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 .
Application Status
Claims 1 and 48-56 are pending and examined on the merits herein.
Grounds of Rejection Withdrawn
All previous rejections and objections of claims 2, 4, 8-9, 12-17, 19, 23-24, 27-30, and 46-47 are rendered moot by claim cancellation.
Previous objection to the specification regarding the trademark for Alexa fluor™ is withdrawn in view of specification amendment.
Previous objection to claim 1 is withdrawn in view of claim amendment.
Previous rejection of claim 1 under U.S.C. 102 is withdrawn in view of claim amendment.
The non-statutory double patenting rejections of claim 1 regarding patent US 9,453,836, US 11,633,397 and copending application 16/985,924 are withdrawn in view of claim amendment.
Specification
Objection maintained
The use of the term nanobody (page 10), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Response to Arguments
Applicant's arguments filed October 7, 2025 have been fully considered but they are not persuasive.
Applicant submits: Regarding "nanobodies," Applicant does not use this word in the present application in a manner limited to any trademark. Rather, Applicant uses the term "nanobody" as a generic term to indicate a type of antibody-like protein. Any trademark rights notwithstanding, such use of the term nanobody is common in scientific publications, as evidenced for example, by the issuance of many hundreds of US patents including the term "nanobody" as a general descriptor of a type of antibody-like proteins, with no indication of trademark status. Recent examples of such patents include: US 12,370,264; US 12,399,180; US 12,410,216; and US 12,378,306.
In response: The examiner cannot subjectively determine when a trademark should or should be employed in regard to a term that has a registered trademark. In regards to other patents that contain the term “nanobody” without a trademark, the examiner Is not responsible for the actions of other examiners and human error is always possible.
Claim Objections
New Objection Necessitated by Amendment
Claim 52 objected to because of the following informalities: “SUFFICIENT” in line 2 is written in all capitals, please correct to “sufficient”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
New Objection Necessitated by Amendment
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claim 48 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
In the amendment filed October 7, 2025, claim 48 was added to recite “wherein the amount of leronlimab or a CCR5-binding fragment thereof is further sufficient to bind between 85-98% of TNBC cells expressing CCR5 in the subject.” This is not supported by the instant disclosure. The instant specification has support for an in vitro binding efficiency of up to 98% with cell lines transfected to express CCR5. There is no support or quantification of the binding efficiency of leronlimab done in a subject. Even though MDA-MB-231 is an established triple negative breast cancer (TNBC) cell line, the addition of exogenous CCR5 expression does not demonstrate leronlimab would bind to any TNBC cells with the same efficiency in vitro or in a subject after administration.
Given the apparent difference in the breadth of the claims, and the pertinent disclosures, it is submitted that this clearly illustrates that such amendments have in fact introduced new concepts, thereby violating the written description requirement as set forth under 35 U.S.C. §112, first paragraph. For these reasons, it is not apparent that Applicant had originally contemplated the subject matter encompassed by the claims at the time the application was filed.
Otherwise this issue might be resolved if Applicant were to point to other disclosures in the specification, including the claims, as originally filed, which are believed to provide the necessary written support for the language of the instant claims.
Claim Rejections - 35 USC § 103
New Objection Necessitated by Amendment
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 and 49-56 are rejected under 35 U.S.C. 103 as being unpatentable over Velasco-Velázquez (Cancer research 72.15 (2012): 3839-3850; PTO-892) as evidenced by ECACC (catalogue no. 92020424; no date available, downloaded November 2025; PTO-892); Dhody (HIV Clin Trials. 2018 Jun;19(3):85-93; PTO-892) and Jacobson (Antimicrob Agents Chemother. 2010 Oct;54(10):4137-42; PTO-892) as evidenced by Kaplon (mAbs, 11(2), 219–238; PTO-892).
Regarding claims 1 and 55-56, Velasco-Velázquez teaches that cancer metastasis is regulated by chemokines in the microenvironment and that CCL5 facilitates breast cancer disease progression by recruiting and modulating the activity of inflammatory cells which subsequently remodel the tumor microenvironment (page 3839, col 2, para 2). Velasco-Velázquez further teaches that CCL5/CCR5 signaling is preferentially active in the basal and HER-2 subtypes and that CCR5+ cells displayed increased invasiveness, indicating that CCR5 contributes to the metastatic phenotype of basal breast cancer cells (page 3840, col 1, para 2; Figures 1 C and D). Velasco-Velázquez further demonstrated increased metastasis in MDA-MB-231 cells (Fig 2). As evidenced by ECACC, cell line MDA-MB-231 is a highly aggressive, invasive and poorly differentiated triple-negative breast cancer (TNBC) cell line (key characteristics). Velasco-Velázquez teaches that using drugs originally developed to prevent the interaction of CCR5 with the gp120 from HIV-1, maraviroc (a CCR5 antagonist with full FDA approval for HIV treatment) and vicriviroc (another CCR5 antagonist), they demonstrate that CCR5 inhibition blocked breast cancer cell, including MDA-MB-231, invasiveness in vitro and efficiently reduced metastatic colonization in vivo (page 3840, col 1, para 2; Fig 3). Thus, the method of Velasco-Velazquez teaches treating TNBC comprised of a CCR5 inhibitor.
Regarding claims 49-50, Velasco-Velázquez teaches that CCR5 antagonists block breast cancer calcium signaling by 65 or 90% which is mediated by CCL5 binding (Page 3844, col 2, para 1; Figure 3).
Regarding claims 51-54 Velasco-Velázquez teaches that in a 3D invasion assay CCR5 antagonists inhibited breast cancer cell (MDA-MB-231) invasion (figures 4A-D). Velasco-Velázquez further teaches that in a mouse model of lung metastasis treatment with the CCR5 inhibitor maraviroc showed significant reduction in both the number and size of pulmonary metastases (figures 5A and B).
Velasco-Velázquez does not teach that the CCR5 inhibitor is leronlimab.
Regarding claims 1 and 55-56, Dhody teaches that PRO 140 is a humanized IgG4, κ monoclonal antibody that binds to the C–C chemokine receptor type 5 (CCR5) with high affinity (introduction). Dhody further teaches that PRO140 is a long acting single agent maintenance regimen for HIV (abstract conclusions) and that it offers several potential advantages over existing therapies in terms of infrequent weekly dosing, favorable tolerability, and limited drug–drug or –food interactions (discussion para 1).
As evidenced by Kaplon, leronlimab is another name for PRO140.
Regarding claim 48, Jacobson teaches that receptor occupancy was accessed for fluorescently labeled PRO 140 on lymphocytes at >85% on patients in both dose groups assessed, 5 and 10 mg/kg (figure 3; page 4140, col 2, para 5).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to substitute the CCR5 antibody leronlimab as taught by Dhody in the method of treating metastases with a CCR5 antagonist as taught by Velasco-Velázquez. The ordinary artisan would have been motivated to do so because Velasco-Velázquez teaches that CCL5/CCR5 signaling is preferentially active in the basal and HER-2 subtypes and that CCR5+ cells displayed increased invasiveness and demonstrated that small molecule inhibitors that blocked CCR5 blocked breast cancer cell invasiveness in vitro and efficiently reduced metastatic colonization in vivo. Dhody teaches that PRO140 (leronlimab) is a humanized IgG4 mAb that blocks CCR5 that is a long acting single agent maintenance regimen for HIV and that it offers several potential advantages over small molecule therapies in terms of infrequent weekly dosing, favorable tolerability, and limited drug–drug or –food interactions. Jacobson teaches that receptor occupancy was accessed for fluorescently labeled PRO 140 on lymphocytes at >85% on patients in both dose groups assessed, 5 and 10 mg/kg, demonstrating that leronlimab has high in vivo binding efficiency and that an effective dose could be determined that would results in 85-98% of TNBC with CCR5 expression bound. The ordinary artisan has a reasonable expectation of success in utilizing the CCR5 inhibitor leronlimab with to decrease or block metastasis of triple negative breast cancer with benefit to the patients of more convenient dosing, good tolerance and limited interactions.
Conclusion
No claims allowed.
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 AMBER K FAUST whose telephone number is (703)756-1661. The examiner can normally be reached Monday - Thursday 9:00am-6:00pm EST.
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/AMBER K FAUST/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643