lambiase teach a method of treating glaucoma using the same material: i.e. an ophthalmic preparation comprising 10pg/ml to 500pg/ml or 1-1000ug/ml of hNGF or rhNGF (see claims 4-5; col. 2, lines 9-10) and the same active step: i.e. topically administering to an ocular surface, which is administering to an eye (see claim 1; abstract; col.1, lines 1-12; col.4, lines 5-9; col. 9,lines 28-38) in the same patient population: i.e. a human patient with glaucoma (see claim 1; col. 12, lines 10-14, table 5). The hNGF or rhNGF consisting of the sequence of instant SEQ ID NO:1 is evidenced by Zhu et al. (US2023/0037311) and the factsheet of rhNGF/rh-bNGF.
iii. Even if Lambiase does not explicitly teach the sequence of hNGF or rhNGF in the ophthalmic preparation used in the Lambiase’s method consists of the sequence of instant SEQ ID NO:1, Zhu (US2023/0037311) and the factsheet of rhNGF/rh-bNGF teach these limitations and provide motivation and an expectation of success in using NGF consisting of the sequence of instant SEQ ID NO:1 because Zhu teaches that rhNGF/rh-bNGF consists of the sequence of instant SEQ ID NO:1 (see the sequence alignment below; para. [0014]; [0032]; claims 2 and 11) and the factsheet of rhNGF/rh-bNGF teaches that rhNGF consists of 118 amino acids (see p.1).
A person of ordinary skill in the art would have recognized that selecting and applying the known hNGF or rhNGF consisting of the known sequences of SEQ ID NO: 1 obtained by the known genetic recombinant technique disclosed by Zhu and the factsheet of rhNGF/rh-bNGF to the Lambiase’s method would have yielded the predictable result of obtaining NGF consisting of the amino acid sequence of instant SEQ ID NO:1 and treating glaucoma, and resulted in an improved method.
Using a NGF consisting of the known sequences of instant SEQ ID NO: 1 obtained by the known genetic recombinant technique in the Lambiase’s method would expand the sources and generation of NGF for therapeutic purposes, and obtain NGF consisting of the sequence of instant SEQ ID NO:1, and expand application of the Lambiase’s method for treating glaucoma, and would increase patient’s satisfaction with treatment of glaucoma using NGF or hNGF or hrNGF because NGF or hNGF or rhNGF can be obtained from a genetic recombinant technique to obtain hNGF or hrNGF consisting of instant SEQ ID NO:1 as taught by Zhu and the factsheet of rhNGF/rh-bNGF. Note that
“The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” See MPEP 2144.07.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known hNGF or rhNGF consisting of the known sequences of SEQ ID NO: 1 obtained by the known genetic recombinant technique disclosed by Zhu and the factsheet of rhNGF/rh-bNGF to the Lambiase’s method, and yield the predictable result of obtaining the hNGF or rhNGF consisting of the known sequences of SEQ ID NO: 1 by the known genetic recombinant technique disclosed by Zhu and the factsheet of rhNGF/rh-bNGF to the Lambiase’s method and treating glaucoma.
iv. Routine optimization of dose range disclosed by Lambiase would have led to the claimed ranges of 0.0001%-0.5% w/v or 0.001%-0.1% or 0.002% in claims 37-39 because Lambiase teaches NGF in a concentration of 1-1000ug/ml (0.0001%-0.1%) and Presta teaches composition comprising amounts of NGF from 0.07-20mg/ml (i.e. 0.007%-2%), 0.08-15mg/ml (i.e.0.008%-1.5%) or 0.09-10mg/ml (i.e. 0.009%-1%) or 0.1-2mg/ml (i.e.0.01%-0.2%). The person of ordinary skill in the art would have found it obvious to optimize within the range taught by Lambiase and Presta because Lambiase and Presta teach that this entire range for treating glaucoma, and also teaches how to optimize the dose ranges for treatment of glaucoma.
“[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”; “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969); Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert.denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). See MPEP § 2144.05.
v. In response to Applicant’s arguments related to superior results, note that evidence of unexpected results must be weighed against evidence supporting prima facie obviousness in making a final determination of the obviousness of the claimed invention. In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978). See MPEP 716.02(c)-I. Any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. See: MPEP §716.02. Further, evidence of unexpected results is frequently in the form of a direct comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims. See: e.g., In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980).
In this case, Applicants fails to provide sufficient evidence of side-by-side comparisons to demonstrate unexpected results as claimed because none of Examples 4 and 6-7 are related to a model of treatment of glaucoma or an art accepted animal model for evaluation of treatment of glaucoma. The examples 4 and 6-7 only showed: 1) in vitro neuronal differentiation of PC12 cells treated with rhNGF-118 compared to rhNGF-1 or rhNGF-120 (see p. 23, Example 4, figures 7 and 13); 2) in vitro proliferation of TF-1 cell line (erythroblasts) treated with rhNGF-118 compared to rhNGF-1 (p. 25-26, Example 6, table 11); and 3) reducing cell apoptosis induced by tBHP in human RPE cell line (ARPE-19) treated with rhNGF-118 compared to rhNGF-4. None of these examples are related to treatment of glaucoma or an art accepted animal model of evaluating treatment of glaucoma. No data demonstrates the use of rhNGF-118 for treatment of glaucoma. The specification provides no well-established structural and functional correlation between the data shown in examples 4 and 6-7 and the unexpected results obtained from the claimed invention as claimed. Since Applicant fails to provide any evidence as discussed above to support any unexpected results as claimed, the claimed method is obvious over the prior art, absent evidence to the contrary.
Accordingly, the rejection of claims 16 and 31-48 under 35 U.S.C. 103 as being unpatentable over Lambiase in view of Zhu and the factsheet of rhNGF/rh-bNGF is maintained.
Double Patenting
9. Claims 16 and 31-48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 9 of copending Application No. 18275849 (the ‘849 Application). The provisional rejection is maintained for the reasons of record and the reasons set forth below.
Response to Arguments
On p. 7 of the response, Applicant requests the rejection be held in abeyance until allowable subject matter is indicated.
In response, the provisional rejection of claims 16 and 31-48 on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 9 of copending Application No. 18275849 is maintained of record until a terminal disclaimer is filed.
New Grounds of Rejection Necessitated by the Amendment
The following rejections are new grounds of rejections necessitated by the amendment filed on September 22, 2025.
Claim Rejections - 35 USC § 102
10. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 16 and 31-48 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Imbimbo et al. (US2022/0401517, published Dec 22, 2022, priority Sep 17, 2019; also published as WO2021052926).
Imbimbo et al. (US2022/0401517) teaches a method for treating an ophthalmic disorder including glaucoma (see para. [0140]-[0142]; [0144]-[0146]; claim 13) in a mammalian subject including a human patient in need thereof (see para. [0013]; [0017]; claim 2), comprising administering to an eye of the subject or human patient (see para. [0013]) an ophthalmic preparation comprising a mature NGF or recombinant human NGF (rhNGF) polypeptide (see para. [0423], Example 6, [0427]-[0429]; [0072])at a concentration of 0.2-20mg/ml (i.e.0.02%-2%) or at a dose of 0.001-5ug/5ul/eye (0.00002%-0.1%) or 200ug/ml (see para. [0423], Example 6, [0427]-[0429];), wherein the mature NGF consists of the amino acid sequence of SEQ ID NO:2, which is 100% identical to instant SEQ ID NO:1 (see the sequence alignment below; para. [0404]- Example 5), which meets the limitations recited in claims 16 and 31-48. The ophthalmic preparation comprising a mature NGF or recombinant human NGF (rhNGF) polypeptide disclosed by Imbimbo meets the limitations recited in claims 16 and 43-48. Imbimbo teaches that mature NGF is in a liquid ophthalmic aqueous composition as recited in claims 33-35 and 37-39 (see para. [0404]; [0407]). Imbimbo teaches administering topically to the conjunctiva, which is the anterior segment of the eye in claim 36 (see para.[0023]; [0168];[0178]; [0197], claim 5), and intravitreal administration, which is administering to the posterior segment of the eye in claim 40 and an intravitreal injection as in claims 41-42 (see para. [0023]; [0168]; [0178]; [0247]; claim 5). The mature NGF is at a concentration of 0.3-30ug (0.03%-3%) or 1-10ug/eye or 5ug/5ul/eye (0.1%) or 0.5ug/5ul/eye (0.01%), 1ug/5ul/eye (0.02%), 5ug/5ug/eye or 10ug/5ul/eye (see para.[0027]-[0033]; [0197];[0407]-[0410], claim 14), which is within or overlapping with the claimed range of “ranging from about 0.0001~0.5% w/v of the aqueous composition” in claim 37, “0.001%-0.1% w/v” in claim 38 or “0.002% w/v” in claim 39. Thus, claims 16 and 31-48 are anticipated by Imbimbo et al. (US2022/0401517).
SEQ ID NO:1
Sequence 2, US/17753872
Publication No. US20220401517A1
GENERAL INFORMATION
APPLICANT: CHIESI FARMACEUTICI S.P.A.
APPLICANT: IMBIMBO, BRUNO PIETRO
APPLICANT: VILLETTI, GINO
TITLE OF INVENTION: AGENT FOR USE IN TREATMENT OR PREVENTION OF OPHTHALMIC DISORDERS
FILE REFERENCE: 4559.0270001
CURRENT APPLICATION NUMBER: US/17/753,872
CURRENT FILING DATE: 2022-03-16
PRIOR APPLICATION NUMBER: PCT/EP2020/075697
PRIOR FILING DATE: 2020-09-15
PRIOR APPLICATION NUMBER: EP 19197687.7
PRIOR FILING DATE: 2019-09-17
NUMBER OF SEQ ID NOS: 4
SEQ ID NO 2
LENGTH: 118
TYPE: PRT
ORGANISM: Homo sapiens
FEATURE:
NAME/KEY: MISC_FEATURE
LOCATION: (1)..(118)
OTHER INFORMATION: Sequence of mature human NGF
Query Match 100.0%; Score 642; Length 118;
Best Local Similarity 100.0%;
Matches 118; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRD 60
Qy 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVR 118
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVR 118
SEQ ID NO:1
ID BJC12369 standard; protein; 118 AA.
XX
AC BJC12369;
XX
DT 29-APR-2021 (first entry)
XX
DE Human nerve growth factor (NGF), SEQ ID: 2.
XX
KW Nerve growth factor ligand; glaucoma; glioma; keratitis; neuroprotective;
KW ocular disease; ophthalmological; optic nerve disorder; optic neuritis;
KW prophylactic to disease; retinopathy; therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2021052926-A1.
XX
CC PD 25-MAR-2021.
XX
CC PF 15-SEP-2020; 2020WO-EP075697.
XX
PR 17-SEP-2019; 2019EP-00197687.
XX
CC PA (CHIE ) CHIESI FARM SPA.
XX
CC PI Imbimbo BP, Villetti G;
XX
DR WPI; 2021-29774F/030.
XX
CC PT New polypeptide that is characterized by mutation of amino acid sequence
CC PT of human nerve growth factor (NGF), for treating and/or preventing
CC PT ophthalmic disorder, e.g. glaucoma, neurotrophic keratitis, and optic
CC PT pathway glioma.
XX
CC PS Example 5; SEQ ID NO 2; 105pp; English.
XX
CC The present invention relates to a polypeptide characterized by mutation
CC of human nerve growth factor (NGF), useful for treating and preventing
CC ophthalmic disorder. The polypeptides are administrated via topical
CC administration and intravitreal administration to the eye. The invention
CC is useful for treating and preventing an ophthalmic disorder in a
CC mammalian subject, where the ophthalmic disorder involves damage or a
CC disorder of the optic nerve and retinal ganglion cells; or selected from
CC glaucoma, neurotrophic keratitis, optic neuritis, optic nerve atrophy,
CC optic nerve head drusen and optic pathway glioma.
XX
SQ Sequence 118 AA;
Query Match 100.0%; Score 642; Length 118;
Best Local Similarity 100.0%;
Matches 118; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRD 60
Qy 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVR 118
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVR 118
Conclusion
11. NO CLAIM IS ALLOWED.
Sequence alignment
SEQ ID NO:2 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRD 60
SEQ ID NO:4 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRD 60
SEQ ID NO:1 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRD 60
SEQ ID NO:3 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRD 60
SEQ ID NO:2 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVRRA 120
SEQ ID NO:4 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVRR- 119
SEQ ID NO:1 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVR-- 118
SEQ ID NO:3 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAV--- 117
SEQ ID NO:1=118 aa
SEQ ID NO:2=120 aa
SEQ ID NO:3=117 aa
SEQ ID NO:4=119 aa
12. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US20210079053 teaches NGF having a 118-aa of instant SEQ ID NO:1 (see the sequence alignment below).
SEQ ID NO:1
US-17-050-252-2
(NOTE: this sequence has 8 duplicates in the database searched.
See complete list at the end of this report)
Sequence 2, US/17050252
Publication No. US20210079053A1
GENERAL INFORMATION
APPLICANT: Chiesi Farmaceutici S.p.A.
TITLE OF INVENTION: Production of Nerve Growth Factor (NGF) and of Muteins thereof
FILE REFERENCE: 028320-8020 (51-24 PCTUS)
CURRENT APPLICATION NUMBER: US/17/050,252
CURRENT FILING DATE: 2020-10-23
PRIOR APPLICATION NUMBER: EP 18 169 859.8
PRIOR FILING DATE: 2018-04-27
PRIOR APPLICATION NUMBER: PCT/EP2019/060733
PRIOR FILING DATE: 2019-04-26
NUMBER OF SEQ ID NOS: 4
SEQ ID NO 2
LENGTH: 118
TYPE: PRT
ORGANISM: Homo sapiens
Query Match 100.0%; Score 642; Length 118;
Best Local Similarity 100.0%;
Matches 118; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRD 60
Qy 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVR 118
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVR 118
US20220064243 teaches a NGF consisting of the amino acid sequence of SEQ ID NO:2, which is 100% identical to instant SEQ ID NO:1 (see the sequence alignment below).
SEQ ID NO:1
Sequence 2, US/17277240A
Publication No. US20220064243A1
GENERAL INFORMATION
APPLICANT: CHIESI FARMACEUTICI S.P.A.
APPLICANT: VILLETTI, GINO
APPLICANT: IMBIMBO, BRUNO PIETRO
APPLICANT: CALZA, LAURA
TITLE OF INVENTION: AGENT FOR TREATMENT OF DERMATOLOGICAL DISORDERS
FILE REFERENCE: 4559.0150002
CURRENT APPLICATION NUMBER: US/17/277,240A
CURRENT FILING DATE: 2021-09-07
PRIOR APPLICATION NUMBER: PCT/EP2019/074767
PRIOR FILING DATE: 2019-09-17
PRIOR APPLICATION NUMBER: EP 18203665.7
PRIOR FILING DATE: 2018-10-31
PRIOR APPLICATION NUMBER: EP 18194930.6
PRIOR FILING DATE: 2018-09-17
NUMBER OF SEQ ID NOS: 4
SEQ ID NO 2
LENGTH: 118
TYPE: PRT
ORGANISM: Homo sapiens
FEATURE:
OTHER INFORMATION: Mature human NGF
Query Match 100.0%; Score 642; Length 118;
Best Local Similarity 100.0%;
Matches 118; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRD 60
Qy 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVR 118
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVR 118
US12378293 teaches a NGF consisting of the amino acid sequence of SEQ ID NO:2, which is 100% identical to instant SEQ ID NO:1 (see the sequence alignment below).
SEQ ID NO:1
Sequence 2, US/17050252
Patent No. 12378293
GENERAL INFORMATION
APPLICANT: Chiesi Farmaceutici S.p.A.
TITLE OF INVENTION: Production of Nerve Growth Factor (NGF) and of Muteins thereof
FILE REFERENCE: 028320-8020 (51-24 PCTUS)
CURRENT APPLICATION NUMBER: US/17/050,252
CURRENT FILING DATE: 2020-10-23
PRIOR APPLICATION NUMBER: EP 18 169 859.8
PRIOR FILING DATE: 2018-04-27
PRIOR APPLICATION NUMBER: PCT/EP2019/060733
PRIOR FILING DATE: 2019-04-26
NUMBER OF SEQ ID NOS: 4
SEQ ID NO 2
LENGTH: 118
TYPE: PRT
ORGANISM: Homo sapiens
Query Match 100.0%; Score 642; Length 118;
Best Local Similarity 100.0%;
Matches 118; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRD 60
Qy 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVR 118
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVR 118
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached Monday-Thursday, 7:00am-5:00pm EST.
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, Jeffrey Stucker can be reached at 571-272-0911. 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.
Chang-Yu Wang
September 29, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
Prosecution Insights