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 .
Applicant's reply to the previous Office action, dated August 28, 2025, has been received. No claim amendments were submitted with this reply.
Claims 1-8, 10-13, 15-16, and 18-24 are currently pending in the application. Claims 7, 12, 19-22 and 24 remain withdrawn from consideration pursuant to the restriction requirement dated April 15, 2022.
Claims 1-6, 8, 10-11, 13, 15-16, 18 and 23 are therefore under examination before the Office.
The rejections of record can be found in the previous Office action, dated February 28, 2025.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-6, 8, 10-11, 13, 15-16, 18 and 23 are rejected 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.
Applicant argues that the specification provides clear, quantitative guidance for this term, stating that an effective amount of radiolabeled anti-CD45 antibody depletes lymphocytes without depletion of neutrophils, or with less than 10% or 20% reduction in neutrophils, and such relative terms are permitted where the specification supplies an appropriate standard for measurement.
Applicant's arguments have been considered fully but are not found to be persuasive.
The claims do not recite a specific percentage of depletion of neutrophils. The exact word is "substantially". The term "substantially" is not defined or recited anywhere in the specification. There is nothing to tie the term "substantially" to any specific percentage of depletion of neutrophils.
The standard for the use of the term "substantially" is whether or not one of ordinary skill in the art would know what was meant by "substantially" in view of the general guidelines contained in the specification. MPEP 2173.05(b)(III)(D).
The closest guidance presented in the specification is found at Example 3 and Figure 2, which describes a median change in absolute neutrophil count by -0.03, or a reduction of 3%. This is contrasted with the much broader scope recited at page 8, which permits less than 10% or 20% reduction in the subject's neutrophils.
Since the specification does not give a clear indication of what the term "substantially is meant to encompass, and the only working example is broadly different than the textual guidance of the specification, the ordinary practitioner would not be adequately appraised of the metes and bounds of such a limitation.
This rejection is therefore maintained.
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.
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.
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.
Claims 1-6, 8, 10-11, 13, 15-16, 18 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Matthews (Blood. 1999 Jan 15;93(2):737-45, cited in IDS) in view of Louis (Blood. 2009 Mar 12;113(11):2442-50, cited in IDS), Qasim (Sci Transl Med. 2017 Jan 25;9(374), U.S. patent 5,273,738 (cited in IDS, hereafter referred to as "the '738 patent"), and Beatty (U.S. patent 4,921,690).
Applicant argues that Beatty does not teach the use of unlabeled anti-CD45 antibodies, and the teachings of Beatty are limited to only the T84.66 antibody, and for this reason, the teachings of Beatty cannot be extrapolated to apply to anti-CD45 antibodies. Applicant further argues that Beatty teaches away from the simultaneous administration of radiolabeled and unlabeled antibodies, as Beatty teaches that sequential administration of unlabeled and then radiolabeled antibodies is preferred. Applicant further argues that the claimed methods solve a long-felt, unmet need in the field of CAR-T cell therapy conditioning with an unexpected improvement in safety.
Applicant's arguments have been considered fully but are not found to be persuasive.
Beatty is explicit in teaching that it is "possible to increase biodistribution by combining the pretreatment and treatment steps so as to administer unlabeled and labeled antibody simultaneously" (col. 3, line 67 through col. 4, line 2). Beatty also teaches that "[t]hough the examples illustrate the enhanced biodistribution of particular antibodies to a particular marker substance or antigen (CEA), the instant invention is not to be construed to be limited to the exemplified antibody-antigen pairs" (col. 13, lines 61-63). This is a clear suggestion that the methods of Beatty are applicable to other antibodies. The teachings of Beatty, when applied to the method of Matthews, would be reasonably expected to perform in a similar way. Applicant has not presented evidence that this is not the case.
As stated previously, disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). "A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994). "The prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
"The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). MPEP 2123.
The teachings of Beatty are explicit in disclosing simultaneous administration of radiolabeled and unlabeled antibody, and that this principle is applicable to other antibody-antigen combinations beyond those that are explicitly disclosed. Simultaneous administration of radiolabeled and unlabeled antibody is also claimed by Beatty in claim 6.
With regards to Applicant's assertion of unexpected results and long-felt, unmet need to a known problem in the art, Applicant has not established a connection between the claimed properties and the asserted features. There is nothing in Applicant's specification that demonstrates that a combination of radiolabeled and unlabeled antibodies gives the claimed function of not depleting neutrophils. Applicant is invited to present evidence that the claimed combination of radiolabeled and unlabeled antibodies grants properties that would not have been expected in view of the prior art in order to address this issue. Attorney arguments cannot take the place of evidence in the record. MPEP 2145(I).
Furthermore, it was also known in the art by Matthews that treatment with low doses of an 131I-labeled anti-CD45 antibody is not myeloablative and does not result in fatal nonhematopoietic toxicity (page 743, left column, second paragraph). Additionally, Louis further teaches that lymphodepleting antibodies such as anti-CD45 are an attractive, less toxic option for lymphodepletion as opposed to chemotherapy or radiation because they are highly cell-specific and cause little bystander cell damage (page 2448, left column, second paragraph).
Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). The fact that Applicant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious, MPEP 2145(II).
In the absence of evidence to the contrary, there is nothing to suggest that the elements of the claimed combination are performing anything other than their expected, usual functions to affect a predictable result.
This rejection is therefore maintained.
Conclusion
No claim is allowed.
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 PETER JOHANSEN whose telephone number is (571)272-0280. The examiner can normally be reached Monday-Friday, 8:00 to 4:00.
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/PETER JOHANSEN/Examiner, Art Unit 1644
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1645