DETAILED ACTION
Claim Status
As of the Non-Final Office Action mailed 11/18/2025, claims 1, 20, 24-28, 30-32, 48 and 50-52 were pending.
In Applicant's Response filed on 2/17/2026, claims 1, 24, and 48 were amended.
As such, claims 1, 20, 24-28, 30-32, 48 and 50-52 are pending and have been examined herein.
Withdrawn Objections/Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in this application. Any objections or rejections not specifically reiterated are hereby withdrawn.
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(s) 1, 20, 24-28, 30-32, 48, and 50-52 remain rejected under 35 U.S.C. 103 as being unpatentable over de los Pinos et al (US 2016/0228568 A1, 18 September 2014; Published 11 Aug 2016; previously cited) as evidenced by PubChem (“Irdye 700 DX” Compound Summary; Accessed from the Internet 6 Jan 2025; Retrieved from https://pubchem.ncbi.nlm.nih.gov/compound/Irdye-700DX; previously cited) in view of Ostrow et al (US 10,076,515 B2, 27 July 2017; published 18 September 2018; previously cited) and Hecht et al (US 5,578,578 A, 19 April 1995; Published 26 Nov 1996; previously cited).
De los Pinos teaches methods and compositions for the diagnosis and treatment of tumors, such as ocular tumors, using virus-like particles conjugated to photosensitive molecules (abstract and see claim 1 of de los Pinos) (“virus-like particle conjugates comprising (a) photosensitive molecules and (b) VLPs, wherein the photosensitive molecules are conjugated to . . . a VLP” as in instant claim 1 in-part and 48 in-part). The capsid proteins are papilloma virus capsid proteins such as human papilloma virus capsid proteins, and the capsid proteins comprise L1 or a combination of L1 and L2 capsid proteins (see claims 2, and 5-7 of de los Pinos) (“wherein the VLP comprises papillomavirus capsid proteins” as in instant claim 30; “wherein the papillomavirus capsid proteins are human papillomavirus capsid proteins” as in instant claim 31; “wherein the papillomavirus capsid proteins comprise L1 capsid proteins . . . or a combination of L1 and L2 capsid proteins” as in instant claim 32). The photosensitive molecules are covalently conjugated to the capsid proteins (see claim 10 of de los Pinos) (“wherein the photosensitive molecules are conjugated to capsid proteins of a VLP” as in instant claim 1 in-part, 48 in-part, and 53 in-part). The reference also teaches that photosensitive molecules are activated by infrared or near-infrared light (see claim 38 of de los Pinos), such as a phthalocyanine dye (see claim 39 of de los Pinos), where the phthalocyanine dye is IRDye 700DX (para 0022) (“wherein the photosensitive molecules comprise dye molecules” as in instant claim 25; “wherein the dye molecules comprise phthalocyanine dye molecules” as in instant claim 26). The reference also teaches that reagents such as MgCl2, trehalose (also a protective excipient as in working example 1 of the instant specification), polysorbate 20, or polysorbate 80 (also a surfactant) can be used singularly or in combination to deliver the virus-like particles (para 0088) and the photosensitive virus-like particles are provided in a sterile, saline solution that can also include NaCl (para 0098). The virus-like particles comprise about 10 to about 1000 photosensitive molecules (see claim 79 of de los Pinos) or about 50 to about 500 photosensitive molecules (para 0006) (“wherein the VLPs comprise 100-500 of the photosensitive molecules” as in instant claims 28 and 51).
De los Pinos does not explicitly teach that the composition contains “0.01% to 0.5% VLP drug conjugate” as recited in instant claim 20, “0.04% VLP drug conjugate” and “5% trehalose dihydrate” as in instant claim 24 or “1% to 10% trehalose dihydrate” as in instant claim 50 in-part. However, it would have been a matter of routine experimentation using standard laboratory techniques available at the time of filing to determine the optimal concentration of VLP drug conjugate and trehalose dihydrate for use in the composition taught by de los Pinos with a reasonable expectation of success. Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Furthermore, while de los Pinos does not explicitly teach that the “VLP drug conjugates are in suspension” as in instant claim 1 in-part, the reference teaches that the VLP conjugates can be administered intra-ocularly via injection (see claims 61-63 of de los Pinos), which would necessarily require the VLP to be in a suspended solution. Thus, a solution of VLP drug conjugates in suspension would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date.
Evidentiary reference PubChem shows the chemical structure (shown below) for IRDye 700DX, which has the chemical formula of C74H96N12Na4O27S6Si3 (see p. 1 of PubChem). Thus, the phthalocyanine dye IRDye 700DX as taught in de los Pinos renders “wherein the photosensitive molecules comprise the following compound” and chemical structure as in instant claim 27 and instant claim 52 prima facie obvious.
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Figure 1: Chemical Structure of IRDye 700DX
De los Pinos differs from the instantly claimed invention in that it does not teach that the composition has an isotonicity of 255-345 mOsm/L (related to instant claims 1 in-part, 48 in-part, and 53 in-part) and a low salt concentration of 0.2% to 0.6% (related to instant claim 1 in-part) or NaCL concentration of 0.2 to 0.6% (related to instant claim 48 in-part).
Ostrow teaches an ophthalmic composition for treatment of an ophthalmic disorder or condition (abstract). The reference teaches that the composition is formulated to not disrupt the ionic balance of the eye by having an deliverable osmolarity of about 250 to about 350 mOsm/L (see “Osmolarity” para 1 and 3). An osmolarity of about 250 to about 350 mOsm/L overlaps with the instantly claimed 255-345 mOsm/L. MPEP 2144.05 states that in cases where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990), MPEP 2144.05). Thus, about 250 to about 350 mOsm/L renders prima facie obvious “the composition has an isotonicity of 255-345 mOsm/L” as in instant claim 1 in-part and 48 in-part. The reference also teaches that the composition contains organic buffering agents such as 2-(N-morpholino)ethanesulfonic acid (MES) (col 18, lines 21-23) (“2-(N-morpholino)ethanesulfonic acid (MES)” as in instant claim 1 in-part) and tonicity adjusting agents that reduce local irritation by preventing osmotic shock, such as magnesium chloride, sodium chloride in amounts of 0.5% to about 2% (col 18 lines 48-50, 59-61; col 19 line 3) (overlaps with “wherein the composition comprises 0.1% to 1.0% MES” as in instant claim 1 in-part, “0.43% MES” and “0.37% sodium chloride” as in instant claim 24; “0.2% magnesium chloride” as in instant claim 24; and “0.5% magnesium chloride” as in instant claim 50 in-part; overlaps with “salt concentration of 0.2% to 0.6%” as in instant claim 1 in-part). Co-surfactants such as polysorbate 80, which maintains optimal pD/pH for stability, can be present in amounts of 0.1% to 20% (col 31 lines 45-59, col 32 lines 14-19) (“0.1% PS80” as in instant claim 50 in-part).
Ostrow does not explicitly teach that the composition contains 0.05% polysorbate 80 as instantly claimed in claim 24. However, it would have been a matter of routine experimentation using standard laboratory techniques available at the time of filing to determine the optimal concentration of polysorbate for use in the composition taught by Ostrow with a reasonable expectation of success. Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Finally, Hecht teaches ophthalmic solutions that are physiologically compatible (abstract). The reference teaches that a physiologically compatible salt solution has a pH of 6.8 and an osmolality of between 250 and 350 mOsm/L (col 4, lines 60-62). The table present in col 5 of the reference teaches that sodium chloride can be present in an amount of 0.01 to 1.0 wt %. This amount overlaps with the instantly claimed “and a low salt concentration of 0.2% to 0.6%” as in instant claim 1 in-part and “0.2% to 0.6% sodium chloride” as in instant claim 48 in-part. This shows that a low salt can be used in an ophthalmic solution and remains physiologically compatible.
Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to create a composition for treating tumors in the eye containing virus-like particles and photosensitive molecules as taught by de los Pinos, where the composition has an isotonicity of about 250 to about 350 mOsm/L as taught by Ostrow, to arrive at the instantly claimed invention. As Ostrow shows an ophthalmic deliverable composition can contain MES, tonicity adjusting agents (magnesium chloride and sodium chloride), and polysorbate 80, one of ordinary skill would have been motivated to modify the composition de los Pinos to include the instantly claimed components in the instantly claimed concentrations as taught by Ostrow with a reasonable expectation of advantageously having a composition that is formulated to not disrupt the ionic balance of the eye, reduce local irritation by preventing osmotic shock, and which maintains optimal pD/pH for stability as taught by the prior art.
It also would have been obvious prior to the effective filing date of the instantly claimed invention to create a composition for treating tumors in the eye containing virus-like particles and photosensitive molecules as taught by de los Pinos, where the composition has a low salt concentration as taught by Hecht, to arrive at the instantly claimed invention. As Hecht shows that ophthalmic solution can have a low sodium concentration, one of ordinary skill would have been motivated to modify the composition as taught by de los Pinos to include a low sodium concentration with a reasonable expectation of advantageously having an ophthalmic solution that maintains physiological compatibility, a pH of 6.8, and osmolarity of between 250 and 350 mOsm/L as taught by the prior art.
Response to Arguments
Applicant’s arguments in the Remarks filed 2/17/2026 have been fully considered but are not persuasive.
Analogous Art Arguments
On p. 6-10 of Remarks, Applicant argues that the Ostrow and Hecht references are not analogous art because they are purportedly neither in the same field of endeavor as the instant invention and address different technical problems. In response, the examiner disagrees. There is no requirement for references to be both in the same field of endeavor and reasonably pertinent to classify as analogous prior art. A reference is analogous art to the claimed invention if: (1) the reference is from the same field of endeavor as the claimed invention (even if it addresses a different problem); or (2) the reference is reasonably pertinent to the problem faced by the inventor (even if it is not in the same field of endeavor as the claimed invention). Note that "same field of endeavor" and "reasonably pertinent" are two separate tests for establishing analogous art; it is not necessary for a reference to fulfill both tests in order to qualify as analogous art. See Bigio, 381 F.3d at 1325, 72 USPQ2d at 1212. While the examiner considers "explanations of the invention’s subject matter in the patent application, including the embodiments, function, and structure of the claimed invention" (see Airbus S.A.S. v. Firepass Corp., 941 F.3d 1374, 1380, 2019 USPQ2d 430083 (Fed. Cir. 2019)), the examiner also considers the disclosure of each reference "in view of the ‘the reality of the circumstances,’" weighed "from the vantage point of the common sense likely to be exerted by one of ordinary skill in the art in assessing the scope of the endeavor." Airbus, 41 F.3d at 1380. See also Donner Technology, LLC v. Pro Stage Gear, LLC, 979 F.3d 1353, 2020 USPQ2d 11335 (Fed. Cir. 2020); Sanofi-Aventis, 66 F.4th at 1378; and Netflix, Inc. v. DivX, LLC, 80 F.4th 1352, 1358-59, 2023 USPQ2d 1057 (Fed. Cir. 2023). Importantly, "The field of endeavor is ‘not limited to the specific point of novelty, the narrowest possible conception of the field, or the particular focus within a given field.’" Netflix (quoting Unwired Planet, LLC v. Google Inc., 841 F.3d 995, 1001, 120 USPQ2d 1593, 1597 (Fed. Cir. 2016)). One of ordinary skill in the art, applying common sense, would limit themselves merely to the field of ophthalmic biotherapeutic formulations as argued; rather one of ordinary skill would also reasonably look to prior art related to general ophthalmic formulations/solutions when determining what encompasses relevant field(s) of endeavors (i.e., nature of the invention broadly). Both Ostrow and Hecht concern themselves with ophthalmic solutions/formulations and, thus, are in the same field of endeavor.
Regarding "reasonably pertinent," Applicant argues, in sum, that the problem faced by the inventors is preventing aggregation, and that Ostrow and Hecht do not provide guidance on preventing protein aggregation, maintaining quaternary structure of large macromolecules, or ensuring biotherapeutic stability. However, the examiner reiterates that the references do not need to be both in the same field of endeavor and reasonably pertinent to classify as analogous prior art. Moreover, Applicant ignores the explicit disclosure of Ostrow related to anti-aggregation additives. Specifically, column 30 lines 59-67 and column 31 lines 1-7 states "Additional useful stabilization agents for ophthalmically acceptable formulations include one or more anti-aggregation additives to enhance stability of ophthalmic formulations by reducing the rate of protein aggregation. The anti-aggregation additive selected depends upon the nature of the conditions to which the ophthalmic agents, . . ., are exposed. For example, certain formulations undergoing agitation and thermal stress require a different anti-aggregation additive than a formulation undergoing lyophilization and reconstitution. Useful anti-aggregation additives include, by way of example only, urea, guanidinium chloride, simple amino acids such as glycine or arginine, sugars, polyalcohols, polysorbates, polymers such as polyethylene glycol and dextrans, alkyl saccharides, such as alkyl glycoside, and surfactants." The examiner notes that polysorbate 80 is required by the instant claims as well (i.e., would also operate as an anti-aggregation additive based on the teachings of Ostrow). Thus, for at least these reasons, Ostrow and Hecht apply as analogous art.
Impermissible Hindsight Argument and Reasonable Expectation to Combine
Applicant argues that the use of the Ostrow reference to teach MES as a buffer in an ophthalmic solution relies on impermissible hindsight. Applicant argues that Ostrow does not teach MES as a preferred buffer and discloses a purportedly broad genus of buffers. Applicant argues in sum that, given that Ostrow does not indicate preference, suitability for particular application, or advantages of other disclosed buffers, there is no motivation to select MES specifically for VLP formulations.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In essence, Applicant is arguing that the combination of at least de los Pinos and Ostrow is “hindsight” because “express” motivation to specifically use MES in the reference is lacking. However, there is no requirement that an "express, written motivation to combine must appear in prior art references before a finding of obviousness." Ruiz v. A.B. Chance Co., 357 F.3d 1270, 1276, 69 USPQ2d 1686, 1690 (Fed. Cir. 2004). One of ordinary skill in the art, looking to at least the Ostrow reference would find that they were free to choose from buffers as described by Ostrow for the purpose of “aqueous solution stability” and to act as a tonicity adjusting agent to maintain the ophthalmic at a particular pD and ion concentration.
Applicant also argues that the examiner's reasonable expectation of success argument purportedly mischaracterizes the problem to be solved and the function of MES in the claimed invention. Applicant argues that the problem of preventing aggregation and precipitation while simultaneously maintaining ophthalmic compatibility was not contemplated by the prior art and that the prior art provides no basis for expecting MES to solve the problem of aggregation to one of ordinary skill in the art. Applicant argues that the selection of MES, and the discovery that MES specifically prevents VLP precipitation is an unexpected result that defeats obviousness. Applicant also argues that “routine optimization” rationale is insufficient.
In response, the examiner disagrees. Applicant is arguing what essentially constitutes an additional property of MES as the source of unexpected results. Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). Furthermore, Applicant's purported reason for the utilization of MES need not be the same as the prior art, particularly given that the claims are drawn to a composition and not, for example, a method for preventing protein aggregation in an ophthalmic composition containing VLP conjugates. Simply put, the prior art just needs provides a reasonable teaching, suggestion, or motivation for the inclusion of MES in an ophthalmic solution not Applicant's (such as Ostrow teaching pH stabilization and physiological compatibility when using MES). Furthermore, Applicant’s arguments regarding routine optimization is misplaced. The examiner did not state that the selection of MES was a result of routine optimization; rather that rationale was applied to the criticality of the concentrations of VLP drug conjugate and trehalose dihydrate as claimed. Applicant has yet to provide any empirical evidence showing the criticality of the concentrations claimed in the instant composition. As such, absent evidence to the contrary, the workable ranges/concentrations are a matter of routine experimentation that can be undertaken by one of ordinary skill in the art before the effective filing date of the instant invention.
Unexpected Results
Applicant argues that the MES-containing formulation exhibit unexpectedly superior VLP stability and elimination of precipitation. Applicant supports this contention with working example 1 of the instant specification comparing formulations containing (1) potassium phosphate buffer and NaCl (control), (2) potassium phosphate buffer, trehalose dihydrate, magnesium chloride, sodium chloride, and PS80 at pH 7 (formula A), (3) HEPES (i.e., a Good’s buffer), trehalose dihydrate, magnesium chloride, PS80 at pH 7.5 (formula B), and (4) MES (a Good’s buffer), trehalose dihydrate, magnesium chloride, and PS80 at pH 6.5. Applicant states that the specification shows that the formulations containing MES (as well as HEPES) had no precipitation, while the control and formulation containing potassium phosphate had precipitation. Applicant further argues Ostrow’s disclosure of phosphate buffering agents would lead one of ordinary skill to select a phosphate buffer because phosphate buffers are purportedly the most common pharmaceutical buffers and Ostrow presents them as a suitable option alongside MES. Applicant states that the instant specification shows the MES is superior over phosphate buffers in the instantly claimed composition. Applicant contends that Ostrow treats all disclosed buffers as functionally equivalent alternatives for achieving ophthalmic compatibility with no teaching that buffer identity would affect protein aggregation, de los Pinos is silent to the use of buffers, and that one of ordinary skill in the art would have no reason to expect MES to outperform phosphate and VLP stability.
In response, the examiner notes that, as per MPEP § 716.02, [a]ny differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). "A greater than expected result is an evidentiary factor pertinent to the legal conclusion of obviousness ... of the claims at issue." In re Corkill, 771 F.2d 1496, 226 USPQ 1005 (Fed. Cir. 1985). However, a greater than additive effect is not necessarily sufficient to overcome a prima facie case of obviousness because such an effect can either be expected or unexpected. Applicants must further show that the results were greater than those which would have been expected from the prior art to an unobvious extent, and that the results are of a significant, practical advantage. Ex parte The NutraSweet Co., 19 USPQ2d 1586 (Bd. Pat. App. & Inter. 1991) (see MPEP § 716.02(a)). In this case, did the prior art, prior to the effective filing date, recognize MES’ ability to lower/reduce protein aggregation? Solely to rebut Applicant's argument, the examiner provides Kameoka et al (J Biochem. 2007 Sep;142(3):383-91. doi: 10.1093/jb/mvm145. Epub 2007 Jul 23), which discusses the effect of buffer species on unfolding and aggregation of humanized IgG (title). The aggregation propensity of humanized antibody after heat treatment was evaluated in the presence of six buffer species. The comparison under equivalent pH showed high aggregation propensity on phosphate and citrate buffer. In contrast, 2-(N-Morpholino) ethane sulfonate (MES), 3-(N-Morpholino) propane sulfonate (MOPS), acetate and imidazole buffer showed lower aggregation propensity than the above two buffers. Meanwhile, unfolding temperature evaluated by differential scanning calorimetry measurement was not altered among these buffer species. The light scattering analysis suggested that heat-denatured intermediate was aggregated slightly on MES and acetate buffer. Therefore, it was found that the different aggregation propensity among buffer species was caused from the aggregation propensity of heat-denatured intermediate rather than the unfolding temperature. Furthermore, it was revealed that the aggregation dependency on buffer species is accounted for by the specific molecular interaction between buffer and IgG, rather than the ionic strength. On the contrary, on the analyses of unfolding and aggregation propensity by molecular dissection of IgG into Fab and Fc fragments, aggregation propensity of Fc fragment on MES, acetate and phosphate buffer was almost the same as whole IgG. From the above results, it was suggested that the specific interaction between buffer molecule and Fc domain of IgG was involved in the aggregation propensity of heat-denatured IgG. Thus, Applicant’s arguments are not persuasive and the rejection is maintained.
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.
Rejection 1
Claims 1, 25-26, 28, and 30-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5, 13, 16-19 of U.S. Patent No. 10,117,947 B2 (referenced herein as ‘947; commonly owned) in view of Ostrow et al (US 10,076,515 B2, 27 July 2017; published 18 September 2018) and Hecht et al (US 5,578,578 A, 19 April 1995; Published 26 Nov 1996). Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed tumor-targeting virus-like particle and method of ‘947 necessarily requires the instantly claimed composition and would read on the instant claims if it were available as prior art.
Patented claim 1 of ‘947 recites, “a tumor-targeting papilloma virus-like particle comprising about 50 to about 500 near infrared phthalocyanine dye molecules conjugated to papilloma virus capsid proteins.” This reads on “a virus-like particle (VLP) drug conjugates comprising (a)photosensitive molecules and (b) VLPs, wherein the photosensitive molecules are conjugated to capsid proteins of a VLP” as in instant claim 1 in-part, “wherein the photosensitive molecules comprise dye molecules” as in instant claim 25, “wherein the dye molecules comprise phthalocyanine dye molecules” as in instant claim 26, “wherein the VLPs comprise 10-1000 photosensitive molecules” as in instant claim 28, and “wherein the VLP comprises papillomavirus capsid proteins” as in instant claim 30.
Patented claim 3 of ‘947 recites “wherein the papilloma virus-like particle comprises human papilloma virus (HPV) L1 capsid proteins”, which reads on “wherein the papillomavirus capsid proteins are human papillomavirus capsid proteins” as in instant claim 31 and “wherein the papillomavirus capsid proteins comprise L1 capsid proteins” as in instant claim 32.
Patented claim 5 of ‘947 recites “wherein the modified HPV L1 capsid proteins comprise a combination of modified HPV L1 capsid proteins and wild-type HPV L2 capsid protein”, which reads on “wherein the papillomavirus capsid proteins comprise . . . a combination of L1 and L2 capsid proteins” as in instant claim 32.
Patented claim 13 of ‘947 recites “administering, to a subject having an ocular tumor, a tumor-targeting papilloma virus-like particle comprising about 50 to about 1000 photosensitive molecules that become toxic or produce a toxic molecule upon light activation” which reads on “” as in instant claim 1 in-part and “wherein the VLPs comprise 10-1000 photosensitive molecules” as in instant claim 28.
Patented claim 16 of ‘947 recites, “wherein the near infrared phthalocyanine dye molecules comprise IR700 dye molecules conjugated to capsid proteins”, claim 17 of ‘947 recites “comprising about 200 near infrared phthalocyanine dye molecules”, claim 18 of ‘947 recites “comprising about 300 near infrared phthalocyanine dye molecules”, and claim 19 of ‘947 recites “comprising about 400 near infrared phthalocyanine dye molecules”, which reads on “wherein the phthalocyanine dye molecules comprise the chemical formula C74H96N12Na4O27S6Si3 and dye structure” as in instant claim 27 (i.e., IRDye700DX; see 103 rejection above for chemical formula and structure) and “wherein the VLPs comprise 10-1000 photosensitive molecules” as in instant claim 28.
‘947 differs from the instant application in that it does not teach that the composition has an isotonicity of 255-345 mOsm/L (related to instant claim 1 in-part).
However, Ostrow teaches that ophthalmic compositions can be formulated to not disrupt the ionic balance of the eye by having an deliverable osmolarity of about 250 to about 350 mOsm/L (see “Osmolarity” para 1 and 3). The reference also teaches that the composition contains organic buffering agents such as 2-(N-morpholino)ethanesulfonic acid (MES) (col 18, lines 21-23) (“2-(N-morpholino)ethanesulfonic acid (MES)” as in instant claim 1 in-part) and tonicity adjusting agents that reduce local irritation by preventing osmotic shock, such as magnesium chloride, sodium chloride in amounts of 0.5% to about 2% (col 18 lines 48-50, 59-61; col 19 line 3).
Finally, Hecht teaches ophthalmic solutions that are physiologically compatible have a pH of 6.8 and an osmolality of between 250 and 350 mOsm/L while containing a low salt concentration (col 4, lines 60-62). The table present in col 5 of the reference teaches that sodium chloride can be present in an amount of 0.01 to 1.0 wt %.
Therefore, it would have been obvious for the tumor-targeting papilloma virus-like particle comprising about 50 to about 500 near infrared phthalocyanine dye molecules conjugated to papilloma virus capsid proteins, which is administered to a subject with an ocular tumor as taught by de los Pinos, to have an isotonicity of 255-345 mOsm/L with a reasonable expectation that the composition would not disrupt the isotonic balance of the eye with a reasonable expectation of success as taught by Ostrow.
It also would have been obvious prior to the effective filing date of the instantly claimed invention to create a composition for treating tumors in the eye containing virus-like particles and photosensitive molecules as taught by de los Pinos, where the composition has a low salt concentration as taught by Hecht, with a reasonable expectation of advantageously having an ophthalmic solution that maintains physiological compatibility, a pH of 6.8, and osmolarity of between 250 and 350 mOsm/L as taught by Hecht.
Rejection 2
Claims 1, 25-28, 30-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, and 14-18 of U.S. Patent No. 10,588,984 B2 (referenced herein as ‘984; commonly owned) in view of Ostrow et al (US 10,076,515 B2, 27 July 2017; published 18 September 2018) and Hecht et al (US 5,578,578 A, 19 April 1995; Published 26 Nov 1996). Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed method in ‘984 necessarily produces (i.e., requires) the instantly claimed composition and would read on the instant claims if it were available as prior art.
Patented claim 1 of ‘984 recites “method of producing tumor-targeting bioconjugates, the method comprising: (a) transfecting cells in vitro with deoxyribonucleic acid (DNA) encoding papilloma virus capsid proteins, wherein expression of the DNA in the cells results in production of the papilloma virus capsid proteins, and the papilloma virus capsid proteins assemble to form proto-capsids; (b) collecting the proto-capsids and subjecting the proto-capsids to a maturation process to form virus-like particles comprising the papilloma virus capsid proteins; and (c) conjugating near infrared phthalocyanine dye molecules to papilloma virus capsid proteins of the virus-like particles, thereby producing the tumor-targeting bioconjugates, each comprising about 50 to about 1000 near infrared phthalocyanine dye molecules, wherein the near infrared phthalocyanine dye molecules become toxic or produce a toxic molecule upon light activation” which reads on “a virus-like particle (VLP) drug conjugates comprising (a)photosensitive molecules and (b) VLPs, wherein the photosensitive molecules are conjugated to capsid proteins of a VLP” as in instant claim 1 in-part, “wherein the photosensitive molecules comprise dye molecules” as in instant claim 25, “wherein the dye molecules comprise phthalocyanine dye molecules” as in instant claim 26, “wherein the VLPs comprise 10-1000 photosensitive molecules” as in instant claim 28, and “wherein the VLP comprises papillomavirus capsid proteins” as in instant claim 30.
Patented claim 3 of ‘984 recites “wherein the papilloma virus capsid proteins are human papilloma virus (HPV) capsid proteins” which reads on “wherein the papillomavirus capsid proteins are human papillomavirus capsid proteins” as in instant claim 31.
Patented claim 4 of ‘984 recites “wherein the HPV capsid proteins comprise HPV L1 capsid proteins or a combination of HPV L1 capsid proteins and HPV L2 capsid proteins” which reads on “wherein the papillomavirus capsid proteins comprise L1 capsid proteins, L2 capsid proteins, or a combination of L1 and L2 capsid proteins” as in instant claim 32.
Patented claim 14 of ‘984 recites “wherein the near infrared phthalocyanine dye molecules comprise IR700 dye molecules” which reads on “which reads on “wherein the phthalocyanine dye molecules comprise the chemical formula C74H96N12Na4O27S6Si3 and dye structure” as in instant claim 27 (i.e., IRDye700DX; see 103 rejection above for chemical formula and structure).
Patented claims 15-18 of ‘984 recites “wherein each of the bioconjugates comprises about 50 to about 500 near infrared phthalocyanine dye molecules”, “wherein each of the bioconjugates comprises about 200 near infrared phthalocyanine dye molecules”, “wherein each of the bioconjugates comprises about 300 near infrared phthalocyanine dye molecules”, and “wherein each of the bioconjugates comprises about 400 near infrared phthalocyanine dye molecules”, respectively, which reads on “wherein the VLPs comprise 10-1000 photosensitive molecules” as in instant claim 28.
‘984 differs from the instant application in that it does not teach that the composition has an isotonicity of 255-345 mOsm/L (related to instant claim 1 in-part).
However, Ostrow teaches that ophthalmic compositions can be formulated to not disrupt the ionic balance of the eye by having an deliverable osmolarity of about 250 to about 350 mOsm/L (see “Osmolarity” para 1 and 3). The reference also teaches that the composition contains organic buffering agents such as 2-(N-morpholino)ethanesulfonic acid (MES) (col 18, lines 21-23) (“2-(N-morpholino)ethanesulfonic acid (MES)” as in instant claim 1 in-part) and tonicity adjusting agents that reduce local irritation by preventing osmotic shock, such as magnesium chloride, sodium chloride in amounts of 0.5% to about 2% (col 18 lines 48-50, 59-61; col 19 line 3).
Finally, Hecht teaches ophthalmic solutions that are physiologically compatible have a pH of 6.8 and an osmolality of between 250 and 350 mOsm/L while containing a low salt concentration (col 4, lines 60-62). The table present in col 5 of the reference teaches that sodium chloride can be present in an amount of 0.01 to 1.0 wt %.
Therefore, it would have been obvious for the tumor-targeting bioconjugates as taught by de los Pinos, to have an isotonicity of 255-345 mOsm/L with a reasonable expectation that the composition would not disrupt the isotonic balance of the eye with a reasonable expectation of success as taught by Ostrow.
It also would have been obvious prior to the effective filing date of the instantly claimed invention to create a composition for treating tumors in the eye containing virus-like particles and photosensitive molecules as taught by de los Pinos, where the composition has a low salt concentration as taught by Hecht, with a reasonable expectation of advantageously having an ophthalmic solution that maintains physiological compatibility, a pH of 6.8, and osmolarity of between 250 and 350 mOsm/L as taught by Hecht.
Rejection 3
Claims 1, 25, and 28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6-8, 18, and 23 of U.S. Patent No. 12,029,794 B2 (referenced herein as ‘794; commonly owned) in view of Ostrow et al (US 10,076,515 B2, 27 July 2017; published 18 September 2018) and Hecht et al (US 5,578,578 A, 19 April 1995; Published 26 Nov 1996). Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed method in ‘794 necessarily requires the instantly claimed composition and would read on the instant claims if it were available as prior art.
Patented claim 1 and 3 recites “a method comprising administering to a subject a virus-like particle (VLP) comprising viral capsid proteins and about 50 to about 1000 photosensitizer molecules” and “wherein the photosensitizer molecules are conjugated to the viral capsid proteins” respectively, which reads on “a virus-like particle (VLP) drug conjugates comprising (a)photosensitive molecules and (b) VLPs, wherein the photosensitive molecules are conjugated to capsid proteins of a VLP” as in instant claim 1 in-part.
Patented claim 2 recites “wherein the photosensitizer molecules comprise dye molecules that are activated by infrared, near-infrared, or ultraviolet light” which reads on “wherein the photosensitive molecules comprise dye molecules” as in instant claim 25.
Patented claims 6-8 recites “wherein the VLP comprises about 100 to about 1000 photosensitizer molecules”, “wherein the VLP comprises about 50 to about 500 photosensitizer molecules”, and “wherein the VLP comprises about 100, about 200, or about 300 photosensitizer molecules” respectively, which reads on “wherein the VLPs comprise 10-1000 photosensitive molecules” as in instant claim 28.
Patented claim 18 recites “a method comprising injecting into a tumor of a subject a virus-like particle (VLP) comprising viral capsid proteins and about 100 to about 500 photosensitizer molecules, wherein the photosensitizer molecules are conjugated to the viral capsid proteins” which reads on “a virus-like particle (VLP) drug conjugates comprising (a)photosensitive molecules and (b) VLPs, wherein the photosensitive molecules are conjugated to capsid proteins of a VLP” as in instant claim 1 in-part and “wherein the VLPs comprise 10-1000 photosensitive molecules” as in instant claim 28.
Patented claim 23 recites “a method comprising administering to a subject a virus-like particle (VLP) comprising viral capsid proteins and about 100 to about 500 photosensitizer molecules, wherein the photosensitizer molecules are conjugated to the viral capsid proteins” which reads on “a virus-like particle (VLP) drug conjugates comprising (a)photosensitive molecules and (b) VLPs, wherein the photosensitive molecules are conjugated to capsid proteins of a VLP” as in instant claim 1 in-part and “wherein the VLPs comprise 10-1000 photosensitive molecules” as in instant claim 28.
‘794 differs from the instant application in that it does not teach that the composition has an isotonicity of 255-345 mOsm/L (related to instant claim 1 in-part).
However, Ostrow teaches that ophthalmic compositions can be formulated to not disrupt the ionic balance of the eye by having an deliverable osmolarity of about 250 to about 350 mOsm/L (see “Osmolarity” para 1 and 3). The reference also teaches that the composition contains organic buffering agents such as 2-(N-morpholino)ethanesulfonic acid (MES) (col 18, lines 21-23) (“2-(N-morpholino)ethanesulfonic acid (MES)” as in instant claim 1 in-part) and tonicity adjusting agents that reduce local irritation by preventing osmotic shock, such as magnesium chloride, sodium chloride in amounts of 0.5% to about 2% (col 18 lines 48-50, 59-61; col 19 line 3).
Finally, Hecht teaches ophthalmic solutions that are physiologically compatible have a pH of 6.8 and an osmolality of between 250 and 350 mOsm/L while containing a low salt concentration (col 4, lines 60-62). The table present in col 5 of the reference teaches that sodium chloride can be present in an amount of 0.01 to 1.0 wt %.
Therefore, it would have been obvious for the virus-like particles conjugated to photosensitive molecules for administration as taught by de los Pinos, to have an isotonicity of 255-345 mOsm/L with a reasonable expectation that the composition would not disrupt the isotonic balance of the eye when administered with a reasonable expectation of success as taught by Ostrow.
It also would have been obvious prior to the effective filing date of the instantly claimed invention to create a composition for treating tumors in the eye containing virus-like particles and photosensitive molecules as taught by de los Pinos, where the composition has a low salt concentration as taught by Hecht, with a reasonable expectation of advantageously having an ophthalmic solution that maintains physiological compatibility, a pH of 6.8, and osmolarity of between 250 and 350 mOsm/L as taught by Hecht.
Response to Arguments
Applicant’s arguments have been fully considered but are not persuasive. Applicant argues the same points as in the above art rejections, namely that Ostrow and Hecht are not analogous art, there is no motivation to select MES and that the claimed MES formulations exhibit unexpected results.
In response, and in order to not be duplicative, the examiner refers Applicant to the above responses to these arguments, which describe why Ostrow and Hecht are analogous art, that the reason Ostrow provides teaching, suggestion, and motivation to select a buffer, including MES, for pH stability, aqueous solution stability, etc., and that MES’ ability to lower protein aggregation was known well before the effective filing date of the instantly claimed invention and was expected. Thus, the arguments are note persuasive and the rejections are maintained.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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/G.R./Examiner, Art Unit 1632
/KARA D JOHNSON/Primary Examiner, Art Unit 1632
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