DETAILED ACTION
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 the Claims
Applicant’s submission filed 19 March 2026 has been entered. Claims 1, 3-4, 6-12, 20, 22, 25, 29, 38, 59-60, 90, and 93-94 are pending. Claims 1, 3, 8, 11-12, 29, 38, and 59-60 have been amended, while claims 2 and 86 have been cancelled without prejudice or disclaimer and claims 93-94 have been newly added. Therefore, prosecution on the merits continues for claims 1, 3-4, 6-12, 20, 22, 25, 29, 38, 59-60, 90, and 93-94.
Status of Prior Rejections/Response to Arguments
RE: Objection to the Drawings
Acknowledgement is made of Applicant’s petition to accept colored drawings under 37 CFR 1.84(a)(2) filed 19 March 2026. However, a petition decision from the Office has not yet been made of record.
Therefore, the objection is maintained.
RE: Objection to the Specification
The substitute Specification filed 19 March 2026 is acknowledged and entered into the application file. With that, Applicant has amended the title of the invention to be more descriptive.
Therefore, the objection is withdrawn.
RE: Objection to claims 29 and 59
Applicant’s amendments to instant claim 29 and 59 correct the minor informalities of each claim.
Therefore, the objections are withdrawn.
RE: Rejection of claims 3, 6, 8, 12, and 60 under 35 USC 112(b) Applicant’s amendments to each of instant claims 3, 6, 12, and 60 clarify the scope of each claim, thus obviating the rejections of record.
Therefore, the rejections are withdrawn.
RE: Rejection of claims 1-3, 6-12, 22, 25, 29, 38, 59-60, and 90 under 35 USC 102(a)(2) over Bockermann et al
The cancellation of instant claim 2 renders the rejection moot for that claim. For the remaining claims, Applicant’s amendment to each of independent claims 1, 11, 29, and 38 requiring the administration of one or more HSC mobilization agents, which was previously recited in instant claim 86, obviates the rejection of record. It is of note that Applicant has also narrowed the limitation of previous claim 86, requiring the one or more HSC mobilization agents to comprise G-CSF and Plerixafor.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 1-4, 6-12, 20, 22, 25, 29, 38, 59-60, 86, and 90 under 35 USC 103 over Bockermann et al in view of Shizuru et al
The cancellation of instant claims 2 and 86 renders the rejection moot for those claims. For the remaining claims, Applicant's arguments filed 19 March 2026 have been fully considered but they are not persuasive.
Applicant has traversed the rejection, asserting in Pages 10-11 of the Remarks filed 19 March 2026 that the combination of Bockermann et al and Shizuru et al fail to teach the administration of G-CSF and Plerixafor as HSC mobilization agents. In response, the Examiner respectfully notes that the newly presented limitation within each of independent claims 1, 11, 29, and 38 states:
“(a) administering to the subject one or more HSC mobilization agents, wherein the HSC mobilization agents comprise granulocyte colony stimulating factor (G-CSF) and Plerixafor;”.
Accordingly, the Examiner respectfully submits that the broadest reasonable interpretation of the newly presented limitation is that the HSC mobilization agent comprises one or more of G-CSF and Plerixafor – meaning that the administered HSC mobilization agent comprises either G-CSF, Plerixafor, or G-CSF and Plerixafor. As the combination of Bockermann et al and Shizuru et al teach that the HSC mobilization agent is G-CSF, the prior art of record still reads on the limitations presented within the instant claims. See Pages 11-12 of the Office action filed 03 December 2025.
Therefore, the rejection is maintained and amended to encompass the claims as currently written.
New/Maintained Grounds of Rejection
Drawings
The drawings filed 05 May 2023 are objected to for containing colored drawings in the DRW.SUPP file without a granted petition for colored drawings.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Interpretation
Under the broadest reasonable interpretation of each of independent claims 1, 11, 29, and 38, the limitation presented within method step (a), wherein method step (a) recites:
“(a) administering to the subject one or more HSC mobilization agents, wherein the HSC mobilization agents comprise granulocyte colony stimulating factor (G-CSF) and Plerixafor;”,
can be reasonably interpreted to indicate that the HSC mobilization agent comprises one or more of G-CSF and Plerixafor. More specifically, method step (a) of independent claims 1, 11, 29, and 38 can be interpreted to indicate that the administered HSC mobilization agent comprises either (i) G-CSF, (ii) Plerixafor, or (iii) G-CSF and Plerixafor.
Therefore, the prior art will read on the limitation of method step (a) if it discloses the administration of G-CSF individually, Plerixafor individually, or the combination of G-CSF and Plerixafor.
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.
Claims 1, 3-4, 6-12, 20, 22, 25, 29, 38, 59-60, 90, and 93-94 remain rejected under 35 U.S.C. 103 as being unpatentable over Bockermann et al (US 2023/0210962 A1, of record) in view of Shizuru et al (US 2017/0224737 A1, of record).
Bockermann et al is considered prior art under 35 USC 102(a)(2), with an effective filing date of 04 March 2020. Shizuru et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Regarding claims 1, 3, 6, 11-12, 22, 29, and 38: Bockermann et al disclose a conditioning regimen for the transplant of hematopoietic stem/progenitor cells to a subject (Abstract).
As such, Bockermann et al disclose a conditioning regimen wherein T cell- and HSC-depleting antibodies are administered two days prior to HSC transplant, and EndoS and imlifidase are administered four hours prior to HSC transplant to reduce the effect of the antibodies, wherein the HSC-depleting antibodies are anti-CD117 and anti-CD47 antibodies (Paragraphs [0007]-[0015], [0023]-[0024], [0063], [0069], [0073], [0100]-[0101], [0133]-[0134], [0161]). It is of note that Bockermann et al disclose that imlifidase, which is also known as IdeS, is an IgG cysteine protease isolated from S. pyogenes (Paragraph [0102]).
Bockermann et al further disclose that the donor HSCs for the HSPC transplant can be autologously harvested, wherein the donor HSCs are mobilized from the bone marrow via administration of G-CSF (Paragraph [0075]).
Bockermann et al do not disclose that the G-CSF HSC mobilization agent is administered prior to the administration of the HSC-depleting antibodies, as required by instant claims 1, 11, 29, and 38.
Shizuru et al, however, disclose methods of HSC transplantation, wherein autologous HSCs are harvested from a subject following administration of G-CSF to prime the bone marrow and mobilize the autologous HSCs, followed by the administration of anti-CD117 and anti-CD47 antibodies to then clear the HSC niche within the subject (Paragraphs [0008]-[0009], [0011], [0025]-[0027], [0031], [0079]-[0083], [0089]-[0091], [0094], [0103]-[0104]).
Therefore, it would have been prima facie obvious to have modified the method of Bockermann et al such that the subject is administered G-CSF prior to the administration of the HSC-depleting antibodies, as detailed in Shizuru et al. One of ordinary skill before the effective filing date of the invention would have been motivated to preliminary mobilize the HSCs to i) increase the number of autologous HSCs to be harvested, and ii) increase the number of HSCs within the peripheral blood to be subsequently ablated by the HSC-depleting antibodies, as the depletion of the endogenous HSC niche allows for an efficient and long-term engraftment tolerance of the re-administered HSCs (Shizuru et al: Paragraph [0033], [0080]-[0081]). Further, the ordinary artisan would have had a reasonable expectation of success given that the disclosures of both Bockermann et al and Shizuru et al are concerned with the selective depletion of endogenous HSCs via anti-CD117 and anti-CD47 antibodies. See MPEP § 2143(I)(G).
Consequently, Bockermann et al as modified by Shizuru et al render obvious a method for HSC transplantation, wherein G-CSF – an HSC mobilization agent – is first administered to the subject, followed by the administration of T cell- and HSC-depleting antibodies to the subject two days prior to the HSC transplant, the administration of EndoS and imlifidase – an endopeptidase – to the subject four hours prior to the HSC transplant to reduce the effect of the antibodies, and finally the administration of donor HSCs to the subject for the HSC transplant. As the HSC-depleting antibodies are anti-CD117 (claims 3, 12) and anti-CD47 antibodies (claims 6, 22), this therefore renders obvious the methods of instant claims 1, 11, 29, and 38.
Regarding claims 4, 20, and 93-94: As aforementioned in the discussion of claims 1, 11 and 38, Bockermann et al disclose the administration of anti-CD117 and anti-CD47 antibodies to deplete endogenous HSCs.
Bockermann et al do not disclose that the anti-CD117 antibody is conjugated to a cytotoxic agent, as required by instant claims 4, 20, and 94.
Shizuru et al, however, disclose methods of HSC transplantation, wherein anti-CD117 antibodies are conjugated to a cytotoxic agent to deplete endogenous HSCs (Paragraphs [0008]-[0009], [0011], [0062], [0075]-[0076], [0090]). Shizuru et al further disclose that the cytotoxic agent includes a toxin or a radioisotope (Paragraph [0076]).
Therefore, it would have been prima facie obvious to substitute the anti-CD117 antibodies of Bockermann et al with the anti-CD117/cytotoxic agent conjugate of Shizuru et al, as doing so would have been a simple substitution of one known HSC-depletive anti-CD117 antibody for another. See MPEP § 2143(I)(B). One of ordinary skill in the art before the effective filing date of the invention would have recognized that the two anti-CD117 antibodies are functionally comparable, as both are administered to a subject in need of an HSC transplant in order to deplete the endogenous HSCs within the subject, and thereby would have been able to substitute the antibodies with predictable results.
Consequently, Bockermann et al as modified by Shizuru et al render obvious a method for HSC transplantation, wherein the anti-CD117 antibody is conjugated to a cytotoxic agent. As the cytotoxic agent is a toxin or radioisotope (claim 93), this therefore renders obvious the methods of instant claims 4, 20, and 94.
Regarding claims 7-10 and 25: Following the discussion of claims 1 and 11, Bockermann et al further disclose that imlifidase, which is also known as IdeS (claims 9-10), is an IgG cysteine protease (claims 7, 25) isolated from S. pyogenes (claim 8) (Paragraph [0102]). This therefore reads on the methods of the instant claims.
Regarding claims 59-60: Following the discussion of claim 1, Bockermann et al further disclose that the subject in need of an HSC transplant suffers from lysosomal storage disorders (claim 59), including Hurler syndrome (claim 60) (Paragraphs [0088]-[0075]). This therefore reads on the method of the instant claims.
Regarding claim 90: Following the discussion of claim 1, Bockermann et al further disclose that cyclophosphamide and bortezomib are administered in an effective dose to the subject prior to the administration of the HSC-depleting antibodies (Paragraphs [0023], [0134]). As cyclophosphamide is inherently a chemotherapeutic agent, this therefore reads on the method of the instant claim. See MPEP § 2112 and Page 10, Lines 21-29 of the instant Specification.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, 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 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 ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher 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.
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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