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 Amendments and Arguments
2. Claims 22, 23, 25-28, 30, 31, 33, 34, 36, 38, 48, 49, 52-54, 56-58, 60 and 62 are pending.
Claims 26-28, 30, 31, 33, 34, 36, 38, 48, 49, 52-54, 56-58 and 60, drawn to non-elected inventions and non-elected species are not examined on the merits.
Claims 22, 23, 27, 28 and 62 have been amended.
Claims 22, 23, 25 and 62 are examined on the merits with species (tumor): tumors of the skin (including melanoma).
New and Maintained Grounds of Rejection
Claim Rejections - 35 USC § 112
3. 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.
4. The rejection of claims 22, 23, 25 and 62 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.
Applicant asserts “the specification adequately identifies the structural properties required for retaining antigen/ligand binding and consequently the required function, e.g. at [page]p.17 [line]1. 9-23. In addition, as indicated above, the claims now explicitly recite the structural features of containing a SLAMF6- or LAG3-binding fragment. Accordingly, it is respectfully submitted that the claims as amended meet the written description requirement.”, see Remarks submitted August 14, 2025, paragraph (para.) bridging page 7 and 8.
Applicant’s arguments and disclosure have been carefully considered, but fails to persuade.
While Applicant states and points out within their specification alleged support and evidence for structural properties, this information does not describe the structure-identifying information about the soluble SLAMF6- ectodomain polypeptides, anti-SLAMF6 antibodies, analogs containing a SLAMF6-binding fragment thereof, soluble LAG3 polypeptides, anti-LAG3 antibodies and analogs containing a LAG3-binding fragment thereof. These molecules have not been identified or characterized by structure, nor function. While these therapeutic agents are intended to functionally facilitate treatment, there is no description of the structure-identifying information. Applicant does not describe a representative number of species falling within the scope of the genus or structural common feature(s) to the members of the genus so one of skill in the art can visualize or recognize the members of the genus of the actual listed SLAMF6-mediated T cell activators and LAG3 inhibitors themselves. Accordingly, the specification does not adequately describe a representative number of members of the genus or provide a written description of the genus comprising a host of listed SLAMF6-mediated T cell activators and LAG3 inhibitors. Applicant has not pointed to any specific evidence within the disclosure that describes the activators and inhibitors as required by the test set forth in Ariad.
The specification does not make clear Applicant are in possession of all the possible binding molecules that are undefined and uncharacterized falling within the potentially large genus to establish possession. No corollary nexus has been established between structure and function. There is insufficient to support the generic claims. Accordingly, 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 pharmaceutical composition, as well as a pharmaceutical pack comprising therapeutically effect amounts of a signaling lymphocyte activation molecule family member 6 (SLAMF6)-mediated T cell activator and a lymphocyte activation gene 3 (LAG3) inhibitor. SLAMF6-mediated T cell activators read on “…soluble SLAMFG6 ectodomain polypeptides, including isolated ectodomains of SLAMF6 isoforms (e.g. SLAMFG6 splice variants 1-4), and other SLAMF6 ligands (e.g. antibodies) that are functional mimetics (analogs) thereof, capable of enhancing T cell activation or exhibiting other immune-enhancing biological activities mediated by an isolated SLAMF6 ectodomain,”, see paragraph bridging pages 5 and 6. Not only are the analogs designated as functional mimetics, but also include “…functional and structural mimetics of said polypeptides and antibodies,”, see page 16, 3rd paragraph. These SLAMF6-mediated T cell activators and analogs thereof are contained within a pharmaceutical composition with a LAG3 inhibitor, see Pharmaceutical compositions section spanning ges 18-21.
“LAG3 inhibitors to be used in embodiments of the invention may include LAG3-specific neutralizing (blocking) antibodies, and other LAG3 ligands having LAG3 antagonistic activity, including, but not limited to soluble LAG3 polypeptides (e.g. soluble LAG3-Ig fusion proteins). For example, without limitation, LAG3 inhibitors may include IMP321, BMS-986016 (relatlimab), LAGS525, REGN3767, TSR-033 and combinations thereof. In other embodiments, the use of small molecules and nucleic acid agents, such as small molecule LAG3 inhibitors and LAG3-downregulating nucleic acids (e.g. antisense or siRNA oligonucleotides) is contemplated.”, see page 6, 1st paragraph.
Hence, the written description in this instant case reads on a plethora of SLAMF6-mediated T cell activators including a host of ectodomain polypeptides, anti-SLAMF6 antibodies and analogs thereof, as well as a host of LAG3 inhibitors.
The written description is not commensurate in scope with vast molecules that can be regarded as a SLAMf6-mediated T cell activator and a LAG3 inhibitor. The instant application does not provide sufficient guidance as to the nexus or correlation between the structure and function of an undefined host of SLAMF6-mediated T cell activator molecules and LAG3 inhibitor molecules that are combined to render a therapeutic effect. These facts do not place the skilled artisan in possession of the relevant identifying characteristics of a genus of both sets of molecules.
The specification has not described sufficient structural limitations, coupled with functional, which provide guidance on the identification of any of these molecules.
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.
Vas-Cath Inc. V. Mahurkar, 19 USPQ2d 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 antibodies 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 USPQ 2d 1601 at 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Lts. 18 USPQ2d 1016.
Furthermore, In The Reagents of the University of California v. Eli Lilly (43 USPQ2d 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(1), 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 did not have possession of the breadth of SLAMF6-mediated T cell activators and LAG3 inhibitors. The specification does not evidence the possession of all the possible molecules that fall under the breadth of the broad terms, SLAMF6-mediated T cell activator and LAG3 inhibitor. These molecules are undefined and uncharacterized and fall within a potentially large genus to establish possession.
No corollary nexus has been established between structure and function for the plethora of SLAMF6-mediated T cell activator inclusive of a host of molecules, as well as a plethora of LAG3 inhibitors inclusive of a host of molecules. Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 USPQ2d 1398.
The full breadth of the claims do not meet the written description provision of 35 U.S.C. 112, first paragraph.
5. 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.
6. The rejection of claims 22, 23, 25 and 62 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 pre-AIA the applicant regards as the invention is maintained and made.
Applicant notes “it is believed that the rejection has been overcome” because they cite wherein the specification, the term "analog" has been defined and wherein the structural and functional properties characterizing said analogs, see Specification, p. 16, l. 25-26; p. 16, l. 27 to p. 17, l. 23, see Remarks submitted August 14, 2025, page 8, 4th paragraph (para.).
Moreover, Applicant states claims [examined claim 62] “were amended to explicitly recite the inclusion of a SLAMF6- or LAG3-binding fragment, as suggested…claim 23 as amended does not recite the phrase in question.”, see Remarks, page 8, 4th para.
Applicant’s arguments and points of view have been carefully considered, but fail to persuade.
Lines 25 and 26 on page 16 of the Specification reads “the use of analogs including functional and structural mimetics of said polypeptides and antibodies, is contemplated.” This information does not define the analogs and does cure the indefiniteness of the claims. The Examiner suggested the deletion of the term, analogs and replacing the term with the phrase, antigen binding fragment thereof.
a. While claim 23 no longer recites “analogs thereof”, newly amended claims 22 and 62 recite “…analogs containing a [protein X] binding fragment thereof”. It remains unclear how an analog molecule is similar or analogous to a binding fragment thereof. It is also not clear how an analog has a binding fragment thereof within it. Applicant is requested to clarify. Once of ordinary skill in the art cannot determine the metes and bounds.
Claim Rejections - 35 USC § 103
7. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
8. 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.
9. The rejection of claim(s) 22, 23, 25 and 62 under 35 U.S.C. 103 as being unpatentable over Dranoff et al., WO 2017/019894 (published 2 February 2017/ IDS reference 12 on sheet 5 submitted May 10, 2022), and further in view of Yigit, Haliboze, et al. (Oncotarget 7(18): 26346-26360, published March 25, 2016) referenced herein as YH and Yigit et al., (Clinical Immunology 204: 3-13, available online 23 October 2018/ IDS reference #5 submitted August 7, 2023) is maintained.
Initially, Applicant states “[n]one of the cited publications, either alone or in combination, should be deemed to teach or suggest the claimed invention. Applicant further submits that one of ordinary skill in the art would not have been motivated to combine these publications, which are directed to distinct therapeutic problems and solutions, and that, even if combined, would not have led the skilled artisan to arrive at the claimed invention. Further, as disclosed in the specification as filed, the claimed combinations exhibit remarkable and unexpected synergistic activity, that could not have been envisaged prior to the present invention”, see Remarks submitted August 14, 2025, page 9, Applicant’s Response.
Applicant continues Remarks continually stating the alleged deficiencies of primary reference, Dranoff, as well as the secondary references do not remedy the alleged misgivings of Dranoff, see Remarks, paragraph bridging pages 9 and 10 and pages 10-12. In particular, Applicant avers Dranoff has long lists of components and there is no “…direction or motivation… to select the particular combination of active ingredients…, see lines 1-4 on page 10. The antibodies of YH do not disclose the anti-SLAMF6 antibody as a T cell activator, but rather “…designed to eliminate (rather than to activate) SLAMF6-expressing cells”, see page 10.
The remainder of Applicant’s Response discuss why the skilled artisan would not have been motivated combine the Dranoff and YH publications without detailing the alleged deficiencies of Yigit, see pages 10 and 11.
Applicant point out teachings within their Specification, noting there is a surprising discovery, “…cancer treatment was…demonstrated in a series of experiments, showing a synergistic effect of targeting SLAMF6 and LAG3 in combination…” and there are unexpected results, see pages 11 and 12.
Applicant’s arguments, points of view and passages noted in the Response where carefully considered, but found unpersuasive.
Foremost, Applicant’s claimed invention reads on a product and not a method, wherein a clinical outcome, desired result or effect and treatment endpoint would be significant. Each reference teaches a product to be administered, as well as impetus to combine the products.
Contrary, to Applicant’s initial argument, Dranoff teaches an effector cell combination including “…an immunomodulator (e.g., one or more of: an activator of a costimulatory molecule or an inhibitor of an immune checkpoint molecule as described herein).”, see page 8, lines 1-3. Therein, it is plainly stated “the effector cell combination includes a T cell modulator chosen from an inhibitor of a checkpoint inhibitor (e.g., an inhibitor of one or more of: … LAG-3, …,” the inhibitor of the checkpoint inhibitor is an antibody molecule (e.g., a mono- or bispecific antibody or fragment thereof as described herein. the inhibitor of the checkpoint inhibitor is an antibody molecule against … LAG-3, … or any combination thereof (e.g. a combination as described herein). And “the effector cell combination includes a T cell modulator chosen from an agonist or an activator of a costimulatory molecule. In one embodiment, the agonist of the costimulatory molecule is chosen from an agonist (e.g., an agonistic antibody or antigen-binding fragment thereof, or a soluble fusion) of … SLAM (e.g., SLAMF7),…, see page 8, lines 4-16.
“[C]ombinations can be administered together in a single composition” for the benefit of treating cancerous or infection disorders, see Dranoff page 12, last paragraph; Uses…beginning on page 34; and entire document.
The teachings of the three prior art documents reasonably establish motivation to combine the two active ingredients within a pharmaceutical composition and a pharmaceutical pack. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). In re Kerkhoven supports the Examiner's position, one of ordinary skill in the art would have been motivated to combine these two therapeutic agents. In view of the combination of references, it is clear these references are sufficient in establishing the bases of the pending 103 rejection utilizing Dranoff and the additional secondary references are complementary and proper.
Applicant cites a specific antibody, which is of record in YH on page 26357 and according to Applicant’s statement is directed to a non-activating SLAMF6 epitope and unable to stimulate T cells, see page 10 of the Remarks, paragraphs (paras.) 1 and 2. However, based on the claim language, the anti-SLAMF6 antibody is presupposed to act in the manner Applicant assert it does not. “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id., see MPEP 2112.01. Accordingly, the rejection is maintained.
Dranoff teaches a combination of therapeutic agents that enhance an effector cell response (referred to herein as an “effector cell combination”), see page 7 of the paragraph (para.) bridging page 8; and page 12, 2nd para. “[T]he effector cell combination includes an immunomodulator (e.g., one or more of: an activator of a costimulatory molecule or an inhibitor of an immune checkpoint molecule as described herein). In some embodiments, the effector cell combination includes a T cell modulator chosen from an inhibitor of a checkpoint inhibitor … LAG-3,… e.g., an inhibitor of LAG-3 and PD-1, or an inhibitor of LAG-3 and TIM-3). In one embodiment, the inhibitor of the checkpoint inhibitor is an antibody molecule (e.g., a mono- or bispecific antibody or fragment thereof as described herein).”, page 8.
“[A]n inhibitory nucleic acid (e.g., a dsRNA, siRNA or shRNA), can be used to inhibit expression of an inhibitory molecule. In other embodiments, the inhibitor of an inhibitory signal is, a polypeptide e.g., a soluble ligand (e.g., PD-1-Ig or CTLA-4 Ig), or an antibody or antigen-binding fragment thereof, that binds to the inhibitory molecule; e.g., an antibody or fragment thereof (also referred to herein as “an antibody molecule”) that binds to … LAG-3,”, see para. bridging pages 14 and 15.
“In some embodiments, the effector cell combination includes a T cell modulator chosen from an agonist or an activator of a costimulatory molecule. In one embodiment, the agonist of the costimulatory molecule is chosen from an agonist (e.g., an agonistic antibody or antigen-binding fragment thereof, or a soluble fusion) …, SLAM (e.g., SLAMF7),.”, page 8.
“The combinations disclosed herein can be administered together in a single composition or administered separately in two or more different compositions, e.g., compositions or dosage forms as described herein. The administration of the therapeutic agents can be in any order. The first agent and the additional agents (e.g., second, third agents) can be administered via the same administration route or via different administration routes. For example, a first therapeutic agent can be administered concurrently with, prior to, or subsequent to, the additional agent.”, page 12, last paragraph bridging page 13; paragraph bridging pages 44 and 45; and page 56, last full para.
Therapeutic kits include a combination of therapeutic agents and instructions for use, see page 5, 2nd para.; page 52, 2nd para.; and page 206, 2nd para. It is within the purview of the Examiner that the taught therapeutic kit is synonymous with Applicant’s pharmaceutical pack.
Dranoff does not explicitly teach the pharmaceutical composition comprising the LAG3 inhibitor and SLAMF mediated T cell activator, that is SLAMF6.
However, YH teaches a combination of an anti-SLAMF6 antibody (aSlamf6) with an additional anticancer therapeutic, ibrutinib, see page 26346 and the entire reference.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of both references to combine the therapeutic binding molecules of Dranoff that specifically bind to LAG3 with an anti-SLAMF6 antibody of YH. In addition, Dranoff teaches an effector cell combination including an inhibitor of LAG-3, as well as an agonist of a costimulatory molecule (e.g., an agonistic antibody or antigen-binding fragment thereof, or a soluble fusion) including a member of the SLAM family of cell surface receptors, see page 8; and para. bridging pages 58 and 59.
One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by teachings in Dranoff that combination therapies can be easily combined, packaged together and assembled for the treatment or diagnosis of diseases and YH successfully combined aSlamf6 with another therapeutic agent to treat chronic lymphocytic leukemia (CLL), see all references in their entireties. Moreover, Yigit teaches “…SLAMF6 can be exploited as a target in human malignancies” as “[it] is expressed on a wide variety of immune cells” and has high expression in various B cell lymphomas, see page 3, Introduction, last sentence; and page 5, segment 3.1, 2nd para.
Conclusion
10. 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.
11. 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 on 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 on 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
/Alana Harris Dent/Primary Examiner, Art Unit 1643
27 October 2025