DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. 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
2. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 July 9, 2026 has been entered.
3. Claims 1, 4, 5, 8, 10 and 20 are pending.
Claims 11-13, 15 and 17-19 have been cancelled.
Claims 1 and 20 have been amended.
Claims 1, 4, 5, 8, 10 and 20 are examined on the merits.
4. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Withdrawn Grounds of Rejection
Claim Rejections - 35 USC § 112
5. The rejection of claims 1, 4, 5, 8, 10 and 20 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in light of the amendment to independent claim 1 and arguments set forth in the Remarks, see Remarks (page 6, 1st complete sentence); and Amendments to the Claims, both submitted July 9, 2026. Claims 11-13, 15 and 17-19 have been cancelled.
6. The rejection of claims 1, 3, 4, 5, 8, 10 and 20 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating or ameliorating luminal B breast cancer with the LAG-3 protein derivative, IMP321 + paclitaxel, does not reasonably provide enablement for treating and ameliorating all cancers with IMP321 + paclitaxel, LAG-3 protein and derivatives thereof is withdrawn in light of the amendment to independent claim 1 and the accompanying arguments set forth in the Remarks, see Remarks (page 8, 4th paragraph); and Amendments to the Claims, both submitted July 9, 2026. Claims 11-13, 15 and 17-19 have been cancelled.
7. The rejection of claims 1, 4, 5, 8, 10 and 20 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 is withdrawn in light of the amendment to independent claim 1, see Amendments to the Claims submitted July 9, 2026. Claims 11-13, 15 and 17-19 have been cancelled.
New and Maintained Objections
Specification
8. The disclosure continues to be objected to because it still contains an embedded hyperlink and/or other form of browser-executable code in the Amendments to Specification submitted July 9, 2026, see lines 3, 5, 6 and 10. These links are not disabled. Applicant is requested to type in a browser the citations as the Examiner has. These citations are still accessible and are clearly browser-executable code.
Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
9. Claim 1 is objected to because of the following informality: the verb, “is” should be cited after the word, “which” on line 3 of the claim.
Correction is required.
Maintained Grounds of Rejection
Claim Rejections - 35 USC § 102
10. 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
11. The rejection of claim(s) 1, 4, 5, 8, 10 and 20 under 35 U.S.C. 102(a)(1) as being anticipated by Brignone et al., (Journal of Translational Medicine 8 (71): 1-11, published 23 July 2010/ IDS reference #4 submitted November 28, 2022) is maintained. Claims 11, 13, 15, 18 and 19 have been cancelled.
Applicant recites their claimed invention and then states the teachings of the prior art, Brignone, see Remarks submitted July 9, 2026, pages 9 and 13-16. Applicant argues “there is no disclosure in Brignone identifying which patients have the characteristics recited in Table 1, so it is not possible to tell from Brignone the characteristics of the responsive patients” and “…no disclosure in Brignone of treatment of the patient subgroups recited in amended claim 1, see Remarks, page 9, last sentence; and page 10, 1st sentence.
Applicant continues arguments pointing out colors within Brignone’s Figure 6A and how it is not possible to determine in Brignone if any of the patients with a low monocyte count were administered 6.25 mg IMP321 and “there is no disclosure in Brignone of treatment of a subject with a low monocyte count with 6.25 mg IMP321 and paclitaxel.”, see page 10; and page 11, sentence in bold format.
Applicant further argues:
- “there is no disclosure in Brignone of treatment of a subject with luminal B breast cancer”;
- “no disclosure in this document of a subject selected exclusively from subjects with an age of less than 65 years”;
-“ there is no disclosure in this document regarding whether any of the patients administered 6.25 mg IMP321 were less than 65 years old and were responsive”; and
-“ there is no disclosure in Brignone identifying which patients have the characteristics recited in Table 1, so it is not possible to tell the characteristics of the responsive patients, including whether or not any patients given 6.25 mg IMP321 were previously treated with taxane chemotherapy and were responsive.”, see pages 11 and 12.
In conclusion, Applicant asserts “Brignone teaches away from selecting patients with a low monocyte count for treatment” and highlights the teachings of their claimed invention, see pages 13-16.
Applicant’s arguments and points of view have been carefully considered but fail to persuade.
Reviewing Brignone there are no apparent colors seen in the reference.
Applicant’s arguments reading on patient response, overall survival and stratification are moot as the claims do not read on such.
While amended, Applicant’s claim 1 cites “wherein the subject is selected from one or more of: [six (6) characteristics]”, see lines 5 and 6. Therefore, from the six (6) requirements only one is required to anticipate the claim.
Brignone discloses the patients had a low monocyte count. Brignone states “…the normal range for monocytes is 0.3 - 0.8 × 109 CD45+CD14+ cells/l whole blood…and therefore many patients and especially the poor responders are monocytopenic at D1”, see page 7, 2nd column (col.), last paragraph (para.). Hence, it is evident the monocyte count is less than about 0.25 x 109 cells/L of blood. Moreover, absent evidence to the contrary, the patients within Brignone that have a low monocyte count would be less than about 0.25 x 109 cells/L of blood prior to treatment. The administration of IMP321 is not solely based upon monocyte count as selection for treatment is dependent upon at least one characteristic.
Some of the patients had no previous taxane chemotherapy, see page 2, Table 1.
The LAG-3 protein, IMP321 is administered with and after paclitaxel at a dosage of 0.25 mg, 1.25 mg and 6.25 mg, see Figure 1 on page 3. The 6.25 mg dosage is within Applicant’s cited range.
Accordingly, the rejection does not fall for the reasons cited herein and of record, wherein the subject has at least four of the characteristics required for selection of treatment.
Brignone discloses treating metastatic breast carcinoma (MBC) with the soluble LAG-3Ig fusion protein or IMP321, which is able to bind MHC class II antigen presenting cells (APCs), see Abstract on page 1; and page 2, 1st column, 1st and 2nd paragraphs. The recipients of the treatment had a low monocyte count, some did not have chemotherapy previous to the instant treatment, 60% were progesterone-receptor positive and 100% were HER2 negative, see Table 1 on page 2; Figure 3 on page 6; and Figure 6A on page 9.
IMP321 was administered during and after chemotherapy, see Study…segment bridging pages 2 and 3; and Figure 1 on page 3. Some patients were excluded if they received prior chemotherapy for MBC, see page 2, Patients, 2nd paragraph.
IMP321 was administered in a dose range from 0.25 mg to 30 mg, see Figure 1 on page 3; Safety segment on page 4; Figure 4 on page 7; and page 10, 1st full paragraph. This range overlaps with the range cited in Applicant’s claims 1 and 20.
11. The rejection of claim(s) 1, 4, 5, 8, 10 and 20 under 35 U.S.C. 102(a)(1) as being anticipated by Dirix et al., (Future Oncology 15/17: 1963-1973, published online, 12 April 2019/ IDS reference #1 submitted December 30, 2025) is maintained. Claims 11, 12 and 17-19 have been cancelled.
Applicant argues the prior art reference, Dirix does not teach “patients that had a low monocyte count (below 0.25 X 109 cells/L of blood at baseline). There is also no disclosure of a subject selected from a subject with Luminal B breast cancer or previously treated with a CDK4/6 inhibitor. There is also no disclosure in Dirix of a subject that has not previously undergone treatment with taxane chemotherapy. Furthermore, the patients described in Dirix are female and at least 18 years of age, so it is also clear that the patients were not selected exclusively from subjects with an age of less than about 65 years, as in the amended claims.”, see Remarks submitted July 9, 2026, paragraph (para.) bridging pages 16 and 17.
Applicant’s arguments and points of view have been carefully considered but fail to persuade.
While amended, Applicant’s claim 1 cites “wherein the subject is selected from one or more of: [six (6) characteristics]”, see lines 5 and 6. Therefore, from the six (6) requirements only one is required to anticipate the claim.
Notwithstanding, Dirix teaches the patients were excluded if they had previous chemotherapy for metastatic breast cancer, see para. bridging pages 1968 and 1969.
The LAG-3, IMP321 dimeric soluble molecule also known as eftilagimod alpha is administered after and during paclitaxel treatment, see page 1969, Dose…segment. As well, as patients were eligible with “…histologically proven, metastatic, ER+ and/or PR+ breast adenocarcinoma…patients with HER-2/neu positive MBC…enrolled if they were ineligible for HER-2/neu targeted therapy)”, see page 1968, last full para.
Administered IMP321 dosages ranged from 6mg up to 30 mg and in combination with paclitaxel, see page 1967, last full para. and para. bridging pages 1967 and 1968; and page 1969, Dose…segment.
“The first-line treatment options for this patient population includes any type of endocrine therapy (preferentially in combination with CDK4/6 inhibitors) is the treatment of choice.”, see page 1963, Epidemiology…segment, 3rd para. And patients that did not have taxane chemotherapy were available for the disclosed method, see para. bridging pages 1968 and 1969.
Hence, the rejection does not fall for the reasons cited herein and of record as one and more characteristics are disclosed by Dirix.
Dirix discloses a study design and rationale, wherein female patients with metastatic estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+) breast adenocarcinoma were administered eftilagimod alpha (IMP321) added to weekly paclitaxel as a first-line chemotherapy versus paclitaxel plus placebo, see page 1967, The AIPAC study; and page 1968, Study design, and Key…segment. Eftilagimod alpha is also known as LAG-3Ig, see title.
These patients were not previously treated with chemotherapy, see sentence bridging pages 1968 and 1969.
In this disclosure, “…this patient population includes any type of endocrine therapy (preferentially in combination with CDK4/6 inhibitors) is the treatment of choice.”, see page 1963, Epidemiology…segment, 3rd paragraph (para.).
IMP321 was administered in a dose range from 6.25 mg to 30 mg, see page 1967, Background…segment, 5th and 6th paragraphs (paras.); para. bridging 1967 and 1968; page 1969, Dose…segment; and Figure 6 on page 1970.
12. The rejection of claim(s) 1, 4, 5, 8, 10 and 20 under 35 U.S.C. 102(a)(2) as being anticipated by Strum et al., WO 2020/037251 A1 (effective filed 16 August 2019). Claims 11-13 and 17-19 have been cancelled.
“Applicant respectfully disagrees and asserts that Strum does not anticipate the invention described by the amended claims. There is no disclosure in Strum describing patients that had a low monocyte count (below 0.25 x 10° cells/L of blood at baseline). There is also no disclosure of a subject selected from a subject with Luminal B breast cancer or previously treated with a CDK4/6 inhibitor. There is also no disclosure in Strum of a subject that has not previously undergone treatment with taxane chemotherapy. Furthermore, Strum does not describe a method treating patients selected exclusively from subjects with an age of less than about 65 years, as in the amended claims.”, see Remarks submitted July 9, 2026, page 17.
While amended, Applicant’s claim 1 cites “wherein the subject is selected from one or more of: [six (6) characteristics]”, see lines 5 and 6. Therefore, from the six (6) requirements only one is required to anticipate the claim.
Contrary to Applicant’s assertions, Strum clearly discloses the treated cancer is a luminal breast cancer, see page 11, lines 20 and 21; and page 72, lines 20 and 21. And the treatment includes IMP321 at a dosages overlapping with Applicant’s in combination with additional therapeutic agents including paclitaxel, wherein the said agents “…are provided in separate dosage forms and are administered approximately simultaneously or at varying times throughout the day, as long as they have a combined effect on the patient, see page 69; page 74, 2nd and 3rd paragraphs (paras.); page 75, line 20; and page 84, line 8. Hence, the rejection does not fall for the reasons cited herein and of record as one and more characteristics are disclosed by Strum.
Strum discloses treating estrogen-related medical disorder including metastatic endocrine therapy resistant breast cancer, hormone receptor positive metastatic breast cancer, estrogen-receptor (ER+) positive breast cancer and ”[i]n one embodiment, the ER+ breast cancer is human epidermal growth factor receptor 2 negative (HER2-)…In one embodiment, the ER+ breast cancer is progesterone receptor-positive (PR+). In one embodiment, the ER+ breast cancer is PR-. In one embodiment, the ER+ breast cancer is PR+ and HER2-…In one embodiment, the ER+ breast cancer is PR- and HER2-.... In one embodiment, the ER+ breast cancer is ER+ late-line metastatic breast cancer…In one embodiment, the ER+ breast cancer is ER+ luminal B breast cancer…” with administration a taxane chemotherapy agent (paclitaxel) and IMP321, see abstract; and page 11; page 15, lines 11-16; page 72, lines 20, 21; page 75, lines 18-21; and page 84, line 8. Absent evidence to the contrary, the patient has not previously undergone treatment with a taxane chemotherapy.
“The therapeutically effective dosage of any active compound described herein will be determined by the health care practitioner depending on the condition, size and age of the patient as well as the route of delivery. In one non-limited embodiment, a dosage from about 0.1 to about 200 mg/kg has therapeutic efficacy, with all weights being calculated based upon the weight of the active compound, including the cases where a salt is employed.
In certain embodiments the pharmaceutical composition is in a dosage form that contains from about 0.1 mg to about 2000 mg, from about 10 mg to about 1000 mg, from about 100 mg to about 800 mg, or from about 200 mg to about 600 mg of the active compound and optionally from about 0.1 mg to about 2000 mg, from about 10 mg to about 1000 mg, from about 100 mg to about 800 mg, or from about 200 mg to about 600 mg of an additional active agent in a unit dosage form. Examples are dosage forms with at least 5, 10, 15, 20, 25, 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 750, 800, 850, 900, 950 or 1000 mg of active compound, calculated alone or in the form of its salt.”, see page 69, lines 15-28.
Double Patenting
13. 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.
14. Claims 1, 4, 5, 8, 10 and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-16 of copending Application No. 18/837,252 (filed August 9, 2024). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims read on treating or ameliorating a metastatic breast cancer that is subtype, luminal B breast cancer which is hormone receptor-positive HER2 negative with a LAG-3 protein or derivative, thereof, wherein the derivative is IMP321. The said therapeutic agents are administered before, with or after administration of paclitaxel. The derivative of LAG-3 comprise domain D1 and the treated population overlap in required characteristics.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
15. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ALANA HARRIS DENT whose telephone number is (571)272-0831. The Examiner works a flexible schedule, however she can generally be reached 8AM-8PM, Monday through Friday.
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, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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ALANA HARRIS DENT
Primary Examiner
Art Unit 1643
15 September 2026
/Alana Harris Dent/Primary Examiner, Art Unit 1643
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