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 .
Response to Amendment
Applicant's response filed 26 January 2026 has been received and entered. Claims 1, 3, 5, 14, 18-20, 22-25 and 28 are currently amended, claims 29-40 have been newly added and claims 6, 8-1013, 15-17 and 26-27 have been canceled. Claims 1-5, 7, 11-12, 14, 18-25 and 28-40 are currently pending and under consideration in the instant Office action.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Any objection or rejection of record which is not expressly repeated in this action has been overcome by Applicant's response and withdrawn.
Applicant's arguments filed 26 January 2026 have been fully considered but are not found to be persuasive.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. (see specification beginning at page 66)
The information disclosure statement (IDS) submitted on 26 January 2026 has been considered by the examiner.
Drawings
The drawings are objected to because they do not comply with 37 CFR 1.84. The drawings (Figures 7-12, 14-66) are not in black and white with solid black lines, which must be used for drawings (see 37 CFR 1.84(a)(1)). See screenshot below:
The dotted nature of the lines is evident and the result is loss of clarity as well as a lack of solid black lines.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The title is not reflective of the claims which are directed to treatment with 8 mg doses of aflibercept.
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The abstract of the disclosure is objected to because it is not a concise statement of the invention as the invention is defined by the claims. The claims are limited to treatment with 8 mg dose of aflibercept. The abstract should reflect these elements as they are clearly components of the invention. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The use various terms, which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
EYLEA® is found throughout the disclosure, however, the generic terminology is not provided until [0096]. While EYLEA® is properly denoted in [0005], it is not properly referenced elsewhere (see at least [0007], [0079], [0212], [0226]). This list may not be complete and therefore, the specification should be reviewed carefully for compliance.
Tono pen™ is found at [0188]. While the mark is included, it does not appear to be properly capitalized and generic terminology is not provided.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The disclosure is objected to because of the following informalities:
The specification is replete with the abbreviation “HD”. The first usage is found in [0014] but it is not defined. [0079] equates “HD” to 8 mg dose, but the text still does not spell out what “HD” stands for. HD may refer to “high dose” however, “high dose” also appears to be limited to 8 mg so a limiting definition of what is intended is necessary to understand the meaning of the abbreviation.
All abbreviations should be defined at their first usage for the sake of clarity. ETDRS is found in [0009] but is not defined until [0018].
The Brief Description of the Drawings is objected to because Figures 25A-25C, 38A-38C, 43A-43B, 44A-44B are not properly identified. The Brief Description only refers to 25, 38, 43 and 44 and fails to indicate the subparts. Correction is required.
Paragraph [0010] of the specification refers to “A-KKKK”: This passage is confusing because there is no statement of what “A-KKKK” is intended to mean. There is a list of formulations in paragraph [0112] which begin with “A” and end with “KKKK”, but without clearly stating that the subject matter of 0112] is what is being referenced in [0010], the disclosure is confusing.
Paragraph [0223] recites “…a formulation including aflibercept (REGN3) at a concentration of 114.3 mg/ml”. This recitation is confusing because it is not clear if “(REGN3)” is a short-hand notation for aflibercept or if it is a specific formulation which is not defined. REGN3 is not defined in the specification
The specification contains several Tables (1-1, 1-2 and 1-3) which are unreadable (see [0160], [0184] and [0186]). The font size may not be compliant (too small) with 37 CFR 1.52(b)(2)(ii). If the font size is appropriate, the text is not compliant as the text is not formed by solid black lines having sufficient contrast between the text and the paper. See screenshot below from Table 1-2 as exemplary:
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Appropriate correction is required.
Claim Objections
Claim 31 is objected to because of the following informalities: the eye disorders in the claim are capitalized however, these conditions are not capitalized in the art. 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 2 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.
The items recited in part (i) are not compatible with the recitation of “and/or”. It would not be possible to have no loss in visual acuity AND a gain in visual acuity AND maintenance of visual acuity in the same patient as these are different end points. Parts (ii) and (iii) do not indicate if the listed elements are in the alternative or not and therefore, the metes and bounds of (ii) and (iii) cannot be determined (are all parts of (ii) and (iii) required or not. Part (iii) ends with two recitations of “and/or” so it is not clear what is the intent of the second “and/or” .
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 2 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 2 recites the possible outcomes of treatment with the method of claim 1; “wherein, while receiving said treatment….the subject achieves…” However, claim 2 does not appear to further limit the subject matter of claim 1 because treatment with intravitreal injection of aflibercept will inherently result in the outcomes which are recited in claim 2. Therefore, claim 2 does not materially limit the subject matter of claim 1 unless one would expect that a subject being treated with the method of claim 1 will not respond to the treatment and the angiogenic eye disorder will worsen. However, based on the disclosure in the specification, this does not appear to be a realistic outcome and therefore, claim 2 does not materially limit the subject matter of claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claim(s) 1-5, 7, 11-12, 14, 18-25 and 29-40 are is/are rejected under 35 U.S.C. 103 as being unpatentable over US PGPub 2019/0343918 A1 (Graham et al.) in view of WO 2012/097019 (Yancopoulos).
Graham et al. is directed to high concentration formulations of a VEGF receptor fusion protein, aflibercept. Graham et al. state at [0005] that “[h]igher concentration antibody formulations allow for shorter injection times, smaller injection volumes, lower frequency of antibody administration” and that high “concentration VEGF receptor fusion protein containing formulations could allow for shorter ocular injection times, smaller injection volumes, fewer possible injections per administration cycle” (see [0006]).
Graham et al. teach pharmaceutical formulations of aflibercept wherein a single dose is in less than about 100µl (less than about 50, about 50, about 57, about 60, about 70 or about 75µl (see [0010]) (see instant claims 18, 24-25, 29, 32). Graham et al. teach that the formulations can be administered in a pre-filled syringe (see [0033] which can be sterile (see [0290]), glass or polymer (see [0293]) and utilizing a ½ inch, 30-guage injection needle (see [0281] and [0299]) (see instant claims 20, 28, 33-34). Graham et al. teach that the volume to be administered is less than or equal to about 100 microliters; about 60, 70 or 75 microliters (see [0281] and instant claims 24-25). Graham et al. specifically exemplify a concentration of 114.3 mg/ml VEGF receptor fusion protein (e.g., aflibercept) (see [0242]: Formulation GGGG: 114.3 mg/ml VEGF receptor fusion protein (e.g., aflibercept) (e.g., 103- 126 mg/ml), 10 mM histidine-based buffer (e.g., +1 mM), 5% (w/v) sucrose (e.g., +0.5%), 0.03% (w/v) polysorbate 20 (e.g., 0.02-0.04%), and 50 mM L-arginine monohydrochloride (e.g., +5 mM), with a pH of 5.8 (e.g., 5.6-6.0 or 5.5-6.1)). This concentration is the same as instant claim 19, 29 and 30 and the formulation is the same as instant claims 29-30 [see 0242]. Graham et al. also teach that formulations have less than about 3.5% increase in high molecular weight species immediately after manufacture (see [0126] and less than or equal to about 6% high molecular weight species after storage for about 24 months at about 2-8°C (see []0031]) (see instant claim 29). Graham et al. teach that the formulations have a viscosity of from about 10 cP to about 15 cP at 20°C (e.g., about 6.0, 7.3, 11.5 or 12.0 cP at 20°C) (see [0030] of Graham et al. and instant claim 36) and an osmolality of from about 250 to about 506 mmol/Kg (see [0121] of Graham et al. and instant claim 37). Graham et al. teach a variety of buffers for the disclosed formulation with a variety of pH ranges, wherein the recited range depends on the buffer system which is used (see [0013]), but Graham et al. clearly encompass a range of about 5.8 to about 6.5 (see instant claim 38) with a specific pH of about 5.8 (see Table A, Formulations F1-F12 of Graham et al.) and 6.0 (see [0036]) (see instant claims 39-40).
Graham et al. teach that the high concentration VEGF receptor fusion protein formulations can be used to treat angiogenic eye disorders which include the angiogenic eye disorders listed in instant claim 12 (see [0036] of Graham et al.). Graham et al. teach a method of treating an angiogenic eye disorder in a subject in need thereof by intraocularly injecting at least about 2 mg (e.g., 4, 6 or 8.0, 8.1, 8.4 or 8.5 mg ) of VEGF receptor fusion protein (e.g., aflibercept) into the eye of a subject in need thereof. Graham et al. further teach administering a therapeutically effective amount of VEGF receptor fusion protein (e.g., aflibercept)(e.g., about 4, 6, or 8.0, 8.1, 8.4 or 8.5 mg) “in a pharmaceutical formulation according to the present invention, intraocularly” (see [0278] and claim 33 of Graham et al.). Graham et al. teaches that the concentration of any formulation constituent, including the dose of aflibercept, is ± about 3%, 5% or about 10% of the concentration specifically mentioned (see [0248] and instant claim 23). Graham et al. continues that the formulation is administered every 2-24 weeks (see [0278]).
Graham et al. teaches that “treat” or “treatment” refers to a therapeutic measure that reverses, stabilizes or eliminates an undesired disease/disorder, e.g. “with regard to an angiogenic eye disorder, by causing a reduction in or maintenance of diabetic retinopathy severity score (DRSS), by improving or maintaining vision (e.g., in best corrected visual acuity e.g., as measured by an increase in ETDRS letters), increasing or maintain visual field and/or reducing or maintaining central retinal thickness” (see [0077] and [0284]) (see instant claim 2).
Instant claim 5 (and 14) refers to “promoting retinal drying” or “achieving a dry retina”. However, retinal drying describes the resolution of fluid buildup in the macula which is achieved by anti-VEGF treatments in the eye, which is well-known in the art before the effective filing date of the claimed invention. Inhibition of VEGF in the eye shrinks abnormal, leaky blood vessels and reduced vascular permeability in subjects with angiogenic eye disease, which is the basis for anti-VEGF therapy for treating angiogenic eye disease. While Graham et al. does not specifically recite “promoting retinal drying” or “achieving a dry retina”, this result is inherent to the administration of intravitreal injection of a VEGF inhibitor (e.g., aflibercept).
Graham et al. does not teach the specific dosing regimen of an initial dose, followed by one or more secondary doses, followed by one or more tertiary doses wherein the secondary dose is administered about 2 to 4 weeks after the immediately preceding dose and wherein the tertiary dose is administered about 4, 8 or 12 weeks after the immediately preceding dose. Graham et al. does not teach administering one or more additional pro re nata doses (claim 11). Graham et al. also does not teach that the subject being treated in the claimed method does not have ocular infection and/or periocular infection (claim 35).
Yancopoulos teaches the treatment of angiogenic eye diseases by sequentially administering multiple doses of a VEGF antagonist to a patient over time (see [0005]). Yancopoulos teaches that the method can be used to treat any angiogenic eye disorder (see [0006]), and according to the method disclosed, following an initial dose, each secondary dose of VEGF antagonist is administered 2 to 4 weeks after the immediately preceding dose, and each tertiary dose is administered at least 8 weeks after the immediately preceding dose (see also Figure 1). Yancopoulos teaches that one advantage of such a dosing regimen is that, for most of the course of treatment (i.e., the tertiary doses), it allows for less frequent dosing compared to prior administration regimens for angiogenic eye disorders which require monthly administrations throughout the entire course of treatment (see [0005]). While Yancopoulos exemplifies administration of the tertiary dose at a frequency of every 8 weeks, Yancopoulos teaches that the tertiary dose is administered at least 8 (e.g., 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5 or more) weeks after the immediately preceding dose (see [0017]). Yancopoulos also teaches that the frequency of administration may be adjusted by a physician depending on the needs of the individual patient following clinical examination (see [0020]). The VEGF antagonist which is exemplified by Yancopoulos is commonly known as aflibercept (see [0023]; referred to as VEGFT (which is short for VEGF Trap). The method of Yancopoulos administers a dose of VEGF antagonist which is about 0.05 mg to about 5 mg (see [0030]) and exemplifies various doses including 0.5, 2 and 4 mg (see at least Example 2). Yancopoulos also teaches the exclusion of patients from the disclosed method who have active intraocular inflammation in either eye, active ocular or periocular invention in either eye (see page 12, bottom of page, #’s 18-20). While Yancopoulos discloses a particular dosing regimen, Yancopoulos teaches that the frequency of administration may be adjusted by a physician depending on the needs of the individual patient following clinical examination (see [0020]) and in Example 5 Yancopoulos administers the VEGF antagonist “either once every 8 weeks dosing (2Q8) or as needed dosing with very strict repeat dosing criteria (PRN)” as well as administering “2 mg VEGFT as-needed (PRN) according to retreatment criteria” (see [0062]-[0065]; see instant claim 11).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to treat a subject suffering from angiogenic eye disease with the compositions of Graham et al. because Graham et al. teach that high concentration formulations of a VEGF receptor fusion protein, e.g. aflibercept, allow for shorter ocular injection times, smaller injection volumes, and fewer possible injections per administration cycle when treating angiogenic eye conditions. Graham et al. teach the administration of 8 mg of aflibercept for treating angiogenic eye disorders as well as administration in a volume of less than 100 µl, including in a volume of about 70 µl. Graham et al. additionally teach various aqueous pharmaceutical formulations for administration which are identical to those recited in the instant claims as well as the therapeutic outcomes which would be achieved by treatment of an angiogenic eye disorder. Graham et al. further teach administering a therapeutically effective amount of VEGF receptor fusion protein (e.g., aflibercept), in a pharmaceutical formulation according to the present invention, intraocularly, and that the formulation is administered every 2-24 weeks. While Graham et al. does not teach the dosing regimen of the instant claims, it would have been prima facie obvious to one of ordinary skill in the art before the filing date of the instant claims to adopt the dosing regimen taught by Yancopoulos because Yancopoulos teaches the advantages of the disclosed dosing regimen for treating the same condition (angiogenic eye disease) with the same therapeutic compound (aflibercept). Additionally, it would have been obvious to one of ordinary skill in the art to exclude subjects from the treatment of Graham et al. who have ocular or periocular infection or inflammation because Yancopoulos teaches that such subjects should not be treated. One would have been motivated to adopt the dosing regimen of Yancopoulos when practicing the method of Graham et al. because Yancopoulos teach that such a dosing regimen allows for less frequent dosing compared to other prior dosing regimens for other therapeutics used for treating angiogenic eye disease. One of ordinary skill in the art would have readily appreciated the advantage because reducing the number of intraocular injections for a therapeutic effect would not only reduce the number of visits for treatment, but would also reduce the amount of discomfort a given patient would need to endure. One of ordinary skill in the art would have had a reasonable expectation of success in applying the dosing regimen of Yancopoulos to the method of Graham et al. because the same therapeutic compound is being administered for treating the same conditions. Yancopoulos teaches the combination of initial dose/secondary doses/tertiary doses and number of weeks (i.e. 2 secondary doses every 4 weeks followed by one or more tertiary doses administered at least 8 weeks after the immediately preceding dose encompassed by the instant claims, therefore, the disclosure of Yancopoulos clearly encompasses the various combinations recited in the instant claims. Additionally, it would have been well within the skill of the artisan at the time of the instant invention to explore various interval timings and arrive at applicant’s claimed invention with a reasonable expectation of success, including administering the tertiary dose every 4 weeks as encompassed by the instant claims. In addition, dosage amounts or concentrations of drugs and length of administrations etc., are result effective variables, because a skilled person in the art determines these variables through a routine experimentation and which is common practice in the art, absent evidence to the contrary. Generally, differences in concentrations of components of a formulation (or drug or tuning length of interval) will not support the patentability of subject matter encompassed by the prior art. Such formulations are results-effective variables which can be optimized. In In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980), it was held that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Further, in In re Aller, 220 F. 2d454, 456, 105 USPQ 233,235 (CCPA 1955) the courts maintained that: "Where the general condition of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." As formulating optimal compositions for medicaments is routine in the art of pharmacology, the claims are considered to be prima facie obvious.
See Tyco Healthcare Group LP V. Mutual Pharmaceutical Co., 642 F.3d 1370 (Fed. Cir. 2011) ("the court observed that the parties did not dispute that 'physicians always seek to prescribe the lowest effective dose of any medication"). "[t]he test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art." See In re Keller, 642 F.2d 413, 425 (CCPA 1981).
Claim(s) 1 and 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over US PGPub 2019/0343918 A1 (Graham et al.) in view of WO 2012/097019 (Yancopoulos) as applied to claim 1 above, and further in view of WO 2019/118588 (Ulla et al.) (cited in the instant specification).
The disclosures of Graham et al. and Yancopoulos are provided above. Neither Graham et al. nor Yancopoulos teach a method of intravitreal injection with a pre-filled syringe that comprises the specific method steps recited in instant claim 28 (priming the syringe, rotating the plunger rod, etc.).
Ulla et al. disclose syringes which can be pre-filled and methods of administering compositions with the disclosed pre-filled syringes. Ulla et al. specifically teaches the syringes of their disclosure may be used with products having small dose volumes, such as ophthalmic drugs, including aflibercept (see [046]) and that the syringes are configured to promote precision dose delivery (see [002]). Claims 31-32 and 34 of Ulla et al. recite a method of administering a composition with the disclosed syringe wherein the steps of Ulla et al. meet the limitations of the steps in instant claim 28 (dispensing a substance from a drug delivery device having a plunger rod and a barrel, comprising advancing the plunger rod by a predetermined distance into the barrel until advancement of the plunger rod is resisted by a stop, deactivating the stop and actuating the plunger rod to deliver the substance, wherein deactivating the stop comprises rotating the plunger rod). .
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to practice the method of Graham et al. utilizing the dosing regimen of Yancopoulos for the treatment of an angiogenic eye disorder and administering the dose of aflibercept using the pre-filled syringe of Ulla et al. because Ulla et al. teach that the syringe promotes precision dose delivery and the syringe can be pre-filled. One would be motivated to use the syringe of Ulla et al. and follow the method steps for dispensing the drug contained therein because Ulla et al. teach that drugs which are administered at low volumes would be ideal for use in the syringes and because Ulla et al. teach use with ophthalmic drugs, including aflibercept (see [046]). Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, absent evidence to the contrary.
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 1-5, 7, 11-12, 14, 18-25 and 29-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 17-20, 28-33 and 36 of U.S. Patent No. 11,103,552 in view of WO 2012/097019 (Yancopoulos). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the claims of ‘552 in view of Yancopoulos.
‘552 is directed to a method of treating an angiogenic eye disorder in a subject in need thereof (claim 17) by administering an aqueous pharmaceutical formulation comprising aflibercept (claim 1), wherein about 8 mg is administered (claims 18, 29 and 33) and wherein the formulation of ‘552 is of the same scope as that of the instant claims. ‘552 does not claim a particular dosing regimen as recited in the instant claims but does claim administration wherein the fusion protein is administered every 8-24 weeks. However, the dosing regimen of the instant claims would have been obvious over the claims of ‘552 in view of Yancopoulos for the reasons provided above in the 103 rejection. Therefore, the instant claims are not patentably distinct from those of ‘552 in view of Yancopoulos.
Claims 1 and 28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 17-20, 28-33 and 36 of U.S. Patent No. 11,103,552 in view of WO 2012/097019 (Yancopoulos) and further in view of WO 2019/118588 (Ulla et al.). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the claims of ‘552 in view of Yancopoulos and further in view of Ulla et al.
The disclosures of ‘552 and Yancopoulos are provided above. Neither ‘552 nor Yancopoulos teach a method of intravitreal injection with a pre-filled syringe that comprises the specific method steps recited in instant claim 28 (priming the syringe, rotating the plunger rod, etc.). Ulla et al. disclose syringes which can be pre-filled and methods of administering compositions with the disclosed pre-filled syringes. Ulla et al. specifically teaches the syringes of their disclosure may be used with products having small dose volumes, such as ophthalmic drugs, including aflibercept (see [046]) and that the syringes are configured to promote precision dose delivery (see [002]). Claims 31-32 and 34 of Ulla et al. recite a method of administering a composition with the disclosed syringe wherein the steps of Ulla et al. meet the limitations of the steps in instant claim 28 (dispensing a substance from a drug delivery device having a plunger rod and a barrel, comprising advancing the plunger rod by a predetermined distance into the barrel until advancement of the plunger rod is resisted by a stop, deactivating the stop and actuating the plunger rod to deliver the substance, wherein deactivating the stop comprises rotating the plunger rod). .
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to practice the method of ‘552 utilizing the dosing regimen of Yancopoulos for the treatment of an angiogenic eye disorder and administering the dose of aflibercept using the pre-filled syringe of Ulla et al. because Ulla et al. teach that the syringe promotes precision dose delivery and the syringe can be pre-filled. One would be motivated to use the syringe of Ulla et al. and follow the method steps for dispensing the drug contained therein because Ulla et al. teach that drugs which are administered at low volumes would be ideal for use in the syringes and because Ulla et al. teach use with ophthalmic drugs, including aflibercept (see [046]). Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, absent evidence to the contrary.
Claims 1-5, 7, 11-12, 14, 18-25, 29-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 of U.S. Patent No. 12,168,036 in view of WO 2012/097019 (Yancopoulos). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the claims of ‘036 in view of Yancopoulos.
‘036 is directed to a method of treating an angiogenic eye disorder in a subject in need thereof (claim 1) by administering an aqueous pharmaceutical formulation comprising aflibercept (claim 12), wherein about 8 mg is administered (claims 1). ‘036 claims limitations on the formulation which is to be administered, which are all limitations in the instant claims such as vicosity and presence of a sugar in the formulation as well as specific disorders to be treated. ‘036 does not claim a particular dosing regimen as recited in the instant claims. However, the dosing regimen of the instant claims would have been obvious over the claims of ‘036 in view of Yancopoulos for the reasons provided above in the 103 rejection. Therefore, the instant claims are not patentably distinct from those of ‘036 in view of Yancopoulos.
Claims 1 and 28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 12 of U.S. Patent No. 12,168,036 in view of WO 2012/097019 (Yancopoulos) and further in view of WO 2019/118588 (Ulla et al.). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the claims of ‘552 in view of Yancopoulos and further in view of Ulla et al.
The disclosures of ‘036 and Yancopoulos are provided above. Neither ‘036 et al. nor Yancopoulos teach a method of intravitreal injection with a pre-filled syringe that comprises the specific method steps recited in instant claim 28 (priming the syringe, rotating the plunger rod, etc.). Ulla et al. disclose syringes which can be pre-filled and methods of administering compositions with the disclosed pre-filled syringes. Ulla et al. specifically teaches the syringes of their disclosure may be used with products having small dose volumes, such as ophthalmic drugs, including aflibercept (see [046]) and that the syringes are configured to promote precision dose delivery (see [002]). Claims 31-32 and 34 of Ulla et al. recite a method of administering a composition with the disclosed syringe wherein the steps of Ulla et al. meet the limitations of the steps in instant claim 28 (dispensing a substance from a drug delivery device having a plunger rod and a barrel, comprising advancing the plunger rod by a predetermined distance into the barrel until advancement of the plunger rod is resisted by a stop, deactivating the stop and actuating the plunger rod to deliver the substance, wherein deactivating the stop comprises rotating the plunger rod). .
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to practice the method of ‘036 utilizing the dosing regimen of Yancopoulos for the treatment of an angiogenic eye disorder and administering the dose of aflibercept using the pre-filled syringe of Ulla et al. because Ulla et al. teach that the syringe promotes precision dose delivery and the syringe can be pre-filled. One would be motivated to use the syringe of Ulla et al. and follow the method steps for dispensing the drug contained therein because Ulla et al. teach that drugs which are administered at low volumes would be ideal for use in the syringes and because Ulla et al. teach use with ophthalmic drugs, including aflibercept (see [046]). Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, absent evidence to the contrary.
Claims 1-5, 7, 11-12, 14, 18-25 and 29-40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 25-54 of copending Application No. 18/121,499 (reference application) in view of WO 2012/097019 (Yancopoulos). Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to treatment of angiogenic eye disease with the exact same therapeutic agent and formulations with a similar dosing regimen comprising an initial dosage followed by one or more secondary doses followed by one or more tertiary dosages. The instant claims and the claims of ‘499 differ in the timing of the tertiary dose (the instant claims administer the tertiary dose about 4, 8 or 12 weeks after the immediately preceding dose while the claims of ‘499 administer the tertiary dose about 13-16 weeks after the immediately preceding dose). However, it would have been well within the skill of the artisan at the time of the instant invention to explore various interval timings and arrive at applicant’s claimed invention with a reasonable expectation of success, including administering the tertiary dose every 12 or more weeks as encompassed by the instant claims. In addition, dosage amounts or concentrations of drugs and length of administrations etc., are result effective variables, because a skilled person in the art determines these variables through a routine experimentation and which is common practice in the art, absent evidence to the contrary. The claims of the instant application and the claims of ‘499 also differ in that the instant claims are directed to treating an angiogenic eye disorder while the claims of ‘499 are directed to treating neovascular age-related macular degeneration (nAMD). While the instant claims are generically directed to treating an angiogenic eye disorder, instant claim 12 recites that the angiogenic eye disorder is neovascular age-related macular degeneration. While the conditions which are being treated are distinct, the instant claims would have been obvious over the claims of ‘499 because the prior art of Yancopoulos teaches that angiogenic eye diseases in general and including nAMD can be treated by administration of a VEGF antagonist (e.g. aflibercept) (see [0001] of Yancopoulos). The instant claims also recite that particular therapeutic outcomes are to be achieved by the method of treatment which are not recited in the claims of ‘490, however, because the same compounds/compositions are being administered to the same patient population, these outcomes would also be realized by the subjects of the instant claims. Therefore, the instantly claimed method of treating angiogenic eye disorders any of the other conditions listed in claim 12 would have been obvious over the claims of ‘499 directed to treating nAMD because the method of ‘499 is applicable to any and all angiogenic eye diseases as taught by Yancopoulos. Therefore, the instant claims are not patentably distinct from those of ‘499.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 25 of copending Application No. 18/121,499 (reference application) in view of WO 2012/097019 (Yancopoulos) and further in view of WO 2019/118588 (Ulla et al.). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the claims of ‘499 in view of Yancopoulos and further in view of Ulla et al.
The disclosures of ‘499 and Yancopoulos are provided above. Neither ‘499 nor Yancopoulos teach a method of intravitreal injection with a pre-filled syringe that comprises the specific method steps recited in instant claim 28 (priming the syringe, rotating the plunger rod, etc.). Ulla et al. disclose syringes which can be pre-filled and methods of administering compositions with the disclosed pre-filled syringes. Ulla et al. specifically teaches the syringes of their disclosure may be used with products having small dose volumes, such as ophthalmic drugs, including aflibercept (see [046]) and that the syringes are configured to promote precision dose delivery (see [002]). Claims 31-32 and 34 of Ulla et al. recite a method of administering a composition with the disclosed syringe wherein the steps of Ulla et al. meet the limitations of the steps in instant claim 28 (dispensing a substance from a drug delivery device having a plunger rod and a barrel, comprising advancing the plunger rod by a predetermined distance into the barrel until advancement of the plunger rod is resisted by a stop, deactivating the stop and actuating the plunger rod to deliver the substance, wherein deactivating the stop comprises rotating the plunger rod). .
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to practice the method of ‘499 utilizing the dosing regimen of Yancopoulos for the treatment of an angiogenic eye disorder and administering the dose of aflibercept using the pre-filled syringe of Ulla et al. because Ulla et al. teach that the syringe promotes precision dose delivery and the syringe can be pre-filled. One would be motivated to use the syringe of Ulla et al. and follow the method steps for dispensing the drug contained therein because Ulla et al. teach that drugs which are administered at low volumes would be ideal for use in the syringes and because Ulla et al. teach use with ophthalmic drugs, including aflibercept (see [046]). Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, absent evidence to the contrary.
Claims 1-5, 7, 11-12, 14, 18-25 and 29-40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 25-54 of copending Application No. 18/121,490 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the methods of the instant claims are anticipated by the claims of ‘490. The claims of the instant application and those of ‘490 administer the same compositions for the same purpose, treatment of angiogenic eye disorders. While the instant claims are directed to angiogenic eye disorders, claim 12 necessarily includes diabetic macular edema (DME) which the claims of ‘490 are directed. The instant claims recite that particular therapeutic outcomes are to be achieved by the method of treatment which are not recited in the claims of ‘490, however, because the same compounds/compositions are being administered to the same patient population, these outcomes would also be realized by the subjects of the instant claims. The instant claims recite that the tertiary dose is administered about 4, 8 or 12 weeks after the immediately preceding dose while the claims of ‘490 recite this interval as being about 13-16 weeks (+/- 5 days). However, the recited ranges overlap at the lower end of ‘490 and the upper end of the instant range. Additionally, the instant claimed interval for the tertiary administration of 4, 8 or 12 weeks would have been obvious in view of the claims of ‘490 because it would have been well within the skill of the artisan at the time of the instant invention to explore various interval timings and arrive at the claimed range with a reasonable expectation of success. In addition, dosage amounts or concentrations of drugs and length of administrations etc., are result effective variables, because a skilled person in the art determines these variables through a routine experimentation and which is common practice in the art, absent evidence to the contrary. One of ordinary skill in the art would have been motivated to extend the interval of the tertiary administration because intraocular injections are uncomfortable and require in person visits to the physician who is administering the treatment and increasing the interval would be advantageous for this reason. Therefore, the instant claims are not patentably distinct from those of ‘490.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 25 of copending Application No. 18/121,490 (reference application) in view of WO 2012/097019 (Yancopoulos) and further in view of WO 2019/118588 (Ulla et al.). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the claims of ‘499 in view of Yancopoulos and further in view of Ulla et al.
The disclosures of ‘490 and Yancopoulos are provided above. Neither ‘490 nor Yancopoulos teach a method of intravitreal injection with a pre-filled syringe that comprises the specific method steps recited in instant claim 28 (priming the syringe, rotating the plunger rod, etc.). Ulla et al. disclose syringes which can be pre-filled and methods of administering compositions with the disclosed pre-filled syringes. Ulla et al. specifically teaches the syringes of their disclosure may be used with products having small dose volumes, such as ophthalmic drugs, including aflibercept (see [046]) and that the syringes are configured to promote precision dose delivery (see [002]). Claims 31-32 and 34 of Ulla et al. recite a method of administering a composition with the disclosed syringe wherein the steps of Ulla et al. meet the limitations of the steps in instant claim 28 (dispensing a substance from a drug delivery device having a plunger rod and a barrel, comprising advancing the plunger rod by a predetermined distance into the barrel until advancement of the plunger rod is resisted by a stop, deactivating the stop and actuating the plunger rod to deliver the substance, wherein deactivating the stop comprises rotating the plunger rod). .
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to practice the method of ‘490 utilizing the dosing regimen of Yancopoulos for the treatment of an angiogenic eye disorder and administering the dose of aflibercept using the pre-filled syringe of Ulla et al. because Ulla et al. teach that the syringe promotes precision dose delivery and the syringe can be pre-filled. One would be motivated to use the syringe of Ulla et al. and follow the method steps for dispensing the drug contained therein because Ulla et al. teach that drugs which are administered at low volumes would be ideal for use in the syringes and because Ulla et al. teach use with ophthalmic drugs, including aflibercept (see [046]). Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, absent evidence to the contrary.
Claims 1-5, 7, 11-12, 14, 18-25 and 29-40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8, 13, 20-27, 33, 35, 38, 40-42, 45, 47, 49, 50, 52-67, 74-77, 79-83 of copending Application No. 18/751,087 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons. Both sets of claims are generally directed to methods of treating angiogenic eye disorders, the method comprising administering a high dose (including 8 mg) of a VEGF receptor fusion protein such as aflibercept at repeated intervals. The main difference between the claim sets is a difference in dosing frequency. The instant claim set recites a single initial dose, followed by one or more secondary doses about 2-4 weeks after the immediately preceding dose, followed by one or more tertiary doses about 4, 8 or 12 weeks after the immediately preceding dose. The copending claims recite a different range of dosing frequencies, but include, a single initial dose followed by one or more
secondary doses about 2, 3, or 4 weeks after the immediately preceding dose, followed by one or more tertiary doses at about 16-24 weeks after the immediately preceding dose. While the ranges of the tertiary doses do not overlap, the instantly claimed interval for the tertiary administration of 4, 8 or 12 weeks would have been obvious in view of the claims of ‘087 because it would have been well within the skill of the artisan at the time of the instant invention to explore various interval timings and arrive at the claimed range with a reasonable expectation of success. In addition, dosage amounts or concentrations of drugs and length of administrations etc., are result effective variables, because a skilled person in the art determines these variables through a routine experimentation and which is common practice in the art, absent evidence to the contrary. One of ordinary skill in the art would have been motivated to extend the interval of the tertiary administration because intraocular injections are uncomfortable and require in person visits to the physician who is administering the treatment and increasing the interval would be advantageous for this reason. Therefore, the instant claims are not patentably distinct from those of ‘087.
The claim sets also differ in that ‘087 recites effects achieved by the administrations. However, since the copending claims fairly suggest administering the same active agent to treat the same diseases, it can be assumed that the effects of the administrations would have been inherent to the method.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-5, 7, 11-12, 14, 18-25 and 29-40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 62-66, 69, 73, 77 and 81 of copending Application No. 18/367,444 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons. Both sets of claims are generally directed to methods of treating angiogenic eye disorders including diabetic macular edema, the method comprising administering about 8 mg of a VEGF receptor fusion protein (aflibercept). ‘444 does not claim a particular dosing regimen as recited in the instant claims. However, the dosing regimen of the instant claims would have been obvious over the claims of ‘444 in view of Yancopoulos for the reasons provided above in the 103 rejection. Therefore, the instant claims are not patentably distinct from those of ‘444 in view of Yancopoulos.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant argues the obvious-type double patenting rejections over 18/751,087, 18/121,499 and 18/121,490 by asserting that the amended claims do not explicitly overlap and therefore the claims are patentably distinct. Applicant’s arguments have been fully considered, but are not found persuasive. The claims have been rejected over prior art (new grounds of rejection) as well as the amended claims being rejected on the basis of obviousness-type double patenting as set forth above. As some of the rejections were not necessitated by Applicant’s amendment, the instant office action has not been made final.
Conclusion
No claim is allowed.
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/Christine J Saoud/Primary Examiner, Art Unit 1645
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