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 .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/01/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 1 is objected to because of the following informalities: “A method at treating….” the word “at” should be amended to “for” or “of”.
Appropriate correction is required.
Claim 2 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 1. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, and 8-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Leuzzi et al (Neurol Neuroimmunol Neuroinflamm. 2015 Apr 9; hereinafter "Leuzzi;" See IDS 05/01/2025).
Regarding claims 1-3, and 8-11: Leuzzi explored the effects of a protracted treatment on neurologic outcome, in “a single-arm, open-label, 6-month extended phase 2 trial in which the enrolled patients received a monthly treatment of 50 mL of autologous erythrocytes loaded with 2 vials of 250 mg of dexamethasone phosphate (DSP) by EryDex (EryDel, Urbino, Italy) procedure.” Leuzzi disclosed that “[o]bservational studies have suggested that betamethasone may be effective in improving neurologic functions in patients with AT oral betamethasone (0.1 mg/kg),5 but corticosteroid side effects were quickly observed. To overcome these side effects and explore the effects of a more protracted treatment on neurologic outcome, we recently performed a single-arm, open-label, 6-month extended phase 2 trial in which the enrolled patients received a monthly treatment of 50 mL of autologous erythrocytes loaded with 2 vials of 250 mg of dexamethasone phosphate (DSP) by EryDex (EryDel, Urbino, Italy) procedure.” (See Leuzzi p. 1-2 2nd col.). Further Leuzzi taught that “[a]fter 6 infusions, patients experienced a clinical improvement of about 5 points on the International Cooperative Ataxia Rating Scale (ICARS)8 and a significant improvement in adaptive behavior, assessed by Vineland Adaptive Behavior Scales (VABS)” (See Leuzzi p.2, col. 2, 2nd para). Leuzzi tested EryDex in patients with mean age of 10.6 years (See Abstract), which falls within the claimed age range for claim 1. It is also noted that two tested patients were 8 years old, which falls within the claimed age range for claims 1 and 2. Table 1 noted ICARS change was -4 from baseline for one of the patients, -5 from base line in ICARS 7-30. Because reduction in ICARS represents improvement, the data demonstrates neurological improvement following EryDex treatment in patients who were 8 years old. As such, Leuzzi expressly taught treating AT patients within the claimed age ranges.
Leuzzi taught 250 mg DSP in 50 ml autologous erythrocytes and 9.4±0.8 mg/bg od DSP for 24 months. (See Abstract and p. 2, col.2 last para). As such Leuzzi taught administration of at least 5mg DSP.
As such every element of the claims is anticipated by Leuzzi.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 4-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Leuzzi et al (Neurol Neuroimmunol Neuroinflamm. 2015 Apr 9; hereinafter "Leuzzi;" See IDS 05/01/2025).
Regarding claims 4-7: The teachings of Leuzzi are set forth above. It is noted that Leuzzi did not teach the exact claimed doses of DSP loaded into erythrocytes. It is however, noted that Leuzzi taught that amount of DSP incorporated into erythrocytes is a parameter that can be optimized. In particular, Leuzzi taught that they optimized a DSP dose which was previously 6.7±6.9 to 9.4±0.8 mg/bag. A person of ordinary skill in the art following these teachings would have been motivated to select an appropriate dosing of DSP encapsulated within erythrocytes for administration including within the recited ranges in claims 4-7. The optimization is considered routine adjustment of a known loading parameter to obtain desired amount of DSP incorporated into erythrocyte preparation.
Claims 12-17 and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Leuzzi et al (Neurol Neuroimmunol Neuroinflamm. 2015 Apr 9; hereinafter "Leuzzi;" See IDS 05/01/2025) in view of Mambrini et al (WO2014181309A1; Published Nov 14, 2014; hereinafter “Mambrini;” See IDS 05/01/2025).
Regarding claims 12, 16: The teachings of Leuzzi are set forth above. It is noted that Leuzzi did not teach a method of making erythrocytes loaded with DSP as required by the claim. (See Mambrini claim 9). However, Mambrini taught a process of making Dexamethosone loaded erythrocytes using the claimed method. It would have been obvious for a person of ordinary skill in the art to arrive at the claimed method using the erythrocyte loading method of Mambrini. Both references are directed to the same EryDex technology and the same therapeutic agent, DSP. Applying a known loading procedure to the DSP loaded erythrocytes of Leuzzi would have been the predictable use of a known technique to prepare the same type of therapeutic product. It is also noted that claim 3 of Mambrini taught that the second hypotonic solution brings the erythrocytes to an osmolality between 200 and 170 mOsm/Kg as required by claim 16.
Regarding claim 13-15, and 17-19: Example 1 of Mambrini taught that “The erythrocytes, separated from 50 mL of whole blood [as required by claims 18-19] by means of a centrifugal system of the "Latham Bowl" type spinning at 5600 rpm, are washed with 750 mL of saline solution at a washing speed of 225 mL/min and transferred into the transfer bag. [This reads on step (a) and (b)(i) of claim 13, step (a) of claim 14, step (a)-(b) of 15].
A quantity of 300 mL of a first hypotonic solution having an osmolality of 200 mOsm/kg is added to the transfer bag, which is then incubated on a stir plate at room temperature for 5 minutes. [This reads on step (b)(ii) of claim 13, step (b) of claim 14, step (c) of claim 15]. The first hypotonic solution is then removed by centrifugation (Bowl) until a volume of about 80 mL is reached.
The erythrocytes thus concentrated are transferred back into the transfer bag to which 64 mL of a second hypotonic solution with an osmolality of 180 mOsm/kg are then added. The bag is then incubated at room temperature on a plate under stirring for 5 minutes. [This reads on step (b)(iii) of claim 13, step (c) of claim 14, step (d) of claim 15 and claim 17].
After incubation, the erythrocytes are concentrated using a hemoconcentration filter and about 80 mL of ultrafiltrate is collected in the reservoir to which a slight negative pressure is applied by means of a vacuum pump. [This reads on step (b)(iv) of claim 13].
The erythrocytes thus concentrated are then retrieved and transferred to a transfer bag. The drug of interest, in this example dexamethasone sodium phosphate (25 mg/mL), was pre-mixed with approximately 1 1 mL of water for injectable solutions (the preparation has an osmolality of about 20 mOsm/kg) and added to the concentrated erythrocytes by injection in the transfer bag. [This reads on step (b)(v) of claim 13, step (d) of claim 14 and step (e) of claim 15].
The content of the transfer bag is then incubated at room temperature on a plate under stirring for 10 minutes. A quantity of 3 mL of a sealing solution (with an osmolality of 3800 mOsm/kg) is then added.” [This reads on step (b)(vi) of claim 13, step (e) of claim 14].
A skilled artisan would have had a reason to employ the particular Mambrini process because Mambrini expressly taught that the process was developed to improve the efficiency of erythrocyte loading and reported substantially improved encapsulation efficiency, while using substantially reduced amount of DSP solution. (See Mambrini p. 4, lines 10-15). The claimed process therefore represents the application of Mambrini’s disclosed erythrocyte loading technique to its expressly contemplated DSP-AT treatment rather than a patentably distinct process.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Leuzzi et al (Neurol Neuroimmunol Neuroinflamm. 2015 Apr 9; hereinafter "Leuzzi;" See IDS 05/01/2025) in view of ATTeST-IEDAT-02-2015 Study (First posted June 20, 2018 ; hereinafter “ATTeST;” See PTO-892).
Regarding claim 20: The teachings of Leuzzi are set forth above. Leuzzi did not teach subjects having weight between 9-15kg as required by the claim. It is however, noted that ATTeST indicated that the subjects must have a body weight less than 15 kg. (See ATTeST, p. 11). As such it would have been obvious for a person of ordinary skill in the art to adapt the EryDex treatment taught by Leuzzi for lower weight pediatric patients with AT, particularly in view of teachings of ATTeST. Selecting an appropriate weight would have constituted a routine clinical adaptation of the known EryDex treatment rather than a change in the therapeutic mechanism or active agent. The claimed subject matter therefore represents a patient selection limitation that would have been obvious to one of ordinary skill in the art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-12 and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 10849858 in view of Leuzzi et al (Neurol Neuroimmunol Neuroinflamm. 2015 Apr 9; hereinafter "Leuzzi;" See IDS 05/01/2025).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the reasons indicated below.
Regarding claims 1-3, and 8-11: Claim 4 of the reference application taught a method of loading erythrocytes using dexamethasone sodium phosphate for the treatment of ataxia telangiectasia. While the reference application did not teach or suggest a subject less than about 10 years of age, comprising administering to the subject at least 5 mg of dexamethasone sodium phosphate (DSP), as indicated above, this would have been obvious in view of teachings of Leuzzi as indicated above.
Regarding claims 4-7: As indicated above it is noted that Leuzzi did not teach the exact claimed doses of DSP loaded into erythrocytes. It is however, noted that Leuzzi taught that amount of DSP incorporated into erythrocytes is a parameter that can be optimized. For the reasons indicated above, a person of ordinary skill in the art following this teachings would have been motivated to select an appropriate dosing of DSP encapsulated within erythrocytes for administration including within the recited ranges in claims 4-7.
Regarding claim 12 and 16: Claim 4 of the reference application taught a method of loading erythrocytes using dexamethasone sodium phosphate, for the treatment of ataxia telangiectasia. While the reference application did not teach or suggest a subject less than about 10 years of age, comprising administering to the subject at least 5 mg of dexamethasone sodium phosphate (DSP), as indicated above, this would have been obvious in view of teachings of Leuzzi as indicated above.
Claims 13-15 and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 10849858 in view of Leuzzi et al (Neurol Neuroimmunol Neuroinflamm. 2015 Apr 9; hereinafter "Leuzzi;" See IDS 05/01/2025) and further in view of Mambrini et al (WO2014181309A1; Published Nov 14, 2014; hereinafter “Mambrini;” See IDS 05/01/2025).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the reasons indicated below.
Regarding claims 13-15 and 17: The teachings of the reference application, Leuzzi and Mambrini are set forth above. A skilled artisan would have had a reason to employ the particular Mambrini process in view of Leuzzi and the reference application because Mambrini and the reference application expressly taught that the process was developed to improve the efficiency of erythrocyte loading and reported substantially improved encapsulation efficiency, while using substantially reduced amount of DSP solution. (See Mambrini p. 4, lines 10-15). The claimed process therefore represents the application of Mambrini’s disclosed erythrocyte loading technique to its expressly contemplated DSP-AT treatment rather than a patentably distinct process.
Claim 20 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 10849858 in view of Leuzzi et al (Neurol Neuroimmunol Neuroinflamm. 2015 Apr 9; hereinafter "Leuzzi;" See IDS 05/01/2025) in view of ATTeST-IEDAT-02-2015 Study (First posted June 20, 2018 ; hereinafter “ATTeST;” See PTO-892).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the reasons indicated below.
The teachings of the reference application, Leuzzi and Mambrini are set forth above. The reference application taught a method to treat AT using erythrocyte loaded DSP. As such it would have been obvious for a person of ordinary skill in the art to adapt the EryDex treatment taught by Leuzzi in view of the reference application for lower weight pediatric patients with AT, particularly in view of teachings of ATTeST. Selecting an appropriate weight would have constituted a routine clinical adaptation of the known EryDex treatment rather than a change in the therapeutic mechanism or active agent. The claimed subject matter therefore represents a patient selection limitation that would have been obvious to one of ordinary skill in the art.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12311059 in view of Leuzzi et al (Neurol Neuroimmunol Neuroinflamm. 2015 Apr 9; hereinafter "Leuzzi;" See IDS 05/01/2025), Mambrini et al (WO2014181309A1; Published Nov 14, 2014; hereinafter “Mambrini;” See IDS 05/01/2025) and ATTeST-IEDAT-02-2015 Study (First posted June 20, 2018 ; hereinafter “ATTeST;” See PTO-892).
The same reasoning as indicated above, apply.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAGAMYA VIJAYARAGHAVAN whose telephone number is (703)756-5934. The examiner can normally be reached 9:00a-5:00p.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher M. Babic can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JAGAMYA NMN VIJAYARAGHAVAN/ Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633
Prosecution Insights