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 .
Continued Examination Under 37 CFR 1.114
1. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on February 28, 2025 has been entered.
2. Claims 1, 5 and 9-15 are pending in the present application. Claims 10-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 20, 2023.
3. Claims 1, 5 and 9 are under examination in the current office action.
Priority
4. 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. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(a)-(d) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, FI20195804, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The foreign priority document does not provide support for the anti-Clever-1 antibody bexmarilimab, or a bexmarilimab biosimilar, as recited by the claims.
Accordingly, for purposes of prior art, the claims have been accorded the effective filing date of September 24, 2020.
Should applicant disagree with the examiner’s factual determination above, applicant should provide evidence that the claim limitation in question is described as required by 35 U.S.C. 112, first paragraph, in the relevant application. This could be accomplished, for example, by pointing out the page and line numbers where the limitations appear.
Withdrawn Claim Rejections
5. The rejection of claims 1, 5 and 9 under 35 U.S.C. 112(a) (enablement) is withdrawn in view of applicant’s persuasive arguments filed 02/28/2025. In particular, provides VL and VH sequence alignments to evidence that the humanized monoclonal antibody disclosed in WO 2017/182705 is the same as the claimed bexmarilimab antibody. Accordingly, there would have been no undue burden to practice the invention as presently claimed.
Maintained and New Claim Rejections
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(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.
6. Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Faron Pharmaceuticals OY (WO 2017/82705 A1; hereinafter “Faron”; listed on 09/24/2020 IDS).
Faron teaches the anti-CLEVER-1 humanized monoclonal antibody VH3/VK5 (see p. 42 lines 1-3; and Table 5 at p. 41) and its use in the treatment of cancer or chronic infections in an individual (p. 6 lines 1-6). As shown in applicant’s response filed 02/28/2025, the VH3 (SEQ ID NO: 18)/VK5 (SEQ ID NO: 30) antibody of Faron is the bexmarilimab antibody as presently claimed.
Faron teaches a method for modulating tumor promoting M2 macrophages into pro-inflammatory M1 macrophages, which increases T-cell activation and leads to the removal of cancer-originated immune suppression (p. 12 lines 16-28)(i.e., improving the antigen presentation capability of Clever-1 positive macrophages), comprising administering to a subject in need thereof an agent capable of binding to specific sequences on the Clever-1 molecule (p. 19 lines 3-8). The agent may be an anti-Clever-1 antibody (p. 4 lines 1-5), such as the FAR02 VH3/VK5 antibody (p. 21 line 19; p. 22 line 2). Faron also teaches that HLA-DR expression on CD14 positive cells (i.e., monocytes) increased with treatment of humanized anti-Clever-1 antibody VH3/VK5 (bexmarilimab) compared to reference human IgGs (p. 42 lines 8-11) (i.e., improving the antigen presentation capability of Clever-1 positive monocytes).
Because Faron discloses the use of the same agent (bexmarilimab) in the same method (administration to a patient) as in the instant invention, Faron’s therapeutic method of administering FAR02 VH3/VK5 (bexmarilimab) would be expected to inherently control lysosomal pH in Clever-1 positive monocytes and/or macrophages as claimed. MPEP § 2112 (I) states “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).
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.
7. Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 7,354,577 (the ‘577 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because in each case the claims encompass the therapeutic administration of the same agent, bexmarilimab or a bexmarilimab biosimilar, to a patient. The ‘577 patent claims recite administration of an agent that inhibits Clever-1 mediated leukocyte binding, wherein the agent is an antagonist monoclonal antibody 3-266 (DSM ACC2519) or 3-372 (DSM ACC2590), which meet the limitation of bexmarilimab or a bexmarilimab biosimilar.
8. Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-5 and 8 of U.S. Patent No. 7,910,097 (the ‘097 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because in each case the claims encompass the therapeutic administration of the same agent, bexmarilimab or a bexmarilimab biosimilar, to a patient. The ‘097 patent claims recite administration of a Clever-1 antagonist antibody, wherein the antibody is monoclonal antibody 3-266 (DSM ACC2510) or 3-372 (DSM ACC2520) or humanized forms thereof, which meet the limitation of bexmarilimab or a bexmarilimab biosimilar.
9. Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 8,722,045 (the ‘045 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because in each case the claims encompass the therapeutic administration of the same agent, bexmarilimab or a bexmarilimab biosimilar, to a patient. The ‘045 patent claim 1 recites administration of an agent that modulates a Clever-1 receptor on macrophages, wherein the agent is an antagonist monoclonal antibody 3-266 (DSM ACC2510) or 3-372 (DSM ACC2520), which meet the limitation of bexmarilimab or a bexmarilimab biosimilar.
10. Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-6 of U.S. Patent No. 10,526,607 (the ‘607 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because in each case the claims encompass the therapeutic administration of the same agent, bexmarilimab or a bexmarilimab biosimilar, to a patient. The ‘607 patent claims recite administration of an anti-Clever-1 antibody capable of counteracting the influence or downregulating the expression of a Clever-1 protein, wherein the antibody is monoclonal antibody 3-266 (DSM ACC2510) or 3-372 (DSM ACC2520) or humanized variants thereof, which meet the limitation of bexmarilimab or a bexmarilimab biosimilar.
11. Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 10,884,000 (the ‘000 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because in each case the claims encompass the therapeutic administration of the same agent, bexmarilimab, to a patient. The ‘000 patent claim 1 recites administration of an agent capable of binding to Clever-1, wherein the agent is the anti-Clever-1 antibody 3-372 (DSM ACC2520) or the antibody VH3/VK5, which meet the limitation of bexmarilimab (VH3/VK5) or a bexmarilimab biosimilar (3-372).
12. Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 10-12 and 16 of U.S. Patent No. 12,371,486 (the ‘486 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because in each case the claims encompass the therapeutic administration of the same agent, bexmarilimab (VH3/VK5), to a patient. The ‘486 patents claims recite administration of an agent capable of binding to Clever-1, wherein the agent is the anti-Clever-1 antibody 3-372 (DSM ACC2520) or the antibody comprising the VH of SEQ ID NO: 18 and the VL of SEQ ID NO: 30 (VH3/VK5), which meet the limitation of bexmarilimab (VH3/VK5) or a bexmarilimab biosimilar (3-372).
13. Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 and 9 of U.S. Patent No. 11,046,761 (the ‘761 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because in each case the claims recite the same agent, bexmarilimab (i.e., the VH3 (SEQ ID NO: 18)/VK5 (SEQ ID NO: 30) antibody). The patented claims also recite that the antibody is capable of modulating M2 macrophages into M1 macrophages, and patented claim 7 recites a pharmaceutical composition comprising the anti-Clever-1 humanized antibody.
The specification of the ‘761 patent indicates that the antibody may be administered to a patient for the treatment of cancer. Therefore, the patented claims render obvious the present invention of claim 1 because it would have been obvious to have administered the antibody of claim 1 to a patient for therapeutic purposes, particularly given that the patented claims also recite a pharmaceutical composition.
The courts have held that a "claim to a method of using a composition is not patentably distinct from an earlier claim to the identical composition in a patent disclosing the identical use," which extend to any and all such uses disclosed in the specification of the earlier patent. Pfizer, Inc. v. Teva Pharmaceuticals USA, Inc., 518 F.3d at 1363 (Fed. Cir. 2008), and Geneva Pharmaceuticals, Inc. v. GlaxoSmithKline PLC, 349 F.3d at 1385-86 (Fed. Cir. 2003). Indeed, as both cases recognized,
[i]t would shock one’s sense of justice if an inventor could receive a patent upon a composition of matter, setting out at length in the specification the useful purposes of such composition, … and then prevent the public from making an beneficial use of such product by securing patents upon each of the uses to which it may be adapted.
Sun Pharmaceuticals Industries, Ltd. v. Eli Lilly and Co., 611 F.3d 1381 (Fed, Cir. 2010), citing Pfizer, 518 F.3d at 1363 n.8 (emphases added); and Geneva, 349 F.3d at 1386 (quoting In re Byck, 48 F.2d 665, 666 (CCPA 1931)).
14. Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of copending Application No. 15/577,132 (reference application). The rejection is maintained for reasons of record and as discussed below.
Although the claims at issue are not identical, they are not patentably distinct from each other because in each case the claims encompass the therapeutic administration of the same agent, bexmarilimab, to a patient. This is a provisional nonstatutory double patenting (NSDP) rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
15. In the response filed 02/28/2025, applicant traverses the rejection and argues that since the present application has an earlier filing date than the co-pending reference application, the provisional double patenting rejection should be withdrawn if it is the only rejection remaining in the application.
16. Applicant’s argument has been considered but is not persuasive. As discussed above, this provisional rejection is not the only remaining rejection in this application, and therefore the provisional NSDP rejection is maintained.
Conclusion
17. Claim 1 is rejected.
Claims 5 and 9 are allowed. The prior art does not teach or reasonably suggest a relationship between Clever-1 inhibition and the lysosomal proton pump vATPase, which controls lysosomal pH within macrophages, or that measuring this lysosomal pH in monocytes can be useful as a means to evaluate the therapeutic efficacy of the anti-Clever-1 antibody bexmarilimab.
18. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. This prior art includes:
Hollmén Maija et al. New tools to prevent cancer growth and spread: a ‘Clever’ approach. British J. Cancer (2020) 123:501-509.
Thomas Lea et al. Selective upregulation of TNFa expression in classically-activated human monocyte-derived macrophages (M1) through pharmacological interference with V-ATPase. Biochemical Pharmacology (2017) 130:71-82.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kimberly A. Ballard whose telephone number is (571)272-2150. The examiner can normally be reached Mon-Fri 8AM - 5PM EST.
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, Jeffrey Stucker can be reached at 571-272-0911. 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.
/KIMBERLY BALLARD/Primary Examiner, Art Unit 1675