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 of rifamycin as the elected rifamycin compound and buffer salt as the elected pharmaceutically acceptable carrier in the reply filed on 04/09/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Priority
This application is a U.S. National Phase Application under 35 U.S.C. §371 of
International Patent Application No. PCT/JP2021/047323 filed on December 21, 2021, which claims priority to Japanese Patent Application No. 2020-211571 filed on December 21, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/19/2026 has been considered by the examiner.
Status of Claims
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on August 19, 2026. Claims 1-11 and new claims 12-15 are pending and under examination.
Action Summary
The objections to claims 6, 7, and 10 are withdrawn.
The prior specification objections are withdrawn in view of the substitute specification and Applicant’s corrections.
The prior art rejection of claims 1-11 under 35 U.S.C. § 112(b) is withdrawn because the amendments clarify the yNIS relationship, define a-d as polynomial coefficients, correct the pH 8.0 coefficient, define the stability period and temperature, and clarify the ionic-surfactant alternatives.
The rejection of claims 1-11 under 35 U.S.C. §112(a) Written Description and enablement rejection is maintained but modified and revisited in view of the amendments to claims 1 and 2.
Modified and Revisited rejection
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1 and 2 now require rifampicin. Accordingly, the prior rationale directed to lack of representative support for rifabutin, rifapentine, and rifaximin is withdrawn. The rejection is maintained in modified form based on the breadth of the claimed rifampicin formulation space.
Claim 1 broadly encompasses rifampicin formulations over pH 2-12, broad nonionic surfactant concentrations, ionic surfactant-present and ionic surfactant-absent conditions, boric acid, and non-boric acid buffer systems, and the recited polynomial boundaries under conditions 9i) – (iv). The original disclosure provides selected formulation studies and coefficient relationships using particular combinations of rifampicin, Tween 80/polysrubate 80, EDTA, benzalkonium chloride, NaCl, boric acid/borax, and boric acid/NaOH. The disclosure does not reasonably demonstrate possession of the substantially broader combinations of pH, buffer identity, surfactant state, and concentration encompassed by claim 1.
The original paragraph [0080] expressly supports the amended stability limitation of at least two hours at 0oC to 40oC; that amendment is therefore not relied upon as a written-description deficiency.
Claim 2 likewise encompasses broad A1/A2 formulation alternatives beyond the representative working formulations. Claims 6, and 10-11 additionally encompass a broad genus of ocular diseases and conditions, whereas the disclosure primarily provides ocular-delivery and selected retinal-neovascularization data. Claims 3-5, 7-9, and new claims 12-15 do not cure the inherited full scope of written description deficiency. The specification does not provide representative therapeutic examples, mechanistic data, or sufficient correlation demonstrating treatment of retinal detachment, neoplasm, tissue fibrosis, or the full breadth of the recited disease genus.
Although the claims encompass formulations having pH values from 2-12, the specification provides coefficient tables and experimental data only for selected pH values approximately between pH 3 and pH 8. The specification therefore does not reasonably demonstrate possession of formula that satisfies the claimed mathematical relationships and the claimed (A1) and (A2) throughout the entire claimed pH range, particularly at pH 2 and pH 9-12.
Furthermore, the claims broadly encompass multiple formulation permutations including formulation containing ionic surfactants, formulations lacking ionic surfactants, nonionic surfactants, boric acid buffer systems, non-boric acid buffer systems, and broad surfactant concentration ranges. However, the specification provides only limited representative examples utilizing selected conditions such as pH 3.32 to pH 8.7 and selected excipients such as benzalkonium chloride, boric acid-NaOH, boric acid-borax, EDTA, Tween 80, and NaCl at specific concentrations. The specification therefore fails to reasonably convey possession of the full breadth of the claimed formulation genus and the generalized mathematical and A1 and A2 relationships recited therein.
Accordingly, the specification fails to reasonably convey to one of ordinary skill in the art that Applicant had possession of the full scope of the claimed invention at the time of filing.
Applicant’s arguments and Response to Amendments
Acknowledgement is made of the receipt and entry of Applicant’s arguments/remarks filed on August 19, 2026.
Applicants’ arguments concerning the written-description rejection have been fully considered but are not fully persuasive.
The Examiner acknowledges that the amendment limiting the claims to rifampicin addresses the previously identified concern regarding possession of the broader rifampicin genus; accordingly, that basis of the rejection is withdrawn. However, the remaining written description deficiency is not whether Applicant possessed particular rifampicin formulation or particular experimentally derived solubility relationships, but whether the original disclosure reasonably conveys possession of the full breadth of the formulation genus now claimed. Although the specification describes and experimentally evaluates selected combinations of rifampicin concentration, nonionic surfactant concentration, pH, buffer systems, and ionic-surfactant conditions and derives solubility boundaries therefrom (see e.g., ¶¶ [081]-[0092] and [0129]-[0157], Tables 9-16_, the claims are not limited to the particular formulation components and systems actually investigated. Rather, they broadly encompass compositions employing nonionic surfactants, buffer systems, ionic-surfactant conditions, and formulation environments beyond the representative species demonstrated to possess the recited dissolution relationships. Accordingly, the disclosure of particular working formulations and empirically derived boundaries does not reasonably convey possession of the full scope of compositions encompassed by the claims, and the written description rejection is maintained as modified.
Modified and Revisited rejection
Claims 1-11 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a topical eye drop formulation comprising rifamycin at an amount of 0.5% by weight, Tween 80 at an amount of 0.5% by weight, EDTA at an amount of 0.1% by weight, benzalkonium chloride at an amount of 0.01% by weight, NaCl at an amount of 0.9% by weight, Boric acid-borax at an amount of 50 mM or boric acid-NAOH at an amount of 100 mM at a pH of 3 to 8 for treating age-related macular degeneration in in rabbit, does not reasonably provide enablement for the full scope of the claimed formulation and the claimed ophthalmic diseases/conditions. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
In determining whether the experimentation required would be undue, the factors set forth in in re Wands, 858 F.2d 731, 737 (Fed. Circ. 1988), have been considered.
The breadth of the claims. Claim 1 encompasses pH values from 2 to 12, 0.0001-50% by weight of nonionic surfactant, multiple ionic-surfactant states, boric and non-boric-acid buffer systems, multiple concentration relationships, and stability over 0-40oC. Claim 2 encompasses broad A1/A2 alternatives. Claims 6 and 10-11 further encompasses numerous ocular diseases and conditions.
Nature and unpredictability. Jindal et al. (Pharm Ind 57, No. 5, 1995) teach that rifamycin degradation varies with pH and buffer systems and report maximum stability around pH 4.0. See Abstract and Results section. Thus, the prior art demonstrates that rifamycin formulation stability is highly sensitive and unpredictable with respect to formulation parameters directly implicated by the instant claims.
Abelson et al (Review of Ophthalmology, published March 3, 2017) teach that pH control effects ophthalmic drug stability and solubility, that ophthalmic formulation commonly maintain about pH 4.75 -7.40, and that excipients including surfactants affect permeability, resistance time, and tolerability. See second paragraph of page 2; See also third paragraph of page 2; second paragraph of page 3. Thus, the prior art demonstrates that ophthalmic formulation behavior is highly dependent on multiple interacting formulation variables, further supporting that substantial experimentation would be required to determine operable formulations throughout the full scope of the claims.
Rodrigues et al. (Pharm Res (2018) 35: 245, pages 1-5) further describes substantial barriers to topical posterior-segment delivery. See Abstract and Section at page 2.
The disclosure itself further demonstrates the empirical and formulation-dependent nature of the claimed dissolution relationship. As explained at paragraphs [0081]-[0089], Applicant determined soluble and insoluble regions by experimentally varying formulation conditions and plotting the resulting pH and nonionic surfactant concentrations to identify boundaries between conditions under which the rifamycin compound remained dissolved and conditions under which the compound was insoluble or precipitated. Paragraph [0090] explains that the graph obtained from these experimental XY-plot values was thereafter generalized using a numerical formula. Paragraph [0092] similarly explains that the relationship between rifamycin concentration and nonionic surfactant concentration in each buffer solution and at each pH may be represented by an approximate relationship, which is expressed as Formula (2).
The later experimental disclosure confirms that Formula (2) represents an empirically derived dissolution boundary rather than universally applicable structural rule for ophthalmic compositions. In Example 9, Applicant varied rifampicin concentration, nonionic surfactant concentration, pH, buffer identity, and ionic surfactant conditions and determined experimentally whether rifampicin remained dissolved. See paragraph [0129]-0131] and Tables 9-12. Paragraph [0136] explains that the resulting data defines a boundary between soluble and insoluble regions and further explains that the soluble state did not change when nonionic surfactant was added to a concentration higher than the experimentally determined boundary. Paragraph [0137] expressly identifies the conditions on the solubility curve and above the curve as the soluble region and the conditions below the curve as the insoluble region. Paragraphs [0139]-[0142] thereafter use those experimentally determined data to predict the nonionic surfactant concentration required for solubilization at a particular rifampicin concentrations and pH values.
Example 10 follows substantially the same empirical procedure for formulations containing 0.00005% or less ionic surfactant or no ionic surfactant. See paragraph [0143]-[0157] and Tables 13-16. Thus, Applicant’s own disclosure demonstrates that determining whether a formulation falls within the soluble region required selection of the actual formulation system, preparation and testing of formulation across multiple formulation variables, observation of dissolution or precipitation, establishment of experimental boundary points, and subsequent mathematical fitting of those experimentally determined boundaries.
Claim 1, however, is not limited to the particular formulation systems from which these empirical relationships were derived. The claim broadly recites “a buffer solution” and “a nonionic surfactant,” together with broad concentration ranges and the functional requirement that rifampicin remain stably dissolved, while encompassing boric and non-boric acid buffer systems and different ionic surfactant conditions. Although the specification provides meaningful guidance and working examples, it does not establish that the recited polynomial relationships constitute universal dissolution relationships applicable, without further empirical determination, to every buffer, nonionic surfactant, ionic surfactant, excipient combination, and formulation environment encompassed by the claim. Accordingly, a skilled artisan seeking to practice the full scope would be required to determine empirically whether materially different formulation systems actually exhibit the claimed stable-dissolution behavior and, where necessary determine the applicable solubility boundary. Such experimentation is not merely routine verification of a predictable result, it is the type of formulation screening used by Applicant itself to identify the operative regions underlying the claimed relationship.
Despite the broad scope of the claims, the specification does not provide sufficient guidance enabling the skilled artisan to determine, without undue experimentation, which combinations of rifamycin species, pH values, surfactant systems, surfactant concentrations, buffer systems, and formulation conditions will satisfy the mathematical relationships in claim 1 and the relation of A1 and A2 in claim 2, and maintain the rifamycin compound “stably dissolved” throughout the full scope of the claims.
With respect to claims 6 and 10-11, the claims broadly encompass topical ophthalmic treatment of numerous posterior ocular disease and conditions including age-related macular degeneration and retinal disorders.
Gil-Martinez et al. (Curr Med Chem. 2020;27(4):583-598) teach that AMD (age-related macular degeneration) treatment remains an evolving and challenging field, and that more clinical trials and safety studies are required in order to achieve an optimal treatment. No effective treatment for treating dry AMD. (See Abstract.) This further supports the unpredictability associated with achieving therapeutic efficacy across the broad scope of the claimed ocular disease treatments.
The state of the art is that the prior art demonstrates that formulation stability and posterior ocular delivery depend on numerous interacting variables including pH, buffer selection, surfactant composition, drug concentration, ocular penetration barriers, and formulation environment. The prior art therefore demonstrates that successful formulation optimization requires careful empirical evaluation and cannot be reliably predicated across the broad formulation genera.
The quantity of experimentation required is high. The quantity of experimentation required to practice the full scope is substantial. Formula (2) provides useful numerical guidance for the particular formulation relationships investigated by Applicant, but does not eliminate the need to determine whether the relationship remains predictive when materially different formulation components encompassed by the claims are employed. Applicant’s own Examples 9 and 10 demonstrate the identification of the soluble region required systematic variation of rifampicin concentration, pH, nonionic surfactant concentration, buffer identity, and ionic surfactant condition, followed by empirical observation of dissolution/precipitation and mathematical approximation of the resulting boundary. A skilled artisan practicing the full breadth of claim 1 would therefore have to perform comparable screening for formulation systems not adequately represented by the disclosed experimental systems in order to determine whether the selected composition satisfies the required stable dissolution result. When considered together with the breadth of the claims, the formulation-sensitive nature of rifampicin solubilization, the limited representativeness of the working examples relative to the claimed genus, and the unpredictability demonstrated by the cited art, the required experimentation is undue rather than merely routine optimization.
Therefore, the specification fails to enable the full scope of the claimed invention.
Applicant’s arguments and Response to Amendments
Acknowledgement is made of the receipt and entry of Applicant’s arguments/remarks filed on August 19, 2026.
Applicants’ arguments concerning the enablement rejection have been fully considered but are not fully persuasive.
The Examiner acknowledges that the amendments narrow the claims to rifampicin, clarify the mathematical relationship between the actional nonionic surfactant concentration and Ynis, define the polynomial coefficients, and provide an objective minimum duration and temperature range for the recited stable dissolution. These amendments clarify the claimed subject matter and narrow certain aspects of the previously claimed scope. Accordingly, the enablement rejection has been reconsidered and modified in view of the amendments.
The amendments, however, do not resolve the scope of enablement deficiency. The issue is not whether the specification teaches particular rifampicin formulations that can be stably dissolved, nor whether the specification provides mathematical relationships derived from particular experimental data. Rather, the issue is whether the disclosure enables a person of ordinary skill in the art to make and use substantially the full scope of the compositions encompassed by the claims without undue experimentation.
Applicant’s own disclosure demonstrates that the recited mathematical relationships were obtained from empirical formulation studies. Paragraphs [0081]-[0092] describe experimentally identifying soluble and insoluble regions and mathematically approximating the boundaries therebetween. Examples 9 and 10 likewise vary rifampicin concentration, pH, buffer system, nonionic surfactant concentration, and ionic-surfactant condition and experimentally determine whether dissolution is maintained before deriving the corresponding solubility curves and equations. See paragraphs [0129]-0157] and Tables 9-16. Paragraph [0137], for example, expressly explains that conditions on and above the experimentally determined curve constitute the soluble region, whereas conditions below the curve constitute the insoluble region.
Thus, Formula (2) is useful guidance concerning an empirically determined dissolution boundary, but Applicant has not established that the disclosed predictive rule for every formulation encompassed by the claims irrespective of the actual identities and interactions of the broadly recited formulation components. Claim 1 is not restricted to the particular buffers, nonionic surfactants, ionic surfactant conditions, and formulation environments used to derive the disclosed experimental relationships. Consequently, for materially different formulation systems encompassed by the claim, a skilled artisan would still be required to determine composition falls within an operative soluble region and maintains rifampicin in the claimed stably dissolved state.
Nor the rejection based merely on the proposition that some experimentation is required. But rather, when the Wands factors are considered together, the breadth of the claimed formulation genus, the formulation-dependent nature of rifampicn solubilization, the empirical manner in which Applicant itself determined the operative dissolution boundaries, the limited representativeness of the disclosed working formulations relative to the full claimed scope, and the predictability evidenced by the cited art establish that the amount of experimentation required to identify operative formulations throughout substantially the full scope would be undue. Applicant’s amendments therefore do not overcome the enablement rejection, which is maintained and modified.
New Rejection necessitated by claim amendment
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 15 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 15 depends from claim 1 and recites pH “greater than 8.5,” while claim 1 limits pH to 2-12. Because claim 15 recites no upper boundary, it encompasses pH values greater than 12 and therefore does not, as written, further limit 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.
Modified and Revisited rejection
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.
(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.
Claims 1-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Serizawa (US2017/0202850 A1).
Serizawa teaches an ophthalmic composition comprising an effective amount of rifamycin compound selected from the group consisting of rifampicin, rifabutin, rifapentine and rifaximin, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier., wherein the pharmaceutically acceptable carrier comprises a tonicity adjusting agent, wherein the tonicity adjusting agent is saline, dextrose, glycerin, aqueous potassium chloride, buffer salts, propylene glycol, or mannitol, and the ophthalmic composition of claim 10 in the form of a topical eye drop. (See claims 9-12.) Moreover, Serizawa teaches the ophthalmic composition is for use in the manufacture of a medicament for treatment of an ocular disease, disorder or condition. 14, wherein the ocular disease, disorder or condition is selected from age related macular degeneration (AMD), ocular neovascularization, retinal ganglion cell injury and brain damage. (See claims 13-14.)
Particular preference is expressly given to the following formulations of the Tables 1, 2, and 3:
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422
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304
636
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146
618
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612
858
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The instant specification refers to nonionic surfactant to include Tween 80 and benzalkonium chloride (see specification at paragraph [0061]. The ionic surfactant disclosed in the specification at paragraph [0071] encompasses benzalkonium chloride.
Serizawa Tables 1-3 expressly disclose ophthalmic rifamycin formulations containing Tween 80 at 0.5%, which is considered by weight because paragraph [0062] of Serizawa teaches wt%, corresponds to the claimed nonionic surfactant concentration range of 0.00001% to 50% by weight and benzalkonium chloride at 0.01%.
Under one reasonable interpretation, benzalkonium chloride functions as a preservative component in the disclosed formulations. (See instant specification at paragraph [0071].) Under such interpretation, the Serizawa formulations satisfy claim condition (iv), which recite formulation comprising 0.00005% or less ionic surfactant or formulations not comprising such ionic surfactant as the benzalkonium chloride is a preservative, rendering the formulations of Serizawa free of ionic surfactant.
Alternatively, Applicant’s own specification identifies benzalkonium chloride as an ionic surfactant. (See specification at paragraph [0061].) Under Applicant’s own characterization, the Serizawa formulations comprise greater than 0.00005% ionic surfactant and therefore satisfies (ii) of claim 1.
The mathematical expression of previously disclosed concentration relationships does not render the claimed compositions patentably distinct from the prior art compositions expressly disclosed by Serizawa.
Serizawa further expressly teaches rifamycin was completely dissolved at room temperature in the eye drop formulations of Example 1A and Examples 5A-8A in Tables 1 and 2, and in Examples 11A and 12A for weeks. Additionally, rifamycin was also completely dissolved at refrigerated temperature in the eye drop formulation of Examples 13A -16A for more than several weeks. (See paragraphs [0087] to [0089]). The amendment requirement of stable dissolution for at least two hours at 0oC to 40oC does not distinguish the claimed subject matter from Serizawa’s expressly stable room- and refrigerated temperature formulations. Serizawa expressly reports complete dissolution at room and refrigerated temperatures and absence of precipitation for weeks in the relied-upon formulations. Room and refrigerated temperatures fall within 0-40oC range, and a formulation remains dissolved for weeks necessarily remained dissolved for at least two hours.
For amended claim 1, Serizawa discloses 0.5 wt% Tween 80, within the claimed nonionic surfactant range. Under the instant specification’s characterization of benzalkonium chloride as an ionic surfactant, Serizawa’s 0.01 wt% benzalkonium chloride is greater than 0.00005 wt% and maps to condition (ii). Under the alternative preservative characterization, the boric acid formulation falls within condition (iv). The mathematical expression of concentration relationship associated with the same disclosed formulation does not create a structurally different composition.
For claim 2, Serizawa teaches formulations on Table 2 comprising 0.5 -1% by weight rifamycin, 0.5% by weight Tween 80 (nonionic surfactant), 0.01% by weight benzalkonium chloride (an ionic surfactant according to the instant spec.), and pH 8.5 to 8.7, satisfying (A2) of claim 2. Claims 3-5 are met by Serizawa’s carrier and tonicity agent disclosures; claim 6 and 10-11 by its express ocular-treatment/medicament teachings; claim 7 by its buffering agent, antioxidant and preservative disclosures; claim 8 by rifampicin; and claim 9 by the 0.25%, 0.5% and 1% by weight rifampicin examples.
New claim 12 is anticipated because Tables 1-3 contain EDTA and benzalkonium chloride. New claim 13 is anticipated because Serizawa ¶ [0062] identifies sorbitan ether esters of oleic acid, including polysorbate/Tween surfactants. New claim 14 is anticipated at least by its boric-acid alternative because Serizawa Tables 1-3 use boric acid-borax and boric acid-NaOH buffers. Accordingly, Serizawa teaches each and every limitation of claims 1-14 and anticipated the claims.
Applicant’s arguments and Response to Amendments
Acknowledgement is made of the receipt and entry of Applicant’s arguments/remarks filed on August 19, 2026.
Applicants’ arguments concerning the anticipation rejection have been fully considered but are not fully persuasive.
Applicant’s argument that Serizawa fails to expressly or inherently disclose the claimed formulation conditions is not persuasive. The rejection does not rely upon the possibility that an arbitrary Serizawa formulation may satisfy the claimed dissolution relationship. Rather, Serizawa expressly discloses the same rifampicin ophthalmic formulation condition relied upon herein and further experimentally demonstrates that rifampicin was completely dissolved in those formulations and did not precipitate for weeks. See Tables 1-3; ¶¶[0087]-[0089]. The instant specification explains that Formula (2) represents an empirically derived relationship between rifampicin concentration and nonionic surfactant concentration and nonionic-surfactant concentration defining the boundary for dissolution, and that formulation conditions on or above the solubility boundary constitute the soluble region. Thus, the subsequently expressly mathematical characterization does not impart patentable distinction to a prior-art composition already possesses the claimed formulation characteristics and exhibits the claimed dissolution behavior.
Moreover, Applicant’s amendment requiring the rifampicin be “stably dissolved … for at least two ours at temperature of 0oC to 40oC” does not distinguish over Serizawa. Serizawa expressly reports complete dissolution at room temperature and refrigerated temperature and absence of precipitation for weeks in the relied-upon formulations. Room- and refrigerated temperatures fall within the claimed 0oC – 40oC range, and a formulation remained dissolved for weeks necessarily remains dissolved for at least two hours.
New rejection necessitated by claim amendment
Claim Rejections - 35 USC § 103
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 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.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Serizawa (US2017/0202850 A1) as applied to claims 1-14.
Serizawa teaches the subject matter of claim 1 and further teaches ophthalmic composition at alkaline pH values extending above 8.5, including pH ranges of 7-8.5, 7.5-9.0, and 7.5-12. See ¶[0011].
It would have been obvious to one of ordinary skill in the art to select a pH greater than 8.5, but within the pH 2-12 range of claim 1, from Serizawa’s expressly disclosed alkaline ranges in order to obtain an ophthalmic acceptable rifampicin formulation having desired solubility and stability. Serazawa identifies pH as a formulation parameter and teaches overlapping alkaline ranges. Selection of a value within the disclosed overlapping range would have been routine selection/optimization of a known-result effective variable.
Modified and Revisited rejection
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 1-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,850,213 B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
The U.S. patent claims teach a method of treating an ocular disease, disorder or condition which results from ocular neovascularization comprising topically administering to a patient in need thereof a stable ophthalmic composition comprising about 0.01 wt % to 10 wt % of a solubilized rifamycin compound selected from rifampicin, rifabutin, rifapentine, rifaximin, or a pharmaceutically acceptable salt thereof, about 0.1 wt % to 50 wt % of a non-ionic surfactant, and a pH of about 2 to 12, wherein the composition does not comprise 0.1 wt % rifampicin in combination with 2 wt % polysorbate 80 (Tween 80) wherein the pH is buffered with a citrate, a phosphate, a bicarbonate, a sodium salt, potassium, acetic acid, citric acid, lactic acid, phosphoric acid, hydrochloric acid, sodium hydroxide, sodium phosphate, sodium citrate, sodium acetate, sodium lactate, citrate/dextrose, sodium bicarbonate, ammonium chloride, or a combination thereof, wherein the composition is stable for at least one day, and wherein the ocular neovascularization comprises retinal or choroidal neovascularization. (See claims 1 and 2.) The U.S. patent claims further teach the composition is a topical eye drop and further comprising a pharmaceutically acceptable carrier, wherein the pharmaceutically acceptable carrier comprises a tonicity adjusting agent, wherein the tonicity adjusting agent is selected from the group consisting of saline, dextrose, glycerin, aqueous potassium chloride, buffer salts, propylene glycol, and mannitol. (See claims 12-14.) A second claim set recites stable ophthalmic compositions with borate buffer.
The instant requirement that rifampicin remain stably dissolved for at least two hours at 0oC to 40oC does not establish patentable distinctness over the patent stable rifampicin compositions requiring at least one day of stability. The polynomial limitations characterize concentration/pH relationships within the same stable rifampicin ophthalmic formulation space. Selection of rifampicin, particular surfactant/buffer conditions, and mathematical characterization of the resulting stable formulation would have been obvious variation of the patented subject matter.
Claims 3-5 and 7-9 add carriers, tonicity agents, excipients, rifampicin and concentration limitations expressly or obvious from the U.S. patent claims. Claims 6 and 10-11 substantially overlap the ocular-treatment subject matter of the patent claims. Claims 12-14 add formulation components disclosed in the common formulation platform, and claim 15 selects pH above 8.5 from the broader patented pH 2-12 range. Accordingly, claims 1-15 are not patentably distinct from the U.S. patent claims.
Applicant’s arguments and Response to Amendments
Acknowledgement is made of the receipt and entry of Applicant’s arguments/remarks filed on August 19, 2026.
Applicants’ arguments concerning the nonstatutory double patenting rejection have been considered. The rejection is revised to expressly address the stability and mathematical limitations and explain why the instant claims represent obvious variation of the stable rifampicin ophthalmic compositions in the U.S. patent No. 11,850,213.
Conclusion
Claims 1-15 are not allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JEAN P CORNET/Primary Examiner, Art Unit 1628
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