DETAILED ACTION
Examiner acknowledges receipt of applicant’s reply filed 12/01/2025, in response to the non-final office action mailed 8/06/2025.
Claims 1, 4, 5, 7-9, 11, 13-19, 21-26, 28-33, 43, 44 and 46-63 are pending. Claims 3 and 27 have been cancelled. Claims 19, 21-23, 30, 32, 33, 43, 44, and 47-63 remain withdrawn for the reasons made of record.
Claims 1, 4, 5, 7-9, 11, 13-18, 24-26, 28, 29, 31, and 46 are being examined on the merits in this office 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 .
Examiner Comment
Claim 27 was improperly amended to cancel the claim. Cancelled claims should only have the claim number and status identifier, without any text.
Improper:
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27. (Cancelled)
Claim Objections- withdrawn
The objection of claims 1, 3, 4, 7, 11, 14-16, 18, 24, 26, and 28 is withdrawn in view of the amendment filed 12/01/2025.
Claim Rejections - 35 USC § 112- withdrawn
The rejection of claims 1, 3-5, 24-29, 31, and 46 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of the amendment filed 12/01/2025.
Response to Arguments
Applicant's amendment and arguments, filed 12/01/2025, with respect to the above objections and rejections have been fully considered and are persuasive. objections and rejections have been withdrawn.
Applicant's arguments filed 12/01/2025 have been fully considered but they are not persuasive with respect to the maintained rejection.
Upon further consideration, a new ground(s) of objection is made in view of the amendment filed 12/01/2025.
An action on the merits is set forth herein.
Specification
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
Maintained Rejections
Claim Rejections - 35 USC § 112
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.
Claims 1, 4, 5, 7-9, 11, 13-18, 24-29, 31, and 46 remain/are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This rejection is maintained from the office action mailed 8/6/2025, but has been amended to reflect claims filed 12/01/2025.
The courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP 2163.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co., the court stated:
“A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials. Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284-85 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus. . . ."). Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gostelli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618.
In the instant case, the claims are drawn to an antibody conjugate comprising an antibody, or antigen- binding fragment thereof, covalently linked to a drug payload and wherein the antibody, or antigen-binding fragment thereof, is further covalently linked to an immunomodulatory payload, wherein the drug payload is a cytotoxic compound, wherein the immunomodulatory payload is an agonist of the STING (stimulator of interferon genes) pathway, and wherein the cytotoxic compound is selected from the group consisting of an alkylating agent, DNA-crosslinking agents, anti-tumor antibiotics, anti-metabolites, anti- mitotic agents, microtubule disrupting agents, histone-deacetylase (HDAC) inhibitors, telomerase inhibitors and immunogenic cell death agents.
The specification does not explicitly define the terms “drug payload”, or “agonist of the STING (stimulator of interferon genes) pathway”. Claim 26 recites a Markush grouping of cytotoxic compounds, e.g. including but not limited to, carboplatin, chlorambucil, docetaxel and a hemiasterlin. Claim 4 recites wherein the agonist of the STING pathway is ulevosting, 1R,6R,8R,9R,10S,15R,17R,18R)-8,17-bis(6-aminopurin-9-yl)-12-oxido-3-oxo- 12-sulfanylidene-3-sulfido-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5- diphosphatricyclo[ 13.2.1.06,10]octadecane-9,18-diol,or SB11285. The specification is limited to disclosure of 4 STING agonists - MK-1454 (Merck), ADU-S100 (Aduro), TTI-10001 (Trillium Therapeutics), and SB11285 (Springbank Pharmaceuticals) (para. [0500]).
Agonists of the STING pathway are construed as encompassing any compound that directly or indirectly affects the STING pathway. Compounds could be construed as encompassing but not limited to, small molecules, antibodies, peptides, proteins, and any combination thereof.
No examples of a claimed antibody conjugate comprising an antibody, or antigen- binding fragment thereof, covalently linked to a cytotoxic compound (drug payload), and an agonist of the STING (stimulator of interferon genes) pathway (immunomodulatory payload) was reduced to practice.
As stated earlier, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable claims 1, 4, 5, 7-9, 11, 13-18, 24-29, 31, and 46 are broad generics with respect to all possible compounds encompassed by the claims. There are numerous compounds that can fall within the categories of “drug payload” and “agonist of the STING (stimulator of interferon genes) pathway” but there is no guidance as to what specific compounds can physically be combined with each other to form the claimed antibody conjugates while retaining individual functional properties.
It must not be forgotten that the MPEP states that if a compound is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. Here, though the claims may recite some functional characteristics [e.g., anchor peptide], the claims lack written description because there is no disclosure of a correlation between function and structure of the compounds beyond compounds disclosed in the examples in the specification. Moreover, the specification lacks sufficient variety of species to reflect this variance in the genus.
Examiner reiterates that no embodiments of the claimed invention were reduced to practice. There are no examples of an antibody conjugate comprising an antibody, or antigen- binding fragment thereof, covalently linked to a cytotoxic compound (drug payload), and an agonist of the STING (stimulator of interferon genes) pathway (immunomodulatory payload) was reduced to practice.
The specification appears to be limited to a listing compounds that fall within the claim scope of cytotoxic compounds and agonist of the STING pathway. The specification doesn’t provide any examples that encompass the numerous characteristics of the entire genus claimed.
It is further noted that the prior art taught that STING agonists were highly selective. Preclinical studies using the agent 5,6- dimethyllxanthenone-4-acetic acid (DMXAA) showed potent anti-tumor activity in various mouse models. However, this agent showed no effect in the clinic when combined with chemotherapy in a Phase III trial in human non-small cell lung cancer. DMXAA can only interact with the murine molecule. This likely explains the lack of clinical activity of this compound in human cancer patients, and prompted the development of new agents that might serve as direct human STING agonists. At the same time, it has become apparent that the human TMEM173 (STING gene) is polymorphic, and natural CDNs do not stimulate all human STING variants (Corrales et al (Cytokine 77:245-247 (2016) at p. 2- previously cited). Thus, the skilled artisan would have known that although a compound may be a “STING agonist” it would have limited functionality with respect to i) Ab (mouse Ab and human specific STING agonist combination), or ii) the animal species to which the claimed antibody conjugate was administered.
Merely listing components in the specification is not sufficient to extrapolate to all combinations of antibodies/antigen binding fragments, cytotoxic compounds, and STING agonists that are not only capable of being fused together but further retain their functional binding/targeting to the STING pathway and cytotoxic effects.
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"). Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Response to Arguments
Applicant traversed the rejection at pp. 21-22 of the reply filed 12/01/2025. Applicant asserts that claim 1 has been amended to incorporate claim 3 [Markush grouping of categories of cytotoxic compounds]. Applicant further asserts that “one skilled in the art would readily understand the term [agonist of STING pathway] based on the support found in paragraph [00500] that lists STING agonists. [The specification discloses four STING agonists]. Applicant states “the agonist of STING in claim 1 is characterized by the structure of the antibody conjugate” (reply at p. 21). Applicant asserts that actual reduction to practice is not necessary and that the written description requirement can be satisfied through description and drawings. Id. Applicant argues that the specification discloses immune stimulatory antibody-drug conjugates (iADCs) that aren’t dual conjugates of antibodies with STING agonists and cytotoxins. The antibody recognizes a “suitable antigen” covalently linked directly or indirectly to payloads, e.g. agonist of STING (reply at p. 22). Applicant asserts that while there is no specific data for a STING conjugate, their support for iADCs of two therapeutic agents in disclosure of 4 agonists of the STING pathway. Id. Applicant asserts that the skilled artisan would conclude the inventor had possession of the claimed antibody conjugates based on the disclosed empirical data of the specification. Id.
Examiner has reviewed and considered Applicant’s arguments but is not persuaded.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. In the instant case, the disclosure does not provide any examples that are representative of the genus of antibody conjugates. The disclosure of 4 agonists of STING in a single paragraph of the specification that is 270 pages in length is not representative of the entire genus because the instant claims are extremely broad and encompasses a huge genus of antibody conjugates.
Examiner reiterates that the specification is limited to disclosure of 4 STING agonists - MK-1454 (Merck), ADU-S100 (Aduro), TTI-10001 (Trillium Therapeutics), and SB11285 (Springbank Pharmaceuticals) (para. [0500]). Agonists of the STING pathway are construed as encompassing any compound that directly or indirectly affects the STING pathway. Compounds could be construed as encompassing but not limited to, small molecules, antibodies, peptides, proteins, and any combination thereof.
The art further indicates that STING agonists were highly selective. Preclinical studies using the agent 5,6- dimethyllxanthenone-4-acetic acid (DMXAA) showed potent anti-tumor activity in various mouse models. However, this agent showed no effect in the clinic when combined with chemotherapy in a Phase III trial in human non-small cell lung cancer. DMXAA can only interact with the murine molecule. This likely explains the lack of clinical activity of this compound in human cancer patients, and prompted the development of new agents that might serve as direct human STING agonists. At the same time, it has become apparent that the human TMEM173 (STING gene) is polymorphic, and natural CDNs do not stimulate all human STING variants (Corrales et al (Cytokine 77:245-247 (2016) at p. 2- previously cited). Thus, the skilled artisan would have known that although a compound may be a “STING agonist” it would have limited functionality with respect to i) Ab (mouse Ab and human specific STING agonist combination), or ii) the animal species to which the claimed antibody conjugate was administered.
As noted by Applicant, the claimed antibody conjugates comprise an antibody that recognizes a “suitable antigen”- which further imparts variability and complexity to the instant claim scope because the target antigens are not expressly defined. The corresponding antibody sequence(s) are also unknown. The categories of cytotoxic compounds recited in claim 1 encompass numerous specific chemicals and compounds.
The individual components of the claimed antibody conjugates are extremely broad and encompasses many different antibody and/or antigen binding fragments, cytotoxic compounds, and immunomodulatory payloads (agonists of the STING pathway). The instant claim scope encompasses an infinite number of combinations thereof to arrive at the claimed antibody conjugates. However, the specification does not disclose any representative of the entire diverse genus. There is no guidance as to what specific compounds can physically be combined with each other to form the claimed antibody conjugates while retaining individual functional properties.
For the reasons presented above, the rejection is maintained.
New Objection
Claim Objections- New
Claims 1 and 26 are objected to because of the following informalities: this objection is necessitated by the amendment filed 12/01/2025.
Claim 1 should be amended to recite the compounds in singular format, instead of presently written plural, e.g., a DNA-crosslinking agent an anti-tumor antibiotic
Claim 26 should be amended to recite “the cytotoxic compound is selected”.
Appropriate correction is required.
Relevant Art Not Relied Upon
Bruml et al (WO2018/200812, published Nov 2018- previously cited) teach immunoconjugates comprising an antibody, or a functional fragment thereof, linked to a STING agonist via a linker. The antibody, or functional fragment thereof, can be engineered to include a non-naturally occurring amino acid, e.g., para-acetyl Phe or para-azido-Phe, which is reacted with the linker component of the immunoconjugates. The immunoconjugates can be combined with a pharmaceutically acceptable carrier or excipient, and with one or more additional therapeutic agents, and then administered to a patient in order to treat cancer.
Bruml et al do not teach or suggest that an immunoconjugate comprises a cytotoxic compound linked to the Ab-STING agonist. The reference does not teach or suggest an antibody conjugate comprising three distinct elements: Ab, STING agonist, and drug payload (cytotoxic compound).
Thompson et al (U.S. 20170158772- previously cited) teach compositions of antibody construct-immune stimulatory compound conjugates (abstract). The antibody construct comprises an antigen binding domain and an Fc domain. The immune stimulatory compound can be a STIN agonist (e.g., para. [0066], [0173]).
Thompson et al do not teach or suggest that an immunoconjugate comprises a cytotoxic compound linked to the Ab-STING agonist. The reference does not teach or suggest an antibody conjugate comprising three distinct elements: Ab, STING agonist, and drug payload (cytotoxic compound).
U.S. Patent No. 11,744,876- previously cited, which issued based upon parent application 16/898,233, has been carefully considered; however, the claims of the ‘876 patent do not raise issues of non-statutory double patenting with the instant claims. The claims of the ‘876 patent do not recite STING agonists.
Conclusion
No claims are allowed.
Claims 1, 4, 5, 7-9, 11, 13-19, 21-26, 28-33, 43, 44 and 46-63 are pending. Claims 19, 21-23, 30, 32, 33, 43, 44, and 47-63 are withdrawn.
Claims 1, 4, 5, 7-9, 11, 13-18, 24-26, 28, 29, 31, and 46 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTINA M HELLMAN whose telephone number is (571)272-2836. The examiner can normally be reached M-F 9:00 am-5:30 pm.
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/KRISTINA M HELLMAN/ Examiner, Art Unit 1654
/JULIE HA/ Primary Examiner, Art Unit 1654