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 .
Status of Claims
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is in response to the papers filed on December 29, 2025. Claims 1 -4, 7, 14 – 15, 18, 21 – 22, 26, 28 – 33, 35 – 36, and 38 are currently pending. No claims have been amended, canceled, or added in the Applicant’s amendment filed December 29, 2025.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on December 29, 2025 has been considered. An initialed copy of the IDS accompanies this Office Action.
Priority
The present application filed 14 October, 2022, is a 35 U.S.C. 371 national stage filing of International Application No. PCT/ US2021/027727, filed 16 April, 2021, which claims the benefit of Provisional Application 63/010,760, filed 16 April, 2020.
Therefore, the earliest priority date is 16 April, 2020.
Withdrawn Objections/Rejections
Claim Rejection - 35 USC § 112(b)
The rejection of claims 28-33 and 35-36 is withdrawn under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The Applicant has convinced the Examiner that one of ordinary skill in the art would be able to determine what the relative terms “reduces” and “decreases” refer to.
In view of the withdrawn rejection, Applicant’s arguments are moot.
Maintained Objections/Rejections
Claim Rejections - 35 USC § 102
The rejection of claims 1 -4, 7, 14 – 15, 18, 21 – 22, 26, 28 – 31, and 38 is maintained under 35 U.S.C. 102 (a)(1)/(a)(2) as being anticipated by Fillatreau et al. (hereinafter referred to as “Fillatreau”) (WO 2011/147622 A1, published 12 January, 2011), as evidenced by Ingbar et al. (WO 2019/152659 A1, published 08 August, 2019), and Kalil et al. (Kalil AC, Influenza virus-related critical illness: pathophysiology and epidemiology. Crit Care. 2019 Jul 19;23(1):258. doi: 10.1186/s13054-019-2539-x. PMID: 31324202; PMCID: PMC6642581.).
Regarding claim 1, Fillatreau teaches the administration of B cells for any unwanted immune reaction, such as autoimmune disorders (pg. 9, second paragraph). Fillatreau teaches that Acute Respiratory Distress Syndrome (ARDS) is an example of an autoimmune disorder (pg. 13, last paragraph). Fillatreau teaches that these B cells have been isolated from CD19+ cells (pg. 1, second paragraph).
Regarding claim 2, although Fillatreau does not specifically exemplify that ARDS results from hyperoxia, it is well known hyperoxia-induced acute lunge injury is a well-established model of ARDS, as evidenced by Ingbar et al. (pg. 12, lines 18 – 22).
Regarding claim 3, Fillatreau teaches that the autoimmune disorder can be HIV induced (pg. 14, first paragraph).
Regarding claim 4, although Fillatreau dos not specifically exemplify that viral infection is caused by an influenza virus, one of ordinary skill in the art would know that the influenza virus affects the respiratory tract by direct viral infection, as evidenced by Kalil et al. (Abstract).
Regarding claim 7, Fillatreau teaches that the invention uses administration of modified antigen-presenting naive B cells (pg. 4, last paragraph).
Regarding claim 14, Fillatreau teaches engineering resting regulatory B cells (pg. 5, first paragraph).
Regarding claim 15, Fillatreau teaches that the modified B cells secrete IL-10 (pg. 6, second paragraph).
Regarding claim 18, Fillatreau teaches the intravenous administration of these cells (pg. 15, last paragraph).
Regarding claim 21, Fillatreau teaches that the administration can occur once or over multiple days (pg. 16, second paragraph).
Regarding claim 22, Fillatreau teaches that the dose administered may be between about 1,000 to about 1000,000,000 cells per dose (pg. 15, last paragraph).
Regarding claim 26, Fillatreau teaches that the autoimmune disorder can be multiple organ injury syndrome (pg. 13, first paragraph).
Regarding claims 28 – 30, Fillatreau teaches that the instant invention is used for treatment of unwanted immune reactions, such as those involved in autoimmune disorders, immune reactions to therapeutic proteins, and/or allergies (pg. 11, first paragraph) (interpreted as reduces symptoms caused by ARDS, instant claims 28 – 30).
Regarding claim 31, Fillatreau teaches that pharmaceutical composition comprising the B cells further comprises antimicrobials (pg. 16, second paragraph).
Regarding claim 38, Fillatreau teaches that the invention is administered to a human (pg. 11, fourth paragraph).
Fillatreau meets all the limitations of the claims, and therefore, anticipates in the invention.
Note that Fillatreau does not specifically exemplify that the second therapeutic is an anti-inflammatory drug (instant claims 32, 33, 35, and 36).
Response to Arguments as they apply to rejection of claims 1 – 4, 7, 14 – 15, 18, 21 – 22, 26, 28 – 31, and 38 under 35 USC § 102
Applicant’s arguments filed December 29, 2025 have been fully considered but they are not persuasive. Applicant essentially asserts (a) Fillatreau names 230 diseases and disorders, such that a skilled worked would need to make two selections to arrive at the claimed invention (pg. 3, second paragraph); and (b) the Office does not explain why Fillatreau teaches the skilled artisan to select the adult respiratory distress syndrome (pg. 3, third paragraph).
Regarding (a) and (b), Applicant’s arguments are not found persuasive. As an initial matter, the preamble of claim 1 recites “a method of treating ARDS in a subject.”
MPEP 2111.02 teaches
where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation"); Kropa v. Robie.
In the instant case, the claim body teaches the complete invention (administering to the subject a therapeutically effective amount of isolated B cells), and preamble defines the intended use of the invention (treating ARDS). Thus, the preamble is not a claim limitation. The only claim limitation of claim 1 is administering to the subject a therapeutically effective amount of isolated B cells, Fillatreau teaches the administration of B cells for any unwanted immune reaction, such as autoimmune disorders (pg. 9, second paragraph). Fillatreau teaches that these B cells have been isolated from CD19+ cells (pg. 1, second paragraph). Thus, Fillatreau teaches the claim limitations and the 102 rejection of these claims in maintained.
Applicant also notes the issue of “picking and choosing various disclosures,” such that the skilled artisan would have to select the disease from the list of there are 230 diseases and disorders taught by Fillatreau. However, Applicant’s argument is not found convincing. One of ordinary skill in the art would not be “choosing” or “picking” from the list to arrive at the claimed invention, rather, one of ordinary skill in the art would know that isolated B cells can be used to treat autoimmune diseases, and one of ordinary skill in the art would know that ARDS is an autoimmune disease. Thus, Filladreau anticipates the claims.
Claim Rejection - 35 USC § 103
The rejection of claims 32, 33, 35, and 36 is maintained under 35 U.S.C. 103 as being unpatentable over Fillatreau, as applied to the claims 1 , 28 – 31supra, and further in view of Villar et al. (Villar J. et al. dexamethasone in ARDS network. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med. 2020 Mar;8(3):267-276. doi: 10.1016/S2213-2600(19)30417-5. Epub 2020 Feb 7. PMID: 32043986.).
The teachings of Fillatreau in regards to 1 and 28 – 31 is supra.
Fillatreau teaches that pharmaceutical composition comprising the B cells further comprises antimicrobials, but does not specifically exemplify that the second therapeutic is an anti-inflammatory drug (instant claims 32, 33, 35, and 36).
Regarding claims 32, 33, 35, and 36, Villar teaches that early administration of dexamethasone could reduce duration of mechanical ventilation and overall mortality in patients with established moderate to severe ARDS (Abstract). Villar teaches that corticosteroids, such as dexamethasone, attenuate the pulmonary and systemic damage in patients with ARDS because of their potent anti-inflammatory and antifibrotic properties (pg. 3, third paragraph) . Villar teaches that treatment with intravenous dexamethasone attenuates the pulmonary and systemic inflammatory responses (pg. 5, first paragraph).
Therefore, in view of the benefits of administration of dexamethasone to patients with moderate to severe ARDS, including attenuating the pulmonary and systemic inflammatory responses in the patient, as taught by Villar, it would have been prima facia obvious to one of ordinary skill in the art before the effective filing date to substitute the anti-microbials as taught by Fillatreau with the dexamethasone as taught by Villar, with a reasonable expectation of success in reducing the overall mortality of patients with ARDS. It would have been prima facia obvious to combine the cited sources because Fillatreau teaches the administration of B cells with an anti-microbial for the treatment of ARDS, and Villar teaches the effectiveness of using dexamethasone in a clinical trial setting for the treatment of ARDS.
Response to Arguments as they apply to rejection of claims 32, 33, 35, and 36 under 35 USC § 103
Applicant’s arguments filed December 29, 2025 have been fully considered but they are not persuasive. Applicant essentially asserts (a) ARDS is an entirely different disease from EAE and MS, and thus, a skilled artisan would not expect treatment to be effective in treating ARDS and (b) Fillatreau treated EAE with engineered B cells, which is unlike the pending claims (pg. 4, second paragraph); (c) the Applicant teaches unexpected results of successful treatment of ARDS with the B cell administration (pg. 4, fourth paragraph); and (d) Villar does not teach the administration of B cells, and thus does not cure the deficiencies of Fillatreau with respect of claim 1 (pg. 4, last paragraph).
Regarding (a), as noted above, preamble (a method of treating ARDS in a subject) is not a claim limitation. Thus, one of ordinary skill in the art would, as taught by Fillatreau, would know to administer a therapeutically effective amount of isolated B cells.
Regarding (b), Applicant’s argument is not found persuasive. The instantly recited claims do not specify the phenotype of the B cells. Claim 7 teaches various characteristics of B cells, however, these characteristics are listed in the alternative, and thus, it is not a requirement that the cells are naïve.
Furthermore, Applicant notes that a skilled artisan would not expect a method of treating EAE to effectively treat ARDS. However,
MPEP 2143.02 teaches
Conclusive proof of efficacy is not required to show a reasonable expectation of success. OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019) ("To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’"); Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018) ("This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness." (citing to Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007); Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364, 1367–68 (Fed. Cir. 2007) (reasoning that "the expectation of success need only be reasonable, not absolute")).
Thus, based on the teachings of Fillatreau, one of ordinary skill in the art would be able to
determine a course of action for the treatment of ARDS by administering B cells, regardless of the effectiveness of treatment.
Regarding (c), Applicant’s arguments that there are unexpected results are not persuasive.
Moreover, MPEP 716.02(b) states:
the evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992) (Mere conclusions in appellants’ brief that the claimed polymer had an unexpectedly increased impact strength "are not entitled to the weight of conclusions accompanying the evidence, either in the specification or in a declaration."); Ex parte C, 27 USPQ2d 1492 (Bd. Pat. App. & Inter. 1992) (See also; In re Nolan, 553 F.2d 1261, 1267, 193 USPQ 641, 645 (CCPA 1977).
MPEP 716.02(c) indicates that:
unexpected results must be weighed against evidence supporting a prima facie obviousness. In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978); and where the unexpected properties of a claimed invention are not shown to have a significance equal to or greater than the expected properties, the evidence of unexpected properties may not be sufficient to rebut the evidence of obviousness. In re Nolan, 553 F.2d 1261, 1267, 193 USPQ 641, 645 (CCPA 1977). “Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof.” In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967).
Applicant’s assertion that the unexpected results of successful treatment of ARDS with B cells is not found persuasive. As an initial matter, the disclosure does not teach any details about unexpected/surprising results. Further, the pg. 4 of the Remarks refers to the results of Examples 2 – 4, wherein various results are observed 96 hours post treatment with the B cells in the ARDS model in mice. The Applicant concludes that there has been successful treatment after 96 hours. However, it is not conclusive to say that the disease has been treated after 96 hours, when there is no further data provided at other time points (i.e. 96 hours is not enough to declare that a disease has been eradicated). Even if 96 hours provides a treatment, there is no evidence of record that this result is unexpected.
Furthermore, claim 30 of the instant application teaches that the symptoms of ARDS is “selected from the group consisting of a feeling that one cannot get air into the lungs, rapid breathing, low oxygen levels in the blood, and clicking, bubbling or rattling sounds in the lungs when breathing.” In the Remarks, the Applicant references the results of Examples 2 – 4. The results as taught in Example 2 - 4 are not addressing a reduction of the symptoms described in claim 30.
Regarding (d), Applicant notes that Villar does not teach the administration of B cells, and thus does not cure the deficiencies of Fillatreau. Applicant is reminded that none of the references has to teach each and every claim limitation. If they did, this would have been anticipation and not an obviousness-type rejection. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicant’s assertion that Villar does not teach administering B cells is not found persuasive. As an initial matter, Applicant is reminded that the rejection of record is based on the combination of Fillatreau and Villar, wherein Fillatreau clearly teaches administering B cells, and Villar is cited for the administration of dexamethasone. Thus, the rejection of rejection is maintained.
Conclusion
Claims 1 -4, 7, 14 – 15, 18, 21 – 22, 26, 28 – 33 and 38 are rejected.
THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 extension fee 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 VYOMA SHUBHAM TIWARI whose telephone number is (571)272-2954. The examiner can normally be reached M-F 8:30 - 5:30 EST.
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/VYOMA SHUBHAM TIWARI/ Examiner, Art Unit 1634
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638