DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 3, 10 and new claims 20-22 and 24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 16, 2025.
Claims 1, 4, 6-7, 9, 12, and new claims 15-19 and 23 are under consideration in this office action.
Withdrawn Rejections
Any rejection of record pertaining to cancelled claims 2, 5, 8, and 11 is rendered moot by applicant' s cancellation of said claim.
The rejection of claims 1, 3-4, 6-7, 9 and 12 under 35 U.S.C. 112(b) for being indefinite are withdrawn in view of applicant’s amendment.
The rejection of claim 1 under 35 U.S.C. 102(a)(1) as being anticipated by Bottcher et al is withdrawn in view of applicant’s amendment to limit the composition to one comprising at least one polyamine.
The rejection of claims 1, 4, 6-7, 9, and 12 under 35 U.S.C. 102(a)(1) as being anticipated by CN106399380 is withdrawn in view of applicant’s amendment. Applicant’s arguments with respect to the claims have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on January 13, 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS is being considered by the examiner.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
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.
Claim 9 is 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.
Claim 9 recites that “the pharmaceutical composition is used as an anti-cancer agent, an anti-infective agent or a combination thereof” without any active, positive steps delimiting how the method is actually practiced. Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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, 6-7, 9, 12, and new claims 15-19, and 23 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 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.
-New matter
Amended claim 1 and new claim 15 include the limitation wherein the polyamine is “isolated spermidine”. It is noted that “isolated spermidine” does not appear within the specification as filed. Rather, the specification discloses the polyamines spermidine, spermine, putrescine, and salts thereof (pg 2). Thus, the limitation of isolated spermidine is not supported by the specification.
MPEP § 2163.05 discusses changes to the scope of the claims, and states, “The failure to meet the written description requirement of 35 U.S.C. 112, first paragraph, commonly arises when the claims are changed after filing to either broaden or narrow the breadth of the claim limitations, or to alter a numerical range limitation or to use claim language which is not synonymous with the terminology used in the original disclosure.” To comply with the written description requirement of 35 U.S.C. 112(a) or to be entitled to an earlier priority date or filing date under 35 U.S.C. 119, 120, or 365(c), each claim limitation must be expressly, implicitly, or inherently supported in the originally filed disclosure. By adding the limitation of isolated spermidine, applicant is attempting to alter the scope of the claims. Because the instant claims now recite a limitation that was not clearly disclosed in the specification as filed, new concepts have been introduced, which violates the description requirement of the first paragraph of 35 U.S.C. 112. To obviate the instant rejection of record, Applicant is invited to provide sufficient written support for the new limitation indicated above. See MPEP 714.02 and 2163.06.
-Inhibitor of PD-1 signaling, including antibodies
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the 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. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
Claims 4, 6-7, 9, 12, and new claims 15-19, and 23 are directed to a pharmaceutical composition comprising an inhibitor of PD-1 signaling. This genus encompasses an unknown number of possible agents, including antibodies. As such, the inhibitors and antibodies are defined entire by function, e.g., inhibition of PD-1 signaling or binding to PD-1, PD-L1, or PD-L2.
Antibodies generally share certain characteristics such as Fc regions or hinge regions. However, these structures are not correlated with the binding function of the antibody. It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three complementarity determining regions (CDRs) that provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity, which is characteristic of the immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences, which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (see Almagro et al, Section 3 “Antibody Structure and the Antigen Binding Site” and Figure 1; PTO-892 from 9/8/2025).
There is no way to a priori look at an antigen sequence (e.g., PD-1 or PD-L1) and envisage the combination of six CDRs that will bind that antigen. First, even highly related CDRs may not bind the same target. See for example Kussie (PTO-892 from 9/8/2025), who demonstrates that a single amino acid change in the heavy chain of an antibody that binds p-azophenylarsonate (Ars) completely abrogates the ability of the antibody to bind Ars but adds the functionality of binding the structurally related p-azophenylsulfonate (see abstract). Second, even when provided with several related antibodies that bind the desired target, this does not represent the astronomical and potentially unknowable breadth of all possible amino acid sequences which will result in the desired binding properties. This is exemplified by the Court decision in Abbvie (Abbvie v Janssen 759 F.3d 1285 (Fed. Cir. 2014)), where Abbvie developed over 200 antibodies that shared 99.5% identity in the variable regions (pg 7) and which bound the target, but in no way allowed one to envisage the unique structure of Centocor’s antibodies which bound the same target but shared only 50% sequence similarity (see table on pg 11).
While the prior art teaches some understanding of the structural basis of antigen-antibody recognition, it is noted that the art is characterized by a high level of unpredictability, since the skilled artisan still cannot accurately and reliably predict the consequences of amino acid substitutions, insertions, and deletions in the antigen-binding domains.
The specification provides no examples of PD-1 inhibitor or anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody. The specification does not provide adequate written description for the entire claimed genus of PD-1 pathway inhibitor, because one skilled in the art would be unable to immediately envision, recognize, or distinguish most of the members comprised within the genus claimed, specifically, for the antibodies, which heavy chain and light chain amino acid sequences should be combined to yield an antigen-binding region that is capable of binding PD-1, PD-L1, or PD-L2.
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.
In the instant case, the specification provides insufficient direction or guidance concerning the relationship between the structure of the possible antibody to demonstrate possession of the breadth of the genus of PD-1 pathway inhibitors, especially in view of the unpredictability of such an endeavor. The prior art, as evidenced by Edwards et al., 2003 (PTO-892 from 9/8/2025), teaches there is a substantially huge antibody diversity produced to one single antigen target. Edwards provides evidence that over 1000 antibodies, all different amino acid sequences, were generated towards one single protein antigen target (see abstract). Without a correlation between structure and function, the claims do little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function … does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
To provide adequate written description and evidence of possession of the claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In the instant case, the only factors present in the claims are a recitation of two broad genera that encompass a diverse and huge number of possible antibodies and other agents that bind the disclosed epitope. The specification does not provide a consistent structure for all of the possible antibodies and fails to provide a representative number of species for the claimed genus. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.
For claims drawn to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., high affinity, neutralization activity, competing with a reference antibody for binding), “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011). An antibody described only by functional characteristic, such as antibody that binds IL-1b or IL-6, without any known or disclosed correlation between that function and the structure of the sequence, is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the biomolecule of interest. In re Bell, 991 F.2d 781, 26 U.S.P.Q.2d 1529 (Fed. Cir. 1993). In re Deuel, 51 F.3d 1552, 34 U.S.P.Q.2d 1210 (Fed. Cir. 1995).
With the exception of specifically disclosed antibodies, the skilled artisan cannot envision the detailed chemical structure of all of the encompassed antibodies, and therefore conception is not achieved until reduction to practice has occurred. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class. 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 1115).
Therefore, claims 1, 4-9, and 11-12 do not meet the written description requirement.
Claim Rejections - 35 USC § 102(a)(2)
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)(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.
Claims 1, 4, 6-7, 9, 12, and new claims 15-19 and 23 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by US 20210030703, filed March 11, 2019 (“Kroemer”; instant PTO-892).
The claims are directed to a composition comprising a polyamine, such as spermidine, and methods of increasing oxidative phosphorylation and treating cancer comprising administering the composition and a PD-1 signaling inhibitor.
Regarding the composition of claim 1 and 15, Kromer teaches a composition comprising at least one caloric restriction mimetic [0123], including spermidine (abstract). Since Kroemer teaches all the required components of the pharmaceutical composition, Kroemer teaches the pharmaceutical composition. The limitation of claim 1 directed to increasing the function of oxidative phosphorylation in T cells is an inherent property of spermidine, and thus Kromer teaches all limitations of the claim. See MPEP 2112.I and 2112.II: "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003).
Kromer teaches methods comprising administering caloric restriction mimetics and an immunotherapy targeting the immune checkpoint molecule PD-1 for the treatment of cancer (abstract); the caloric restriction mimetic can be spermidine [0008], which reads on the methods of instant claims 4, 6, 12, 15, and 17-18. Because the only active step recited in claim 4 is administration and because Kromer teaches this step, the reference inherently teaches the method of increasing oxidative phosphorylation, as required by instant claims 4 and 9.
The PD-1 inhibitor of Kromer may be an anti-PD-L1 antibody ([0004], [00850]), which reads on claims 7 and 23. The composition of Kromer is simultaneously administered with at least at least one immune-checkpoint inhibitor [0123], which reads on instant claims 4, 12, and 19.
Kromer teaches that the antibody can be administered at a dose about 0.02-100 mg/kg and the caloric restriction mimetic can be administered at 0.1-100 mg/kg [0158], with a calculated antibody to drug ratio of 1:1 to 1:0.2, which overlaps with the mass ratio of the PD-1 signaling inhibitor to polyamine pharmaceutical composition of 1:2 to 1:0.1 of instant claim 16.
All claims are anticipated by Kromer.
Conclusion
No claim is allowed.
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 JENNIFER BENAVIDES whose telephone number is (571)272-0545. The examiner can normally be reached M-F 9AM-5PM (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at (571)272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675