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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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.
Election/Restrictions
Claim 12-14, 16-22 withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Group II, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 12/19/2024.
However, the requirement is still deemed proper and is therefore made FINAL for the reasons provided in the OA of 8/5/2025.
Status of Claims
Cancelled: 4, 5, 10, 12-22
New: 24-30
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Withdrawn Rejections
The objection of claim 1 is hereby withdrawn in view of Applicant’s amendments to claim 1, which now recites “…said chamber having a respective inner volume,” thereby mooting the objection. [Reply 12/4/2025, Page 6]
The rejection of claims 1, 2, 7, 9, and 23 under 35 U.S.C. 103 over Omtveit, in view of Rosenzweig and Krumbholz, is hereby withdrawn in view of Applicant’s amendments to claim 1, which now recites additional limitations. [Reply 12/4/2025, Page 7]
The rejection of claims 1-3, 6-7, and 9 under 35 U.S.C. 103 over Omtveit, Rosenzweig, and Krumbholz, and further in view of Renzi is hereby withdrawn in view of Applicant’s amendments to claim 1, which now recites additional limitations. [Reply 12/4/2025, Page 7]
The rejection of claims 1, 2, 7, 9, and 11 under 35 U.S.C. 103 over Omtveit, Rosenzweig, and Krumbholz, and further in view of Maracchi is hereby withdrawn in view of Applicant’s amendments to claim 1, which now recites additional limitations. [Reply 12/4/2025, Page 7]
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 Nishikawa (US 2003/0076602 A1, Published 4/24/2003).
With respect to claim 1 and 23, Omtveit discloses a method for preparing a fluorocarbon-containing lyophilized contrast agent comprising (i) an amphiphilic material, hydrogenated egg phosphatidylserine, and (ii) a freeze-drying protecting component, propylene glycol and glycerol, which comprises: [Page 19, Line 21-23 and Page 28, Line 6-8]
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 23-25 and Page 28, Line 11-14]
Introducing said vials into a freeze-drying chamber, said chamber having a respective an inner volume; [Page 19, Line 6-8 & 23-26 and Page 28, Line 25-28]
c. Freeze-drying the liquid mixture and obtaining a lyophilized product. [Page 19, Line 23 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 3-7 & 26-27]
e. Stoppering the vials; [Page 19, Line 8-9 & 27-28]
f. Extracting the gas from the chamber; and [Page 19, Line 15-18, 30-33 and Page 28, Line 28-30]
g. Removing the vials from the chamber; [Page 19, Line 18-19]
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, wherein the pressure inside the chamber is not more than 0.2 bars (120 mm Hg = 0.16 bar) higher than the predetermined pressure; [Page 19, Line 29-31, Page 23, Line 20-23, Page 38, Line 6-14, and Figure 6]
extracting the gas from said chamber into a condensation vessel connected to 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 20-22]
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 21, Line 14-16] Omtveit discloses the first valve is positioned on the vacuum pump/gas compressor which connects the chamber to the external condenser (container), thereby forming an extracting line. [Page 21, Line 14-27] A throttle controls the flow of fluids, like gas. Thus, the first valve (throttle) controls the flow of gas from the chamber into the condensation vessel.
controlling said extraction of gas. [Page 21, Line 14-27]
With respect to claim 2 and 24, Omtveit discloses the second gas is perfluoro-n-butane gas. [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 claim 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 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 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 claim 7 and 27, Omtveit’s disclosure that gas flows from the over-pressurized chamber to the condensation vessel 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 claim 9 and 29, Omtveit’s disclosure that gas is able to flow from the over-pressurized chamber to the condensation vessel 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 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 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 claim 1 and 23, Nishikawa discloses a system wherein gas in a first chamber is transferred to a second chamber through a check valve. When a pressure in the second chamber is detected and exceeds the pressure in the first chamber, the check valve automatically closes. [Nishikawa, 0208 and Figure 6]
With respect to claim 8 and 28, Nishikawa discloses the system comprises a first and second check valve. The second valve is positioned on an auxiliary line in a location between the first valve and the second chamber and opens if the pressure of the second chamber exceeds a predetermined value (the pressure in the first chamber). [Nishikawa, 0209 and Figure 6]
Modifying the method disclosed by Omtveit by replacing first valve (throttle) with a pressure-responsive check valve that closes if an overpressure of the extracting system is detected with respect to the pressure inside the chamber, results in the method of claim 1 and 23.
Further modifying the method disclosed by Omtveit by adding a second pressure-responsive check valve to the extracting system that is positioned on a location between the first valve and the vacuum and opens if the pressure of the extracting system exceeds a predetermined value, results in the method of claim 8 and 28.
It would be obvious to one of ordinary skill in the art to modify the method by Omtveit by replacing the first valve (throttle) with a pressure-responsive check valve that closes if an overpressure of the extracting system is detected with respect to the pressure inside the chamber and have a reasonable expectation of success. Omtveit discloses a method comprising transferring gas from a freeze-drying chamber through an extracting line to an external condenser, wherein a first valve is positioned on the extracting line and controls the flow of gas from the chamber to the condenser. Similarly, Nishikawa discloses a system wherein gas in a first chamber is transferred to a second chamber through a check valve, wherein the check valve controls the flow of gas from the first chamber to the second chamber. Nishikawa further discloses when a pressure in the second chamber is detected and exceeds the pressure in the first chamber, the check valve automatically closes. Nishikawa establishes that a pressure-responsive check valve that is configured to close when an overpressure in a second confined space is detected and exceeds the pressure in a first confined space can be used to control the flow in a gas transfer system. Thus, the combined teachings of Omtveit and Nishikawa suggest that a pressure-responsive check valve can be implemented in the method disclosed by Omtveit to control the gas transfer from the freeze-drying chamber to the condenser. Therefore, it is reasonable to expect the method disclosed by Omtveit may be modified by replacing the first valve (throttle) with a pressure-responsive check valve that closes if an overpressure of the extracting system is detected with respect to the pressure inside the chamber. 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. In the instant case, Nishikawa discloses the valve serves as a control system for controlling the gas environment in the sealed chambers. [Nishikawa, 0212] Therefore, one would have been motivated by the expectation that the aforementioned modification would enable the gas environment in the extracting system and the freeze-drying chamber to be controlled as desired in the method disclosed by Omtveit.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Omtveit and Nishikawa by adding a second pressure-responsive check valve to the extracting system that is positioned on a location between the first valve and the vacuum and opens if the pressure of the extracting system exceeds a predetermined value and have a reasonable expectation of success. Omtveit and Nishikawa disclose a method comprising transferring gas from a freeze-drying chamber through an extracting line to an external condenser, wherein a first valve is positioned on the extracting line and controls the flow of gas from the chamber to the condenser. Omtveit and Nishikawa disclose the first valve is a pressure-responsive check valve that closes if an overpressure of the extracting system is detected with respect to the pressure inside the chamber. Nishikawa discloses a system wherein gas in a first chamber is transferred to a second chamber through a first and second check valve. The second valve is positioned on an auxiliary line in a location between the first valve and the second chamber. When a pressure in the second chamber is detected and exceeds the pressure in the first chamber, the first check valve automatically closes and the second check valve automatically opens. Nishikawa establishes that a second pressure-responsive check valve configured to open when an overpressure in a second confined space is detected and exceeds the pressure in a first confined space, can be used in conjunction with a first pressure-responsive valve to control the flow of gas in a transfer system. Thus, the combined teachings of Omtveit and Nishikawa further suggest that a second pressure-responsive check valve can be implemented in the method to control the gas transfer from the freeze-drying chamber to the condenser. Therefore, it is reasonable to expect the method disclosed by Omtveit and Nishikawa may be modified by adding a second pressure-responsive check valve to the extracting system that is positioned on a location between the first valve and the vacuum and opens if the pressure of the extracting system exceeds a predetermined value. 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. In the instant case, Nishikawa discloses the valves serve as a control system for controlling the gas environment in the sealed chambers. [Nishikawa, 0212] Therefore, one would have been motivated by the expectation that the aforementioned modification would enable the gas environment in the extracting system and the freeze-drying chamber to be controlled as desired in the method disclosed by Omtveit and Nishikawa.
Claims 1-3, 6-9, 23-29 are rejected under 35 U.S.C. 103 as being unpatentable over Omtveit and Nishikawa, as applied to claim 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 claim 1, Omtveit and Nishikawa disclose the teachings above.
Omtveit and Nishikawa do not disclose the freeze-drying chamber is located in a sterile environment (claim 3 and 25) or the first valve is located at an edge of a sterile environment (claim 6 and 26).
However, with respect to claim 3, 6, 25, and 26, Renzi discloses a freeze-drying chamber connected to an extracting system comprising a vacuum source and valves. Renzi discloses the chamber is located in a sterile environment to isolate said chamber from non-sterile surfaces to prevent contamination, while the extracting system is isolated from the sterile environment but located on the edge of the environment. [Renzi, Col. 2, Line 55-57 and Figure 4]
Modifying the method disclosed by Omtveit and Nishikawa by placing the freeze-drying chamber in a sterile environment, results in the method of claim 3 and 25.
Modifying the method disclosed by Omtveit and Nishikawa by placing the first valve at an edge of a sterile environment, results in the method of claim 6 and 26.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Omtveit and Nishikawa by placing the freeze-drying chamber in a sterile environment and the first valve at the edge of a sterile environment and have a reasonable expectation of success. Omtveit and Nishikawa disclose a method that utilizes a freeze-drying chamber connected to an extracting system comprising a first valve. Renzi discloses a freeze-drying chamber connected to an extracting system, wherein the chamber is located in a sterile environment to isolate said chamber from non-sterile surfaces to prevent contamination, while the extracting system is isolated from the sterile environment and is located on the edge of said sterile environment. Renzi establishes that a freeze-drying chamber can be located in a sterile environment and an extracting system connected to the chamber can be located in a non-sterile environment that is on the edge of said sterile environment. Thus, the combined teachings of Omtveit/Nishikawa and Renzi suggest the freeze-drying chamber in the method disclosed by Omtveit/Nishikawa can be located in a sterile environment and the extracting system connected to the chamber can be located in a non-sterile environment that is on the edge of said sterile environment.
Therefore, it is reasonable to expect the method disclosed by Omtveit and Nishikawa may be modified by placing the freeze-drying chamber in a sterile environment and the first valve at an edge of said sterile environment. One would have been motivated to do so 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. In the instant case, Renzi discloses 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 the aforementioned modification could prevent contamination in the freeze-drying chamber in the method disclosed by Omtveit and Nishikawa.
Claims 1, 2, 7-9, 11, 23, 24, and 27-30 are rejected under 35 U.S.C. 103 as being unpatentable over Omtveit and Nishikawa, as applied to claim 1, 2, 7-9, 23, 24, 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 claim 1, Omtveit and Nikishawa discloses the teachings above.
Omtveit discloses the second gas is used to replace the first gas in the chamber. [Page 28, Line 27-29]
Omtveit and Nishikawa do not disclose 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 claim 11 and 30, American Gas Association (AGA) discloses the replacement of one gas by another in an enclosed space or chamber takes place by means of dilution or mixing. To accomplish 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 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 results in the method of claim 11 and 30.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Omtveit 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 and Nishikawa disclose a method comprising the step of saturating a freeze-drying chamber with a first gas and replacing the gas by insufflating a second gas into the chamber. The AGA discloses the replacement of one gas by another in a chamber takes 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. The AGA establishes that 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/Nishikawa and the AGA 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 in order to replace the first gas. Therefore, it is reasonable to expect the method disclosed by Omtveit and Nishikawa may be modified 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. 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. In the instant case, the AGA discloses 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] Therefore, one would have been motivated by the expectation that the aforementioned modification could satisfactorily replace the first gas in the freeze-drying in the method disclosed by Omtveit and Nishikawa.
Response to Arguments
Applicant’s arguments, filed 12/4/2025, with respect to the rejection of the pending claims over Omtveit, Rosenzweig, Krumbholz, Renzi, and Maracchi have been fully considered and are persuasive. Applicant’s arguments essentially state that the cited art does not teach the instant claims as amended. Therefore, the rejection has been withdrawn. [Reply 12/4/2025, Page 7] However, upon further consideration, a new ground of rejection is made in view of the references cited above. The new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAILA A CRAIG whose telephone number is (703)756-4540. The examiner can normally be reached Monday-Friday 0800-1600.
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/K.A.C./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618