DETAILED OFFICIAL 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 .
Examiner Note
It is noted that all references hereinafter to Applicant’s specification (“spec”) are to the published application US 2024/0075211, unless stated otherwise. Further, any italicized text utilized hereinafter is to be interpreted as emphasis placed thereupon.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 29-36 are rejected under 35 U.S.C. 103 as being unpatentable over Weikart et al. (US 2015/0290080; “Weikart”), in view of Reinhard et al. (US 6,331,174; “Reinhard”) and Felts et al. (US 2013/0041241; “Felts”).
Regarding claim 29, Weikart discloses vessels, such as vials and syringes/syringe barrels, which: (i) are formed from thermoplastic and define a wall and interior lumen [Abstract; Figs. 3-4; 0003-0004, 0006, 0009-0011, 0014-0015, 0034-0035, 0042]; (ii) include a coating set on the interior wall surface (that which faces the lumen where a pharmaceutical composition is contained) [0043, 0053-0055, 0065, 0072]; (iii) include an ophthalmic drug (liquid) suitable for intravitreal injection in the lumen, thereby defining a “pre-filled pharmaceutical package”, said ophthalmic drug being a VEGF inhibitor, i.e. anti-VEGF such as Ranibizumab (Lucentis®) or Avastin (Bevacizumab) [0117, 0119, 0121] (see MPEP 2131.02(II)); and (iv) a closure such as stopper or plunger which closes the lumen and exhibits a surface (“front face”) facing the liquid ophthalmic drug formulation [Figs. 3-4; 0014-0015, 0026; claim 1].
The (ii) coating set on the interior wall surface may include (1) a tie layer of SiOxCyHz, where x is from 0.5 to 2.4, y is from 0.6 to 3, and z is from 2 to 9 (each range being an approximation based on the use of “about” preceding each value) [0055, 0057, 0063, 0073]; (2) a barrier layer of SiOx, where x is from (about) 1.5 to 2.9 [0053-0054, 0065-0067]; and (3) a pH protective layer of SiOxCyHz, where x is from 0.5 to 2.4, y is from 0.6 to 3, and z is from 2 to 9 (same as tie coating/layer) [0072-0073]; wherein x and y atomic ratios are measured by XPS, and z atomic ratio is measured by Rutherford backscattering or forward scattering [0039]. The positioning of the layers/coatings relative to the wall and lumen is: wall/tie/barrier/pH protective/lumen, of which reads on the claimed position of the corresponding tie, barrier, and optional pH protective coatings/layers as defined by the “facing” surface claim language.
The coatings/layers are formed via deposition (PECVD) from the vapor phase, from organosilicon (organosiloxane) precursors such as octamethylcyclotetrasiloxane (OMCTS) (e.g. for the pH protective layer) [0008, 0031-0033, 0038, 0065-0066, 0089, 0102].
The thermoplastic wall of the vessel may be any of, inter alia a cyclic olefin (co)polymer (COP, COC), a polyester (such as PET, PEN), polypropylene, or polycarbonate, with cyclic olefins being preferred [0046-0047, 0052, 0132, 0136; claim 3].
The aforecited (2) barrier layer prevents oxygen, carbon dioxide, and other gases from entering the vessel – see also [0133].
Weikart is silent regarding the pre-filled vessels, i.e. pre-filled pharmaceutical packages having been subject to sterilization with gases, wherein subsequent thereto, the gas residuals are lower than required by ISO 10993-7.
Reinhard teaches that the addition of ceramic material layers based on SiOxCy (via deposition processes such as PECVD) to the inner surface(s) of pharmaceutical vessels formed from cyclin olefin thermoplastics provides enhanced barrier properties with respect to gases in order to counteract the permeability of the thermoplastic thereto (whereas the cyclic olefin thermoplastic provides a barrier to water vapor). Reinhard also teaches that the aforesaid are to be highly resistant to sterilization mediums/processes including gamma radiation, ethylene oxide (EO), and/or autoclaving for greater than 20 min at 121°C, as the pharmaceutical vessels, in pre-filled form are sterilized (e.g. with EO) and required to exhibit low impurities/precipitates thereafter [Abstract; col. 2 ln. 35-67; col. 3 ln. 7-21; col. 4 ln. 1-28; col. 6 ln. 23-65; col. 7 ln. 1-27].
Felts is directed to substantially identical pre-filled pharmaceutical packages relative to those of Weikart, in particular thermoplastic syringes/vials which include the interior lumen being coated with barrier/pH-protective layers via PECVD (of substantially similar or identical empirical formulas), formed from siloxane precursors such as OMCTS, and having an anti-VEGF liquid drug formulation such as Avastin or Lucentis® contained/sealed in the lumen [Abstract; 0018-0020, 0023-0026, 0028, 0037, 0042, 0050-0051, 0058, 0064, 0105-0106, 0109-0110, 0116, 0118, 0124, 0179, 0310; claim 64]. Felts teaches that the pre-filled pharmaceutical package (after it has been filled) may be subject to a sterilization process such as exposure to EO gas [0074-0075, 0310], of which is commonly recognized in the art as a suitable sterilization process.
The foregoing prior art are directed to pre-filled pharmaceutical vessels inclusive of ceramic barrier layers intended to prevent transmission of (sterilant or other) gases through the vessel wall and contacting the pharmaceutical formulation contained in the lumen of the vessel – the aforecited prior art are directly analogous to the claimed invention(s).
In view of the combined teachings of the foregoing, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to have modified the pre-filled pharmaceutical package of Weikart by subjecting it to sterilization via exposure to EO gas in order to sterilize the package (eliminate microbial/bacterial contamination) and thus render it suitable for safe delivery of the pharmaceutical formulation (an anti-VEGF) contained therein. Based on the combined teachings of Reinhard and Felts, the use of EO as sterilant would have been well-recognized in the art as suitable for the intended use, and in particular for thermoplastic cyclic olefin vessels including ceramic-based barrier layers, which contain anti-VEGF drugs; where the barrier layer disclosed by Weikart (based on the aforecited disclosure thereof, and the teachings of Reinhard) would have been recognized as being resistant to, and/or capable of preventing ingress of, the EO gas during sterilization to prevent the formation of impurities/precipitates in the package thereafter.
In accordance with the aforesaid modifications, the pre-filled vessel of Weikart set forth above would have been subject to sterilization via exposure to EO gas.
With respect to the foregoing modification, given that claim 29 does not require the pre-filled pharmaceutical package to be subject to sterilization with a particular gas, e.g. does not require sterilization with EO, the scope of the claim is such that the sterilization gas may be any gas, where sterilization may be conducted under any concentration, temperature, pressure, and humidity, and for any duration. As such, the pre-filled vessel of modified Weikart, having been subject to sterilization via exposure to EO gas, would have been identical or substantially identical to the claimed invention in terms of layers and materials, in terms of the drug contained therein, and in terms of the sterilization parameters, and therefore would have necessarily exhibited gas residual levels present after sterilization which would have been lower than required by ISO 10993-7, absent a showing of factually supported objective evidence to the contrary. See MPEP 2112(V); MPEP 2112.01(I) and (II); MPEP 2113(I) and (II); MPEP 2111.01(II); and MPEP 2145 and 2145(I).
The pre-filled vessel of Weikart, in accordance with the modification above (hereinafter “modified Weikart”), reads on the ophthalmic drug in a pre-filled pharmaceutical package defined by claim 29.
Regarding claim 30, the rejection of claim 29 above reads on the package defined by claim 30. That is, in the absence of factually supported objective evidence to the contrary, there is a reasonable expectation that the pre-filled vessel of modified Weikart would have necessarily exhibited the claimed stability of less than 2% for the duration of at least six months at a temperature of 2-8° C following the sterilization. See MPEP 2112(V); MPEP 2112.01(I) and (II); MPEP 2113(I) and (II); MPEP 2111.01(II); and MPEP 2145 and 2145(I).
Regarding claim 31, the rejection of claim 29 above is incorporated herein by reference (not repeated) and reads on the package defined by each and every limitation of claim 31.
Regarding claim 32, the rejection of claim 30 above reads on the package defined by claim 32. That is, there is a reasonable expectation that the pre-filled vessel of modified Weikart would have necessarily exhibited the claimed stability of less than 2% for the duration of at least one year at a temperature of 2-8° C following the sterilization, absent a showing of factually supported objective evidence to the contrary. See MPEP sections cited above.
Regarding claims 33-34, in view of the rejection of claim 29 above, Weikart is silent regarding the pre-filled pharmaceutical package/vessel being contained in a sealed outer package which is permeable to EO, in which the pre-filled pharmaceutical package/vessel is sterile and essentially free of EO.
Felts teaches that commonly, the pre-filled and sterilized vessels are wrapped in a sterile (outer) package before use; and also teaches that the pre-filled vessels (with the ophthalmic drug filled therein) may be subject to sterilization as an alternative to the vessels being sterilized prior to filling [0021, 0022, 0074, 0075]. Reinhard teaches that the outer package is permeable to EO, whilst being impermeable to particles and bacteria, such that the outer package and the (pre-filled) vessel may sterilized together outside of the clean room environment [col. 3].
In view of the combined teachings of the aforecited prior art, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to have modified the pre-filled pharmaceutical package/vessel of modified Weikart by having placed it in an EO gas-permeable, particulate/bacteria impermeable outer packaging, prior to or after sterilization (e.g., with EO gas), in order to prevent contamination of the pre-filled package/vessel with particulate matter and/or bacteria, and/or in order to also sterilize the interior environment of the outer packaging in which the pre-filled vessel remains until use.
As such, the pre-filled pharmaceutical package of Weikart, as modified, would have included all of the features set forth above in the ejection of claim 29 (essentially free of, or free of EO in the lumen), and would have been contained in an EO gas-permeable outer packaging, thereby reading on the package defined by each of claims 33-34.
Regarding claim 35, in view of the rejection of claim 31 above, the rejection of claim 30 above is incorporated herein by reference and reads on the package defined by claim 35.
Regarding claim 36, in view of the rejections of claim 31 and claim 35 above, the rejection of claim 32 above is incorporated herein by reference and reads on the package defined by claim 36.
Response to Arguments
Applicant’s arguments presented on p. 5 of the Remarks filed 01 April 2026 (hereinafter “Remarks”), directed to the rejection of claims 30, 32, and 35-36 under 35 U.S.C. 112(b) previously set forth in the Non-Final Rejection dated 01 October 2025 (hereinafter “NFOA”) [id., ¶5-13], have been fully considered and found persuasive. As such, the 112(b) rejection has been withdrawn, and the Examiner thanks Applicant for clarification of the issues.
Applicant’s arguments presented on p. 8–p. 9 of the Remarks regarding US 2019/0000919 to Brockmeyer et al. (“Brockmeyer”) not constituting prior art due to its effective filing date, 18 November 2015, being the same effective filing date of the instant application by way of US Provisional Application 62/257,208, have been found persuasive. As such, the grounds of rejection under 35 U.S.C. 103 previously set forth in the NFOA which relied upon Brockmeyer have been withdrawn.
However, as previously stated [NFOA, ¶17], Brockmeyer was relied upon in an optional manner, and the grounds of rejection based thereupon (i.e., modifications (B) and (C) [NFOA, ¶29-33]) were presented in the alternative to those based upon Weikart taken in view of the combined teachings of only Reinhard and Felts (i.e., modification (A)).
Applicant’s arguments presented on pp. 5-8 of the Remarks regarding the rejection under 35 U.S.C. 103 over Weikart in view of Reinhard and Felts have been fully considered but not found persuasive, and the corresponding grounds of rejection previously set forth in the NFOA are maintained hereinabove.
Applicant asserts that nothing in the combination of Weikart and Felts would have taught or suggested a person having ordinary skill in the art to expect that the gas residuals present after sterilization would have been lower than required by ISO 10993-7, as claimed, and that the gas residuals level after sterilization constitutes an unexpected result [Remarks, p. 6]. Thereafter, Applicant asserts that the grounds of rejection appear to rely upon Reinhard for the concept that a person of ordinary skill would have expected the low level of gas residuals after sterilization, and that the grounds of rejection combine unrelated teachings of Reinhard to conclude that the barrier layer of SiOxCy serves as a barrier against EO gas.
However, the grounds of rejection do not rely upon Reinhard for a teaching or suggestion that one of ordinary skill in the art would have expected a low level of gas residuals after sterilization, and do not state or purport that Reinhard teaches that the ceramic material is a barrier to EO gas, as asserted. Rather, Reinhard is relied upon specifically for the teaching(s) that the plastic pharmaceutical vessel, having the inner surface thereof coated with the SiOxCy ceramic material, are highly resistant to EO sterilization processes [Reinhard, Abstract; col. 2 ln. 35-60; col. 5 ln. 34-38; col. 7 ln. 1-11]. When taken in combination with the teachings of Felts – that it was known/recognized to sterilize prefilled pharmaceutical packages having the aforesaid ceramic material coating on the inner surface with EO gas – the grounds of rejection establish that it would have been prima facie obvious to sterilize the prefilled pharmaceutical package of Weikart via EO gas sterilization.
Resultant from the prima facie obvious modification to the package of Weikart based upon the foregoing combined teachings of Reinhard and Felts, the grounds of rejection then establish that the package of Weikart would have necessarily exhibited gas residuals subsequent EO sterilization within the levels required by the ISO 10993-7 standard, absent objective evidence to the contrary.
In view of the foregoing, Applicant has not provided the necessary objective evidence and technical reasoning demonstrating that the prefilled pharmaceutical package of Weikart, after having been subject to EO gas sterilization, would not necessarily exhibit the claimed level of gas residuals in accordance with ISO 10993-7, as is required to sufficient rebut the established prima facie case of obviousness. See MPEP 2112(V), MPEP 2112.01(I), MPEP 2145, and MPEP 2145(I).
For at least these reasons above, Applicant’s arguments have not been found persuasive.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Michael C. Romanowski whose telephone number is (571)270-1387. The Examiner can normally be reached M-F, 09:30-17:30.
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/MICHAEL C. ROMANOWSKI/Primary Examiner, Art Unit 1782
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