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 .
Response to Amendment and Arguments
2. Claims 1, 4, 5, 8, 10-13, 15 and 17-20 are pending.
Claims 3, 6, 7, 9, 14 and 16 have been cancelled.
Claims 1, 10-13, 17 and 20 have been amended.
Claims 1, 4, 5, 8, 10-13, 15 and 17-20 are examined on the merits.
Information Disclosure Statement
3. The information disclosure statement (IDS) filed November 28, 2022 failed to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because references #2 and #3 on sheet 2 are not legible. In response, Applicant submitted another IDS with the legible two references on December 30, 2025. They have been read, reviewed, nor considered.
However, Applicant’s IDS filed March 5, 2026 while considered, the Examiner notes reference #1 on sheet 2 had incorrect spelling/ initials for the author. Applicant is requested for future submissions all information therein is reviewed and correct.
Withdrawn Objection
Specification
4. The title of the invention is now descriptive, see Amendments to the Specification submitted December 30, 2025.
Withdrawn Rejections
Claim Rejections - 35 USC § 103
5. The rejection of claim(s) 1, 4, 5, 8, 10-13, 15 and 17-20 under 35 U.S.C. 103 as being unpatentable over Brignone et al., Journal of Translational Medicine 8 (71): 1-11, published 23 July 2010 (IDS reference #4 submitted November 28, 2022), and further in view of Immuntep AIPAC Phase IIb Clinical Results & Update Global Webcast Slides (20 pages, March 25, 2020 (IDS reference #14 submitted January 23, 2025) and Triebel et al., WO 2016/110593 A1 (published 14 July 2016) EP 2 044 949 A1 (11 pages, published April 8, 2009) is withdrawn in light of Applicant informing the Office
the Webcast Slides (20 pages, March 25, 2019) were submitted January 23, 2025 and not in 2019 as previously cited in the first action on the merits (FAOM) mailed August 11, 2025 on page 19, segment 13, see Remarks submitted December 30, 2025, paragraph (para.) bridging pages 16 and 17. Applicant follows this information noting the 2019 publication date is incorrect and is actually March 25, 2020 and therefore “the Webcast slides is not prior art to the instant application through the exception provided in 35 U.S.C. §102(b)(1).” with proof in a press release released March 25, 2020, see page 17 of the Remarks, 2nd para. and Miscellaneous Incoming Letter submitted December 30, 2025. Claims 3, 6, 7, 9, 14 and 16 have been cancelled.
6. The rejection of claim(s) 1, 4, 5, 8, 10-13, 15 and 17-20 under 35 U.S.C. 103 as being unpatentable over Drix et al., (Future Oncology 15/17: 1963-1973, published online, 12 April 2019), and further in view of Immuntep AIPAC Phase IIb Clinical Results & Update Global Webcast Slides (20 pages, March 25, 2019 (IDS reference #14 submitted January 23, 2019) and Triebel et al., WO 2016/110593 A1 (published 14 July 2016) is withdrawn in light of Applicant informing the Office
the Webcast Slides (20 pages, March 25, 2019) were submitted January 23, 2025 and not in 2019 as previously cited in the first action on the merits (FAOM) mailed August 11, 2025 on page 19, segment 13, see Remarks submitted December 30, 2025, paragraph (para.) bridging pages 16 and 17. Applicant follows this information noting the 2019 publication date is incorrect and is actually March 25, 2020 and therefore “the Webcast slides is not prior art to the instant application through the exception provided in 35 U.S.C. §102(b)(1).” with proof in a press release released March 25, 2020, see page 17 of the Remarks, 2nd para. and Miscellaneous Incoming Letter submitted December 30, 2025. Claims 3, 6, 7, 9, 14 and 16 have been cancelled.
Maintained Objection
Specification
7. The disclosure continues to be objected to because it still contains an embedded hyperlink and/or other form of browser-executable code, see page 17, lines 11, 13 and 17. The deletion of http:// does not render the hyperlink disabled except “bitincka.com/ledion/matgat”, see Amendments to the Specification submitted December 30, 2025, full paragraph, line 3. All others are still accessible and not disabled.
Applicant is requested to review the entire disclosure. 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.
New and Maintained Grounds of Rejection
Claim Rejections - 35 USC § 112
8. 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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
9. The rejection of claims 1, 4, 5, 8, 10-13, 15 and 17-20 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 maintained. Claims 3, 6, 7, 9, 14 and 16 have been cancelled.
Applicant argues “…the claimed variants of the human LAG-3 protein are sufficiently described in the specification” and “…[does] not comprise subject matter which was not described in the specification in such a way as to reasonably convent to one skilled in the art that the inventor had possession of the claimed invention at the time the application was filed.”, see Remarks submitted December 30, 2025, page 10.
Applicant’s amendment to claim 1 includes derivative thereof, soluble fragment, variant and mutant of human LAG-3 protein, all which allegedly comprise domain D1 and domain D2 of the human LAG-3 protein able to bind to MHC class II molecules.
Applicant’s amendment and arguments have been considered, however found unpersuasive.
The claim language still reads on functional attributes of the human LAG-3 protein with very little structure information that clearly informs one of skilled in the art possession of all the possibilities denoted by the derivative, fragment, mutant and variant language. The specification describes two “[e]xamples of suitable derivatives of LAG-3 protein that are able to bind to MHC class II molecules…”, noting distinct amino acid residues, see page 18, lines 3-15. These exemplary molecules are not representative of the full breadth of the human LAG-3 derivatives and it is not clear they can function as required by the claims. Hence, the rejection is maintained.
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.
The claims read on a method for preventing, treating or ameliorating a cancer comprising administering a lymphocyte activation gene-3 (LAG-3) protein or a derivative thereof which is a soluble fragment, variant, or mutant of human LAG-3 protein that comprises domain D1 and domain D2 of human LAG-3 protein and is able to bind to MHC class III molecules. The administered components, LAG-3 protein and derivative thereof is undefined, uncharacterized and may not bind MHC class II molecules, thus these broadly termed components are within a large genus. Applicant’s specification does not make clear they are in possession of all possible LAG-3 proteins or derivatives thereof of to establish possession.
At the time the application was filed Applicant does not seem to be in possession of a host of LAG-3 proteins, nor variants of LAG-3 that are able to bind MHC class II molecules. The specification seems to set forth one derivative of LAG-3, IMP321, which comprises the 30 amino acid extra-loop sequence GPPAAAPGHPLAPGPHPAAPSSWGPRPRRY (SEQ ID NO:2) of domain D1 of human LAG-3 protein and the state of the art provides “the first two N-terminal domains of soluble LAG-3 (D1 and D2) molecules, alone, are capable of binding MHC class II.”, see Huard et al. (Proc. Natl. Acad. Sci. USA 94: 5744-5749, May 1997/ IDS reference #5 on sheet 2 submitted January 23, 2025) referenced in the specification on pages 15-18.
The instant specification does not disclose or teach a genus of LAG-3 proteins, nor derivatives thereof that specifically bind MHC class II molecules. The specification does not make clear Applicant is in possession of the breadth of said components cited in the claims. No corollary nexus has been established between structure and function. There is insufficient identifying and clarifying information to support the claims with the generic embodiments.
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.
The instant application does not provide sufficient guidance as to the nexus or correlation between the structure and function of the LAG-3 proteins and derivatives thereof that places the skilled artisan in possession of the relevant identifying characteristics of a genus of derivatives that bind MHC II molecules and capable of evoking an immune response to prevent, treat or ameliorate cancer in scope with the claimed invention.
The claims here are directed to methods of using a LAG-3 protein or a derivative thereof, rather than the said components themselves, but the same standard applies with regard to the written description requirement. See University of Rochester v. G.D. Searle & Co., 358 F.3d 916, 926 (Fed. Cir. 2004):
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to that subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.
Given the highly diverse nature of imparted by the term, derivative, one skilled in the art cannot envision the structure of the LAG-3 derivative thereof by simply knowing where its binds. AbbVie establishes “[o]ne needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus.” Id.
In AbbVie v. Centocor (Fed. Cir. 2014), the Court held that a disclosure of many different antibodies (in that case neutralizing antibodies to IL-12 with a particular binding affinity) was not enough to support the genus of all IL-12 neutralizing antibodies because the disclosed antibodies were very closely related to each other in structure and were not representative of the full diversity of the genus. The Court further noted that functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support especially in technology fields that are highly unpredictable where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus.
“A sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus.” See AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69.
Vas-Cath Inc. V Mahurkar, 19 U5PQ2d 1111, clearly states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117). The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116).
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112 is severable from its enablement provision (see page 115).
The skilled artisan cannot envision the detailed structure of the encompassed antibody mimetics and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and a reference to a potential method of isolating it. The polypeptide itself is required. See Fiers v. Revel, 25 U5PQ 2d 1601 at 1606 (CAFC1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Lts. 18 U5PQ2d 1016.
Furthermore, In The Reagents of the University of California v. Eli Lilly (43 U5PQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that while Applicants are not required to disclose every species encompassed by a genus, the description of a genus is achieved by the recitation of a representative number of DNA molecules, usually defined by a nucleotide sequence, falling within the scope of the claimed genus. At section B(l), the court states that "An adequate written description of a DNA...'requires a precise definition, such as by structure, formula, chemical name, or physical properties', not a mere wish or plan for obtaining the claimed chemical invention".
At the time the application was filed Applicants seem to not be in possession of LAG-3 and all derivatives of LAG-3. The specification does not evidence the possession of all the broadly termed LAG-3 proteins and a derivative thereof that are undefined and uncharacterized falling within the potentially large genus to establish possession. No corollary nexus has been established between structure and function.
The USPTO has released a Memo on the Clarification of Written Description Guidance For Claims Drawn to Antibodies and Status of 2008 Training Materials, 02/22/2018. See https://www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf.
The Memo clarifies the applicability of USPTO guidance regarding the written description requirement of 35 U.S.C. § 112(a) concerning the written description requirement for claims drawn to antibodies, including the following.
“In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional”.
There is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the said derivatives essential to the claimed invention to demonstrate possession that fulfill the requirements of a structure-function relationships of written description. Also, see Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017).
“When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus.” See Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005).
In Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co., 94 USPQ2d 1161 (Fed Cir. 2010), the following is noted.
To show invention, a patentee must convey in its disclosure that is “had possession of the claimed subject matter as of the filing date. Demonstrating possession “requires a precise definition” of the invention. To provide this precise definition” for a claim to a genus, a patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen at page 1358).
The instant disclosure, including the claims fail to disclose a representative number of species falling with the scope of the genus and/or structural common to the members of the genus so the one of skill in the art can visualize or recognize the members of the genus of LAG-3 proteins and derivatives thereof. Likewise, the instant disclosure, including the claims fail to disclose a representative number of species falling with the scope of the genus and/or structural common to the members of the genus so the one of skill in the art can visualize or recognize the members of the genus of LAG-3 proteins and derivatives of LAG-3 protein.
Also, it is not enough for the specification to show how to make and use the invention, i.e., to enable it (see Amgen at page 1361).
An adequate written description must contain enough information about the actual makeup of the claimed products – “a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials”, which may be present in “functional terminology when the art has established a correlation between structure and function” (Amgen page 1361).
Here, Applicants’ claims include a plethora of LAG-3 proteins and derivatives thereof that encompass various structural, specificities and functional attributes to fulfill the requirements of a structure-function relationships of written description, but does not describe the structure-identifying information about the said derivatives, nor describe a representative number of species falling with the scope of the genus or structural common to the members of the genus so the one of skill in the art can visualize or recognize the member of the genus of the actual said LAG-3 protein and derivative thereof.
A skilled artisan cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus that exhibit this functional property.
The specification does not evidence the possession of all the LAG-3 proteins and derivatives thereof that are undefined and uncharacterized falling within the potentially large genus to establish possession. Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 U5PQ2d 1398.
The full breadth of the claims do not meet the written description provision of 35 U.S.C. 112, first paragraph.
10. The rejection of claims 1, 3, 4, 5, 8, 10-13, 15 and 17-20 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 maintained. Claims 3, 6, 7, 9, 14 and 16 have been cancelled.
Applicant has amended claim 1 to recite treating or ameliorating a metastatic breast cancer with human LAG-3 protein, or a derivative thereof which a soluble fragment, variant, or mutant of human LAG-3 protein that comprises domain D1 and domain 2 of human LAG-3 protein and able to bind MHC class II molecules. As stated herein, “[t]he specification has not presented evidence that a broadly termed LAG-3 protein or derivative thereof functioning in the manner suggested by the claims.” And while Applicant states the patient populations are clear, what remains unclear is whether or not the subjects with low monocytes in Figures 4 and 5, Tables 5 to 7 and the “entire patient population” of Figures 2 and 3 have metastatic breast cancer (MBC). These patient populations seem to all be treated with IMP321 and no other human LAG-3 protein, nor derivatives thereof. Accordingly, the rejection is maintained.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
Applicant's claim 1 broadly reads on a method of administering with human LAG-3 protein, or a derivative thereof which a soluble fragment, variant, or mutant of human LAG-3 protein that comprises domain D1 and domain 2 of human LAG-3 protein and able to bind MHC class II molecules to a patient with metastatic breast cancer (MBC) with one or more characteristics cited on lines 7-12 of claim 1. However, it is not clear if IMP321 (also art known as eftilagimod alpha or efti), a unique recombinant soluble LAG-3 protein or the undefined LAG-3 protein and its derivative thereof can be implemented to treat and establish an immunological response in any and all proliferative diseases. The specification has not presented evidence that a broadly termed LAG-3 protein or derivative thereof functioning in the manner suggested by the claims. At most, Figures 2-11 evidence treatment of subjects with (1) paclitaxel + placebo; (2) paclitaxel + 30mg of IMP321; and/or (3) paclitaxel + eftilagimod alpha. These Figures correspond to Results spanning pages 37-41 and 45 within the Specification filed November 28, 2022. The patient populations are not clearly set forth in the Figures and Figure captions. Example 1 on page 35 of the Specification discusses a Phase IIb clinical study in patients with HER2 negative hormone receptor-positive metastatic breast cancer and page 36 cites tumor types, Luminal A and Luminal B, however it is not clear if these are the patients represented within Figures 2-11 as the Figure captions do not clearly define the patients, except in Figures 6 and 7 (Luminal B patient); and Figures 8 and 9 (< 65 years of age). Notwithstanding, the breadth of most of the claims read on preventing and treating a host of proliferative cancers with IMP321, LAG-3 protein and a derivative, thereof.
The specification has not presented evidence of any portion, fragment of LAG-3 protein other than IMP321 (eftilagimod alpha or efti) may be capable of functioning as presented in the claims. There is no information establishing that IMP321, LAG-3 protein or derivative thereof should be regarded as a panacea for each and every cancer, as well as a preventative therapeutic agent. It is art known each cancer differs in histopathobiology, cancer biomarkers, symptoms and clinical treatment.
There is no guidance in the specification as to how to determine and select a population of individuals, which may or may not eventually have cancer. Preventing a disease is just as complex a process. It is not clear what parameters one skilled in the art would use in order to identify a population of subjects in which cancer could be prevented. It is also not clear what symptoms one of skill in the art would need to identify before possibly treating a patient. While it is art known that clinicians are capable of implementing both screening, surveillance and the type of screening test used and the intervals at which it is performed are based on risk stratification, which also serves as the basis for selecting potential candidates for possible prevention. However, like most screening procedures determining whether a population will eventually be struck with a disease is not fool proof. As stated in the Breast Cancer Fact Sheet set forth by the American Cancer Society Inc. (No. 080765, 2 pages, January 2025), “[t]here is no sure way to prevent breast cancer, and some risk factors can’t be changed,”, see page 1, Prevention segment and entire document. At this point in time and at the time of Applicant’s filing of the instant application assessing risk factors, signs and symptoms, as well as screening are the best strategies to keep cancer for possibly happening. There is lack of instruction in the specification enabling one skilled in the art to make and practice the invention commensurate within the scope of the claims utilizing the suggested therapeutic compounds.
Additionally, there is no guidance in the specification for preventing cancer and determining the appropriate time prior to the development of tumors to begin the therapy or for identifying patients at risk for developing those tumors. Cancer is not an infectious process. The specification provides insufficient guidance in regard to the issues raised above and provides insufficient working examples which would provide guidance to one skilled in the art and no evidence has been provided which would allow one of skill in the art to predict the efficacy of the claimed method in regard to all cancers with a reasonable expectation of success. In view of the above, one of skill in the art would be forced into undue experimentation to use the all suggested therapeutics of record in the claimed invention.
The broad term "cancer" encompasses several organ systems with different and distinct histopathologies and various etiologic causative agents. The claims read on embodiments that are not enabled, i.e. any cancer type and forecasting whether or not a person will develop cancer.
Granted the Office does not require that experiments under the scope of the claims produce positive and astonishing results, the experiments must be within the scope of the Forman factors (see Ex parte Forman, 230 USPQ 546, BPAI, 1986). There would also need to be some valid amount of direction or guidance, as well as presence or absence of working examples presented in the specification that would enable one skilled in the art to perform the method as presented in the recited claims.
Thus, undue experimentation would be required to implement the instantly claimed method with the said compounds. One skilled in the art would be forced into undue experimentation in order to practice the broadly claimed invention.
Furthermore, the complexity and unpredictability of the art to which the invention retains, i.e., in vivo human therapy, suggests the need for some guidance of how to effectively use the claimed methodology to achieve human therapeutic efficacy. There would also need to be some valid amount of direction or guidance, as well as presence or absence of working examples presented in the specification that would enable one skilled in the art to perform the method as presented in the recited claims. It appears that undue experimentation would be required of one skilled in the art to practice the instant claimed invention using the teachings of the specification. See Ex parte Forman, 230 USPQ 546 BPAI, 1986.
The specification provides insufficient guidance with regard to these issues and provides no working examples, which would provide guidance to one skilled in the art. For the above reasons, it appears that undue experimentation would be required to use the claimed invention.
11. 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.
12. Claims 1, 4, 5, 8, 10-13, 15 and 17-20 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.
a. Claim 1 is vague and indefinite in the recitation “…treating or ameliorating a metastatic breast cancer…comprising administering…a human LAG-3 protein, or a derivative thereof which is a soluble fragment, variant, or mutant of human LAG-3 protein that comprises domain D1 and domain D2 of the human LAG-3 protein… able to bind to MHC class II molecules” with one of six selections, see lines 1-5. However, it is not clear if only the mutant of human LAG-3 protein comprises domain D1 and domain 2 or do the human LAG-3 protein, or a derivative thereof, soluble fragment or variant also comprise the said domains. Accordingly, the metes and bounds cannot be determined.
Claim Rejections - 35 USC § 102
13. 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.
14. The rejection of claim(s) 1, 4, 5, 8, 10, 11, 13, 15 and 18-20 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 3, 6, 7, 9 and 14 have been cancelled.
Applicant argues their amendments to claim overcome the instant rejection, see Remarks submitted December 30, 2025, bridging pages 12 and 13.
Applicant recites the criteria required for a proper anticipatory rejection and state the teachings of the prior art, Brignone, see page 13, 1st and 2nd paragraphs (paras.). Applicant follows with all Brignone does not allegedly disclose, nor teach, see pages 12 and 14.
Applicant’s arguments and points of view have been carefully considered but fail to persuade.
Applicant’s amendment to claim 1 cites “wherein the subject is selected from one or more of:”, see lines 5 and 6. Therefore, from the six (6) requirements only one is required to anticipate the claim.
Notwithstanding, Brignone teaches the patients had a low monocyte count and “…the normal range for monocytes is 0.3 - 0.8 × 109 CD45+CD14+ cells/l whole blood”, see page 7, last sentence in column (col.) 2. 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 subjects of Brignone are within the range of age of less of than about 65 years and some of the patients did not have taxane chemotherapy, see page 2, Table 1. The LAG-3 protein, IMP321 is administered with and after paclitaxel, see Figure 1 on page 3. Hence, the rejection does not fall for the reasons cited herein and of record. The rejection is maintained.
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, were within an age range between 47-78 years of age, 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. The median age of the patient was 64 years of age, see page 2, Table 1.
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 on page 4; Figure 4 on page 7; and page 10, 1st full paragraph.
15. The rejection of claim(s) 1, 4, 5, 8, 10-12 and 17-20 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 3, 6, 7, 9 and 16 have been cancelled.
Applicant argues their amendments to claim overcome the instant rejection, see Remarks submitted December 30, 2025, bridging pages 12 and 13.
Applicant recites the teachings of the prior art, Dirix, see pages 14 and 15. Applicant follows with all Dirix does not allegedly disclose, nor teach, see pages 15.
Applicant’s arguments and points of view have been carefully considered but fail to persuade.
Applicant’s amendment to claim 1 cites “wherein the subject is selected from one or more of:”, 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 page 1968, last sentence bridging page 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 paragraph. Luminal B breast cancer is hormone receptor positive/HER2 positive. Hence, the rejection does not fall for the reasons cited herein and of record. The rejection is maintained.
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.). The patients were at least 18 years of age, see page 1868, Key…segment.
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.
16. Claim(s) 1, 4, 5, 8, 10-13 and 17-20 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Strum et al., WO 2020/037251 A1 (effective filed 16 August 2019). 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 KI67-positive (KI67+). In one embodiment, the ER+ breast cancer is KI67-negative (KI67-). 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.
Conclusion
17. 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.
18. 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.
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ALANA HARRIS DENT
Primary Examiner
Art Unit 1643
20 March 2026
/Alana Harris Dent/Primary Examiner, Art Unit 1643