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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/4/2025 has been entered.
Status of Claims
Cancelled: 4, 5, 10, 12-22
Examined Herein: 1-3, 6-9, 11, 23-30
Priority
Priority to EP21215193.0 filed on 12/16/2021 and PCT/EP2020/086497 filed on 12/16/2022 is
acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 6/12/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings filed on 6/12/2024 are accepted.
Withdrawn Rejections
The rejection of claims 1, 2, 7-9, 23, 24, and 27-29 under 35 U.S.C. 103 over Omtveit and Nishikawa is hereby withdrawn in view of Applicant’s persuasive arguments that Omtveit does not teach the limitation “wherein the pressure inside the chamber is not more than 0.2 bars higher than the predetermined pressure.” [Remarks 7/6/2026, Page 2, Paragraph 1]
The rejection of claims 1-3, 6-9, 23-29 under 35 U.S.C. 103 over Omtveit, Nishikawa, and Renzi is hereby withdrawn in view of Applicant’s persuasive arguments that Omtveit does not teach the limitation “wherein the pressure inside the chamber is not more than 0.2 bars higher than the predetermined pressure.” [Remarks 7/6/2026, Page 2, Paragraph 1]
The rejection of claims 1, 2, 7-9, 11, 23, 24, and 27-30 under 35 U.S.C. 103 over Omtveit, Nishikawa, and the American Gas Association is hereby withdrawn in view of Applicant’s persuasive arguments that Omtveit does not teach the limitation “wherein the pressure inside the chamber is not more than 0.2 bars higher than the predetermined pressure.” [Remarks 7/6/2026, Page 2, Paragraph 1]
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claims 1-2, 7-9, 23-24, and 27-29 are rejected under 35 U.S.C. 103 as being unpatentable over Omtveit (WO 1999/008716 A2, Published 2/25/1999), in view of Young (US 2005/0089442 A1, Published 4/28/2005) and Nishikawa (US 2003/0076602 A1, Published 4/24/2003).
With respect to claims 1 and 23, Omtveit discloses a method for preparing a freeze-dried composition, lyophilisable precursor material, comprising (i) an amphiphilic material, hydrogenated egg phosphatidylserine, and (ii) a freeze-drying protecting component, propylene glycol and glycerol, comprising: [Page 19, Line 20-24 and Page 28, Line 6-27]
Preparing a liquid mixture comprising said amphiphilic material and said freeze-drying protecting component in a solvent, water, and filling a plurality of vials with the liquid mixture; [Page 19, Line 20-25 and Page 28, Line 6-27]
Introducing said vials into a freeze-drying chamber, said chamber having a respective inner volume; [Page 19, Line 23-26 and Page 28, Line 27-28]
c. Freeze-drying the liquid mixture and obtaining a freeze-dried product. [Page 19, Line 22-24 and Page 28, Line 25-27]
d. Saturating the inner volume of the freeze-drying chamber and the headspace of said vials with a fluorinated gas, perfluoro-n-butane gas, at a predetermined pressure; [Page 19, Line 3-8 & 26-28]
e. Stoppering the vials; [Page 19, Line 3-8 & 26-28, Page 20, Line 12-16]
f. Extracting the gas from the chamber; and [Page 19, Line 15-19, 29-32 and Page 28, Line 27-29]
g. Removing the vials from the chamber; [Page 19, Line 18-19, Page 28, Line 30-32]
wherein said step f. comprises:
insufflating a volume of a second gas, perfluoro-n-butane gas, into said chamber at a pressure higher than the predetermined pressure; [Page 19, Line 29-31, Page 20, Line 12-14, 20-22]
extracting the gas from said chamber; [Page 19, Line 30-33 and Page 28, Line 27-29]
wherein the extraction of the gas is carried out by an extracting system comprising: [Page 20, Line 23-26, 35-37, Page 21, Line 1-3, 14-16]
A vacuum pump (which is a type of gas compressor) for extracting the gas from the chamber; and [Page 21, Line 14-16]
A throttle or first valve. [Page 20, Line 23-26, Page 21, Line 1-3, 14-16] Omtveit discloses the first valve is positioned between the chamber and the vacuum pump/gas compressor, thereby forming an extracting line. [Page 21, Line 14-27] A throttle, by definition, controls the flow of fluids, like gas. Thus, the throttle/first valve controls the flow of gas from the chamber to the vacuum pump/gas compressor.
controlling said extraction of gas from the chamber to the vacuum pump/gas compressor. [Page 21, Line 14-27]
With respect to claim 2 and 24, Omtveit discloses the second gas is perfluoro-n-butane gas. [Page 20, Line 8-10, Page 28, Line 27-29] However, Omtveit further discloses the second gas may be an atmospheric gas such as nitrogen. [Page 20, Line 12-13]
With respect to claims 7, 9, 27, and 29, Omtveit implicitly discloses the control of gas backflow is effected by maintaining the extracting system at a pressure lower than the pressure of the second gas being insufflated inside the chamber and the extracting system is operated to extract the gas from the chamber while maintaining a pressure in the extracting line downstream from said first valve lower than the pressure inside the chamber receiving the second gas. Omtveit discloses overpressure must be maintained in the chamber to assist in flushing residual fluorocarbon gas from the chamber. [Page 20, Line 20-22] Omtveit also discloses gas from the chamber flows into the vacuum pump/gas compressor and condensation vessel of the extracting system, which is downstream from the first valve. [Page 20, Line 25-26 and Page 21, Line 1-3] Overpressure in the chamber indicates that there is higher pressure inside the chamber compared to the pressure outside the chamber, and it is a well-established scientific principle that gas flows from areas of high pressure to low pressure to maintain equilibrium. As a result, a pressure differential between the chamber and the downstream extracting system is created.
Accordingly:
With respect to claims 7 and 27, Omtveit’s disclosure that gas flows from the over-pressurized chamber to the vacuum pump/gas compressor and condensation vessel of the extracting system suggests that the extracting system must be at a lower pressure than the chamber. For this reason, gas backflow is not achievable.
With respect to claims 9 and 29, Omtveit’s disclosure that gas can flow from the over-pressurized chamber to the vacuum pump/gas compressor and condensation vessel of the extracting system via a functional and physical pathway (or “extracting line”), suggests that the pressure in said pathway/extracting line downstream from the first valve must be lower than the pressure inside the vessel receiving the second gas.
Omtveit does not disclose that the pressure inside the chamber is not more than 0.2 bars higher than the predetermined pressure or that the first valve closes if an overpressure of the extracting system is detected with respect to the pressure inside the chamber. (Claim 1 and 23) Omtveit does not disclose that the extracting system further comprises a second valve, positioned on an auxiliary line connected to the extracting line in a location between the first valve and the compressor/vacuum pump, which opens if the pressure of the extracting system exceeds a predetermined value. (Claim 8 and 28)
However, with respect to claims 1 and 23, Young discloses a method of extracting gas from a chamber having a predetermined pressure, 3 to 7 inches of mercury (0.10-0.24 bar) comprising insufflating an inert gas (i.e., nitrogen) into said chamber at a pressure higher than the predetermined pressure, wherein the pressure inside the chamber is raised by 5 to 9 inches or mercury (0.17-0.30 bar). [Young, 0006, 0022]
Moreover, with respect to claims 1 and 23, Nishikawa discloses a system wherein gas in a first sealed chamber is transferred to a second sealed chamber. A check valve is positioned between the first and second chambers. The valve automatically closes when the pressure in the second chamber is detected and exceeds the pressure in the first chamber. [Nishikawa, 0208, 0212, Figure 6]
With respect to claims 8 and 28, Nishikawa discloses the system further comprises a second check valve positioned on an auxiliary line between the first valve and the second chamber. The second check valve opens when the pressure of the second chamber exceeds a predetermined value (the pressure in the first chamber). [Nishikawa, 0209, 0212, Figure 6]
Modifying the method disclosed by Omtveit so that the pressure inside the chamber is 0.17-0.30 bar (including not more than 0.2 bar) higher than the predetermined pressure when the second gas in insufflated into the chamber and by replacing the first valve with a valve that closes if the pressure of the extracting system is higher than the pressure inside the chamber results in the method of claims 1 and 23.
Further modifying the method disclosed by Omtveit by adding a second valve to the extracting system that is positioned between the first valve and the compressor and opens if the pressure of the extracting system exceeds a predetermined value results in the method of claims 8 and 28.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Omtveit so that the pressure inside the chamber is 0.17-0.30 bar (including not more than 0.2 bar) higher than the predetermined pressure when the second gas is insufflated into the chamber and have a reasonable expectation of success. Omtveit discloses a method comprising the step of extracting gas from a lyophilization chamber by insufflating a gas into a chamber having a predetermined pressure at a pressure higher than said predetermined pressure. Similarly, Young discloses a method comprising the step of extracting gas from a chamber comprising insufflating an inert gas into a chamber having a predetermined pressure, 0.10-0.24 bar, at a pressure higher than said predetermined pressure. As a result, the pressure inside the chamber is raised by 0.17-0.30 bar. Thus, an overpressure of 0.17-0.30 bar is applied to the chamber and the claimed range of not more than 0.2 bar overlaps with/lie inside the range disclosed by Young. MPEP 2144.05. Accordingly, Young discloses that extracting gas from a chamber by insufflating an overpressure of gas into a chamber having a predetermined pressure may be carried out by applying an overpressure of 0.17-0.30 bar (including not more than 0.2 bar). Thus, the combined teachings of Omtveit and Young reasonably suggest that the step of extracting gas from the lyophilization chamber disclosed by Omtveit may be carried out by applying an overpressure of 0.17-0.30 bar (including not more than 0.2 bar) to the chamber such that, as a result, the pressure inside the chamber is 0.17-0.30 bars higher than the predetermined pressure. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Omtveit discloses that applying an overpressure of atmospheric gas (i.e., nitrogen) to the chamber may be maintained to assist in flushing residual fluorocarbon gas from the freeze-drying chamber. [Omtveit, Page 20, Line 12-22]. Young discloses that the aforementioned method, wherein the pressure inside the insufflated chamber is 0.17-0.30 bar higher than the predetermined pressure of the chamber, is effective in degassing the chamber. [Young, 0006] Therefore, one would have been motivated by the expectation that an overpressure of 0.17-0.30 bar (including not more than 0.2 bar) would sufficiently flush residual fluorocarbon gas from the freeze-drying chamber disclosed by Omtveit.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Omtveit by replacing the first valve with a valve that closes if the pressure of the extracting system is higher than the pressure inside the chamber and have a reasonable expectation of success. Omtveit discloses a method comprising the step of extracting gas from a freeze-drying chamber via an extracting system. Omtveit discloses that the extracting system comprises a compressor and a first valve, wherein the first valve is positioned on an extracting line between the chamber and the compressor and controls the flow of gas from the chamber to the compressor. Similarly, Nishikawa discloses a system wherein gas is extracted from a first chamber and transferred to a second chamber, wherein a check valve that controls the flow of gas is positioned between the chambers. Nishikawa further discloses that when the pressure in the second chamber is detected and exceeds the pressure in the first chamber, the check valve closes. Accordingly, Nishikawa teaches that a pressure-responsive check valve configured to close when an overpressure in the second confined space is detected and exceeds the pressure in the first confined space can be used to control the flow of gas in a transfer system. Thus, the combined teachings of Omtveit and Nishikawa reasonably suggest that a valve configured to close when an overpressure in the compressor (a second confined space) is detected with respect to the pressure in the chamber (a first defined space), can be used to control the flow of gas in the transfer system in the method disclosed by Omtveit. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Nishikawa discloses that the check valves operate to automatically adjust the internal pressure of the first and second chambers, so that there is almost no pressure difference between the chambers; in this manner, the valves effectively control the gas environment in the chambers. [Nishikawa, 0212] Therefore, one would have been motivated by the expectation that replacing the first valve with a valve that closes if an overpressure inside the compressor is detected would enable the gas environment in the extracting system and the freeze-drying chamber in the method disclosed by Omtveit to be controlled as desired (e.g., so that there is almost no pressure difference between the chambers).
It would be obvious to one of ordinary skill in the art to further modify the method disclosed by Omtveit by adding a second valve to the extracting system that is positioned between the first valve and the compressor and opens if the pressure of the extracting system exceeds a predetermined value and have a reasonable expectation of success. Omtveit discloses a method comprising the step of extracting gas from a freeze-drying chamber via an extracting system. Omtveit discloses that the extracting system comprises a compressor and a first valve, wherein the first valve is positioned on an extracting line between the chamber and the compressor and controls the flow of gas from the chamber to the compressor. Similarly, Nishikawa discloses a system wherein gas is extracted from a first chamber and transferred to a second chamber, wherein a pair of check valves (a first valve and a second valve) that control the flow of gas are positioned between the chambers. More specifically, the first valve is positioned between the first chamber, and the second valve and the second valve is positioned between the first valve and the second chamber. Nishikawa further discloses that when the pressure in the second chamber is detected and exceeds the pressure in the first chamber, the first valve closes and the second valve opens. Accordingly, Nishikawa teaches that a first and second pressure-responsive check valve pair that are configured to close and open, respectively, when an overpressure in the second confined space is detected and exceeds a predetermined value (the pressure in the first confined space), can be used to control the flow of gas in a transfer system. Thus, the combined teachings of Omtveit and Nishikawa reasonably suggest that a first and second pressure-responsive check valve pair that are configured to close and open, respectively, when an overpressure in the compressor (a second confined space) is detected with respect to the pressure in the chamber (a first defined space) can be used to control the flow of gas in the transfer system in the method disclosed by Omtveit. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Nishikawa discloses that the check valve pair operates to automatically adjust the internal pressure of the first and second chambers, so that there is almost no pressure difference between the chambers. In this manner, the valves effectively control the gas environment in the chambers. [Nishikawa, 0212] Therefore, one would have been motivated by the expectation that adding a second valve positioned between the first valve and the compressor that opens if the pressure of the extracting system exceeds a predetermined value (the pressure in the chamber) is detected would enable the gas environment in the extracting system and the freeze-drying chamber in the method disclosed by Omtveit to be controlled as desired (e.g., so that there is almost no pressure difference between the chambers).
Claims 1-2, 3, 6, 7-9, 23-24, 25, 26, and 27-29 are rejected under 35 U.S.C. 103 as being unpatentable over Omtveit, Young, and Nishikawa, as applied to claims 1-2, 7-9, 23-24, and 27-29 above, and further in view of Renzi (US 4,993,171, Patented 2/19/1991).
With respect to claims 1 and 23, Omtveit, Young, and Nishikawa disclose the teachings above.
Omtveit, Young, and Nishikawa do not disclose that the freeze-drying chamber is located in a sterile environment (claim 3 and 25) or that the first valve is located at an edge of a sterile environment (claim 6 and 26).
However, with respect to claims 3 and 25, Renzi discloses a freeze-drying chamber that is located in a sterile environment and isolated from the non-sterile surfaces of external components to prevent contamination. [Renzi, Col. 2, Line 55-58]
However, with respect to claims 6 and 26, Renzi discloses that the freeze-drying chamber is connected to external components including an actuating arm, vacuum source, and valves. [Renzi, Col. 3, 24-53, Figure 4] The freeze-drying chamber is located in a sterile environment and isolated from the non-sterile surfaces of external components (i.e., the actuating arm) to prevent contamination. [Renzi, Col. 2, Line 55-58]
Modifying the method disclosed by Omtveit and Nishikawa by placing the freeze-drying chamber in a sterile environment, results in the method of claims 3 and 25.
Modifying the method disclosed by Omtveit and Nishikawa by placing the freeze-drying chamber in a sterile environment and placing the external components connected to the chamber, including the first valve of the extracting system, outside the sterile environment, including at its edge, results in the method of claims 6 and 26.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Omtveit, Young, and Nishikawa by placing the freeze-drying chamber in a sterile environment and placing the external components connected to the chamber outside the sterile environment and have a reasonable expectation of success. Omtveit, Young, and Nishikawa disclose a method that utilizes a freeze-drying chamber connected to an extracting system comprising a first valve to prepare medical contrast agents. Renzi discloses a freeze-drying chamber connected to external components, wherein the chamber is located in a sterile environment and isolated from the non-sterile surfaces of the external components. Accordingly, Renzi teaches that a freeze-drying chamber can be located in a sterile environment and external components connected to the chamber can be located outside of the sterile environment, including at its edge. Thus, the combined teachings of Omtveit/Young/Nishikawa and Renzi reasonably suggest that the freeze-drying chamber in the method disclosed by Omtveit/Young/Nishikawa can be placed in a sterile environment. Additionally, the external components connected to the chamber, including the first valve of the extracting system, can be located in a non-sterile environment that is on the edge of the sterile environment. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Renzi discloses that the sterility of the freeze-drying chamber is maintained by a variety of well-known methods. However, there is no assurance that the sterility of external components located outside of the freeze-drying chamber (i.e., the hydraulic ram) is maintained. As a result, the non-sterile external components may contaminate the sterile chamber. [Renzi, Col. 1, Line 26-37] Accordingly, Renzi discloses that the freeze-drying chamber should be isolated from non-sterile surfaces to prevent contamination. [Renzi, Col. 2, Line 55-57] Therefore, one would have been motivated by the expectation that placing the freeze-drying chamber in a sterile environment would maintain the sterility of the chamber and placing the external components connected to the chamber outside the sterile environment would prevent contamination of the sterile freeze-drying chamber.
Claims 1-2, 7-9, 11, 23-24, 27-29, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Omtveit, Young, and Nishikawa, as applied to claims 1-2, 7-9, 23-24, and 27-29 above, and further in view of American Gas Association (Purging Principles and Practice, June 2001, Catalog No. XK0101 Third Edition).
With respect to claims 1 and 23, Omtveit, Young, and Nishikawa disclose the teachings above.
Omtveit discloses that the second gas is used to replace the first gas in the chamber. [Omtveit, Page 28, Line 27-29]
Omtveit, Young, and Nishikawa do not disclose that the volume of the second gas insufflated into the chamber is at least three times the inner volume of the freeze-drying chamber.
However, with respect to claims 11 and 30, the American Gas Association (AGA) discloses that the replacement of one gas by another in an enclosed space or chamber may take place by means of dilution or mixing. Accomplishing a satisfactory purge by dilution or mixing requires a volume of inert purge gas that may be four or five times the free space of the chamber being purged. [AGA, Page 4, Col. 1, Paragraph 4-5]
Modifying the method disclosed by Omtveit, Young, and Nishikawa so that the second volume of gas insufflated into the chamber is four or five times the inner volume of the freeze-drying chamber results in the method of claims 11 and 30.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Omtveit, Young, and Nishikawa so that the volume of the second gas insufflated into the chamber is four or five times the inner volume of the freeze-drying chamber and have a reasonable expectation of success. Omtveit, Young, and Nishikawa disclose a method comprising the step of saturating a freeze-drying chamber with a first fluorocarbon gas and replacing the first gas by insufflating a second gas into the chamber, wherein the second gas flushes and/or diffuses residual fluorocarbon gas from the chamber. The AGA discloses that replacing one gas with another in a chamber may take place by means of dilution or mixing and requires a volume of inert purge gas that may be four or five times the free space of the chamber being purged. Accordingly, the AGA teaches that to replace one gas by another in a chamber via dilution or mixing, the volume of an inert purge gas should be four or five times the free space of a chamber that is purged. Thus, the combined teachings of Omtveit/Young/Nishikawa and the AGA reasonably suggest that the volume of the second gas insufflated into the freeze-drying chamber should be four or five times the free space of the freeze-drying chamber to replace the first fluorocarbon gas. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, the AGA discloses that a satisfactory purge by dilution or mixing requires a volume of inert purge gas to be four or five times the free space of the chamber being purged. [AGA, Page 4, Col. 1, Paragraph 4-5] Therefore, one would have been motivated by the expectation that ensuring the volume of the second gas insufflated into the chamber is four or five times the inner volume of the freeze-drying chamber could satisfactorily replace the first gas in the freeze-drying in the method disclosed by Omtveit, Young, and Nishikawa.
Response to Arguments
Applicant’s arguments, filed 7/6/2026, with respect to the rejection of claims 1, 2, 7-9, 23, 24, and 27-29 under 35 U.S.C. 103 have been fully considered and are persuasive. Applicant’s arguments essentially state that Omtveit does not teach the limitation “wherein the pressure inside the chamber is not more than 0.2 bars higher than the predetermined pressure.” [Remarks 7/6/2026, Page 2, Paragraph 1] Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground of rejection is made in view of the references cited above.
Conclusion
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/K.A.C./Examiner, Art Unit 1618
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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