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 .
Election/Restrictions
Applicant's election with traverse of group I, claims 1-3, 8, 10-12, 14-15, 17, 20, 22, 25, 27, 30-31, 39, 41, 43, 45, 128-129, 132, 135, 138-139, 142-144, 146-148, 151, 153, 156, 158, 161, 163, and 166, and species (1) antibody of SEQ ID NOs: 3 and 5 for the agent that blocks PD-L2; (2) antibody of SEQ ID NOs: 17 and 16 for agent that blocks RGMb; (3) cemiplimab as the agent that blocks PD-1; (4) atezolizumab as the agent that blocks PD-L1, and (5) colon cancer as the cancer in the reply filed on January 12, 2026 is acknowledged. The traversal is on the ground(s) that Groups I and II are related as a process of use of a product and a product and that Groups I and II share a special technical feature. Applicant contends that the common structures represent a significant structural element shared by all of the alternatives. This is not found persuasive because, as set forth in the Restriction Requirement mailed on November 10, 2025, the shared technical feature between Groups I and II is not a special technical feature in view of Umezu et al, published online October 24, 2018 (see PTO-892 from 11/10/2025), which teaches simultaneous administration of anti-PDL1 antibody and anti-PDL2 therapy to mice (Figure 3). The requirement is still deemed proper and is therefore made FINAL.
Claims 12, 48, 50-51, 53, 55-56, 58, 60-63, 65, 68-70, 73-75, 78-80, 83-84, 86, 139, and 148 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on December 12, 2025.
Claims 1-3, 7-8, 10-11, 14-15, 17, 20, 22, 25, 27, 30-31, 39, 41, 43, 45, 128-129, 132, 135, 138, 142-144, 146-147, 151, 153, 156, 158, 161-163, and 166 are under consideration in this office action.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The application is the national stage entry of PCT/US21/50674, which claims benefit to U.S. Provisional Application No. 63/079,245, filed September 16, 2020.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on May 11, 2023, February 12, 2025, and September 23, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDSs are being considered by the examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification (pg 2, 4, 6, 10) and claims 7 and 143 are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Objections to Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (pg 39). 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.
The specification also appears to identify incorrectly the two anti-PD-L2 antibodies on pages 2, 4, 6, and 9 of the disclosure. According to the specification (pg 68), the antibody 1B9 is comprised of heavy chain variable region of SEQ ID NO: 3 and light chain variable region of SEQ ID NO: 6, and the antibody 4H1 is comprised of heavy chain variable region of SEQ ID NO: 5 and light chain variable region of SEQ ID NO: 4. The elected species of anti-PD-L2 antibody of heavy chain variable domain of SEQ ID NO: 3 and light chain variable domain of SEQ ID NO: 5 is actually comprised of nucleic acid sequences encoding two heavy chain variable domains. If this is an error by applicant, an updated specification should be provided with the correct anti-PD-L2 structures.
Claim objections
Claims 3 is objected to because of the following informalities:
Claim 3 improperly recites, “the first agent is an is an antibody”. Removing the additional “is an” would be sufficient to overcome this objection.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-3, 7-8, 10-11, 14-15, 17, 20, 22, 25, 27, 30-31, 41, 43, 45, 132, 135, 144, 153, and 161 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.
Claim 1 identifies the patient who will be administered the combination therapy as one “that has failed an anti-PD1/PD-L1 therapy”. The use of a forward slash to separate PD1 and PD-L1 renders the claim indefinite because it is unclear if the failed therapy is a monotherapy comprising either anti-PD1 antibody therapy or anti-PD-L1 therapy or if the failed therapy is a combination therapy comprising both anti-PD1 and anti-PD-L1 antibodies. This rejection may be overcome by using the conjunction “or” instead of the forward slash.
There is a possible error in the claimed sequences for the heavy chain variable domain and light chain variable domain of the anti-PD-L2 antibodies of claims 8 and 144. According to the specification (pg 68), the antibody 1B9 is comprised of heavy chain variable region of SEQ ID NO: 3 and light chain variable region of SEQ ID NO: 6, and the antibody 4H1 is comprised of heavy chain variable region of SEQ ID NO: 5 and light chain variable region of SEQ ID NO: 4. The elected species of anti-PD-L2 antibody of heavy chain variable domain of SEQ ID NO: 3 and light chain variable domain of SEQ ID NO: 5 is actually comprised of nucleic acid sequences encoding two heavy chain variable domains. Therefore, the structure of the claimed antibody is unclear. In the interest of compact prosecution, the elected antibody is interpreted to be comprised of heavy chain variable region SEQ ID NO: 3 and light chain variable region of SEQ ID NO: 6.
The term “related” in claims 11 and 147 is a relative term, which renders the claim indefinite. The phrase “structurally related” to antibodies 24F.10C12, GF17.2C9, MIH37, 3.2, or TY25 is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Apart from being antibodies, in what ways are the claimed antibodies similar in structure to the recited antibodies of the claims? Since the scope of the claimed antibodies is unclear; one of ordinary skill in the art and or competitors would be unable to discern the bounds of the claimed invention. In the interest of compact prosecution, the antibody that blocks PD-L2 that is structurally related to 24F.10C12, GF17.2C9, MIH37, 3.2, or TY25 is interpreted to be an anti-PD-L2 antibody.
Claim 11 is rejected as vague and indefinite for reciting the term “3.2” as the sole means of identifying the antibody. If 3.2 is a laboratory designation, using such a designation as the only means to identify the particular antibody renders the claims indefinite because different laboratories may use the same laboratory designations to define completely distinct molecules. It is also well known in the art that molecule names can be altered, deleted, amended, or revised over time by inventors and authors. Hence, one of ordinary skill in the art and or competitors would be unable to discern the bounds of the claimed invention. The rejection can be obviated, for example, by amending the claim to specifically and uniquely identify the antibody by heavy and light chain variable region amino acid sequences.
Claims 25 and 161 use parentheses to enclose REGN2810, BMS-836558, MDX-1106, ONO-4538, MK-3475, SCH 900475, IBI308, PDR001, BGB-A317, and JS001. Claims 30 and 166 use parentheses to enclose MPDL3280A, RG7446, RO5541267, MEDI4736, MEDI-4736, and MSB0010718C. The use of parentheses that encompass a limitation in the claim is found indefinite because it is unclear whether the limitations within the parentheses are part of the claimed invention or are just set forth as possible examples.
Claims 8, 17, 144, and 153 recite the limitations "the heavy chain variable domain” and “the light chain variable domain". There is insufficient antecedent basis for these limitations in the claims.
Claim 132 recites the limitation “the patient”. There is insufficient antecedent basis for this limitation in the claim.
Regarding claims 31 and 43, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 2-3, 7, 10, 14-15, 20, 22, 27, 30, 41, 45, and 135 are included in this rejection for being dependent on a rejected base claim and failing to cure the indefiniteness.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 132 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 132 is limited to a patient that has been treated with anti-PD1 therapy, anti-PD-L1 therapy, or both the anti-PD1 therapy and the anti-PD-L1 therapy. Claim 132 is dependent from claim 128, which is limited to an individual that has failed a therapy of anti-PD1 therapy or anti-PD-L1 therapy, but not both therapies. The limitation of claim 132 is broadens the scope of the claim. Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
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 1-3, 7-8, 10-11, 14-15, 17, 20, 22, 25, 27, 30-31, 39, 41, 43, 45, 128-129, 132, 138, 138, 142-144, 146-147, 151, 153, 156, 158, 161-163, and 166 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 claims contain 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.
“[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.
Claim 10 recites an antibody/antigen-binding fragment thereof that is “fully human”. There is no support for this phraseology in the specification as originally filed. The disclosure fails to describe clearly these antibodies of claim 10 or show that the inventor was in possession of the human antibodies at time the invention was filed. Therefore, the limitation of claim 10 directed to a human antibody must be canceled from the claim.
All claims under consideration are drawn to a method of treating cancer in an individual that has failed an anti-PD1/PD-L1 therapy, wherein the individual is administered a first agent that blocks or disrupts PD-L1, RGMb, or both and a second agent that blocks or disrupts PD-L1, PD-1, or both. The claims are drawn to broad genera of PD-1, PD-L1, PD-L2, and RGMb blockers. For any given claim, at least one of these agents is left only defined by function, i.e. what it blocks. In the dependent claims, the blockers of PD-1, PD-L1, PD-L2, and RGMb are further limited to antibodies, and, thus, the discussion below will focus on why the genera of antibodies, as claimed, does not meet the written description requirement.
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).
There is no way to a priori look at an antigen sequence (e.g., PD-1) 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 (instant PTO-892), 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.
According to the specification, the applicant has disclosed a number of antibody species for PD1, PD-L1, PD-L2, and RGMb, which are known in the art and are comprised of specific combinations of heavy chain CDRs and light chain CDRs. However, the specification does not provide adequate written description for the entire claimed genera of antibodies, 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 which heavy chain and light chain amino acid sequences should be combined to yield an antigen-binding region that is capable of binding, for example PD-1.
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 genera of anti-PD-1, PD-L1, PD-L2, and RGMb antibodies encompassed by the instant claims, especially in view of the unpredictability of such an endeavor. The prior art, as evidenced by Edwards et al., 2003 (instant PTO-892), 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”).
Applicant has not described the claimed invention sufficiently to show they had possession of the claimed genera of antibodies that bind PD1, PD-L1, PD-L2, and RGMb. Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester v. G.D. Searle & Co., 358 F.3d 916, 69 USPQ2d 1886 (Fed. Cir. 2004).
To provide adequate written description and evidence of possession of the claimed genera, the specification must provide sufficient distinguishing identifying characteristics of each 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 one generic, broad genus that encompassed 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 genera of antibodies.
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 20 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, for example PD1, 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 with specific CDRs, 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, 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 reference to a potential method of isolating it. The product itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
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, all claims do not meet the written description requirement.
Claim Rejections - 35 USC § 102
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.
Claims 1-3, 10-11, 14-15, 20, 22, 27, 31, 39, 41, 43, 45, 128-129, 132, 135, 138, 142, 146-147, 151, 156, 158, and 162-163 are rejected under 35 U.S.C. 102(a)(1) and 102 (a)(2) as being anticipated by US 2018/0002422, published January 4, 2018 (“Freeman”; instant PTO-892)
Freeman teaches a method of treating a subject with cancer who is responsive to PD-1 blockade alone comprising administering a combination of agents that selectively blocks RGMb and PD-1 [0007]. According to the specification (pg 19):
“an individual is considered to have failed an anti-PD-1/PD-L1 therapy if the treated cancer is resistant to therapy, if the treated cancer has no response or an incomplete response (e.g., a response that is less than a complete remission) to the therapy, if the treated cancer progresses or relapses after the therapy, if the individual that initially responds to therapy but develops a resistance to the therapy, or if the individual has been taken off of the therapy due to intolerance to the therapy”
Freeman teaches that combination therapy comprising anti-PD1 antibody and anti-RGMb antibody for cancer, “especially where PD-1 blockade has some efficacy and/or may be insufficient” [0017]. Also, the methods of Freeman can be applied “for enhancing the efficacy of a cancer therapy… for sensitizing hyperproliferative or otherwise cancerous cells (e.g., resistant cells) to the cancer therapy” [0062]. As the combination therapy of Freeman is administered to those who are not completely responsive to PD-1 monotherapy, Freeman reads on the methods of claims 1, 39, 128-129, 132, and 135 directed to a patient who has previously received and failed a PD-1 therapy and is administered as a combination therapy of PD-1 blocker and RGMb blocker. The pharmaceutical composition comprising the agents that block RGMb and PD-1 of Freeman can be delivered intravenously [0220], which reads on instant claim 31.
The RGMb blocker of Freeman may be an anti-RGMb antibody [0006], which reads on claims 2, 14, and 138; further, the anti-RGMb antibody may be humanized [0006], which reads on claims 15 and 151. The PD-1 or PD-L1 blocker is an anti-PD-1 antibody [0006], which reads on instant claims 20, 156, and 162; the anti-PD-1 antibody may be a humanized antibody [0006], which reads on instant claims 22, 158, and 163.
Freeman teaches that the method of treating cancer comprising administering a combination of agents that selectively blocks RGMb and PD-1 may also comprise an anti-PD-L2 antibody or an anti-PD-L2 antibody [0247], which reads on instant claims 3, 11, 27, 142, and 147. The antibodies of Freeman may be monoclonal [0025] or bispecific antibodies [0024], which reads on claims 10, 27, 142, and 146.
Freeman teaches that the cancer is a colorectal cancer ([0004],[0007],[0029]), which reads on claims 41, 43, and 45.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-3, 7-8, 10-11, 14-15, 20, 22, 27, 31, 39, 41, 43, 45, 128-129, 132, 135, 138, 142-144, 146-147, 151, 156, 158, and 162-163 are rejected under 35 U.S.C. 103 as being unpatentable over US 2018/0002422, published January 4, 2018 (“Freeman”) in view of US 2018/0201680, published July 19, 2018 (“Sharpe”; instant PTO-892).
Freeman teaches a method of treating a subject with cancer who is responsive to PD-1 blockade alone comprising administering a combination of agents that selectively blocks RGMb and PD-1 [0007]. Freeman does not teach the anti-PD-L2 antibodies of claims 7-8 and 143-144.
Sharpe teaches antibodies that bind the immunogenic epitope CFTVTVPKDLYVVEYGSN [0120], as in the anti-PD-L2 antibodies of instant claims 7 and 143.
Sharpe teaches antibodies comprised of heavy chain variable domain of SEQ ID NO: 15, which is identical to instant SEQ ID NO: 3, and light chain variable domain of SEQ ID NO: 17, which is identical to instant SEQ ID NO: 6, as in the anti-PD-L2 antibody of instant claims 8 and 144.
Given that Freeman teaches a method of treating a subject with cancer who is not responsive to PD-1 blocker therapy comprised of administering an anti-PD-1 antibody and an anti-PD-L2 antibody, and further given that Sharpe teaches the claimed anti-PD-L2 antibodies, it would have been obvious to one of ordinary skill in the art to substitute the antibodies taught by Sharpe in the method of Freeman. One of ordinary skill in the art would have been able to carry out such a substitution and the results would have been reasonably predictable. As is stated in MPEP §2144.06, substituting one equivalent element for another known for the same purpose renders an invention obvious and an “express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982)." One of ordinary skill in the art would have had a reasonable and predictable expectation of arriving at the claimed method based on the combined teachings of Freeman in view of Lee et al because substituting one known element for another to yield predictable results does not meet the threshold for a prima facie case of nonobviousness, absent convincing evidence to the contrary.
Claims 1-3, 10-11, 14-15, 17, 20, 22, 27, 31, 39, 41, 43, 45, 128-129, 132, 135, 138, 142, 146-147, 151, 153, 156, 158, and 162-163 are rejected under 35 U.S.C. 103 as being unpatentable over US 2018/0002422, published January 4, 2018 (“Freeman”) in view of US 2016/0347844, published December 1, 2026 (“Dekruyff”; instant PTO-892).
Freeman teaches a method of treating a subject with cancer who is responsive to PD-1 blockade alone comprising administering a combination of agents that selectively blocks RGMb and PD-1 [0007]. Freeman does not teach the anti-RGMb antibody of claims 17 and 153.
Dekruyff teaches the anti-RGMb antibody comprised of heavy chain variable domain encoded by SEQ ID NO: 28 and light chain variable domain encoded by SEQ ID NO: 26, which are identical to instant SEQ ID NOs: 17 and 16, respectively, as in claims 17 and 153.
Given that Freeman teaches a method of treating a subject with cancer who is not responsive to PD-1 blocker therapy comprised of administering a anti-PD-1 antibody and an anti-RGMb antibody, and further given that Dekruyff teaches the claimed anti-RGMb antibody, it would have been obvious to one of ordinary skill in the art to substitute the antibody taught by Dekruyff in the method of Freeman. One of ordinary skill in the art would have been able to carry out such a substitution and the results would have been reasonably predictable. As is stated in MPEP §2144.06, substituting one equivalent element for another known for the same purpose renders an invention obvious and an “express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982)." One of ordinary skill in the art would have had a reasonable and predictable expectation of arriving at the claimed method based on the combined teachings of Freeman in view of Lee et al because substituting one known element for another to yield predictable results does not meet the threshold for a prima facie case of nonobviousness, absent convincing evidence to the contrary.
Claims 1-3, 10-11, 14-15, 20, 22, 25, 27, 30-31, 39, 41, 43, 45, 128-129, 132, 135, 138, 142, 146-147, 151, 156, 158, 161-163, and 166 are rejected under 35 U.S.C. 103 as being unpatentable over US 2018/0002422, published January 4, 2018 (“Freeman”) in view of Lee et al, March 26, 2019 (instant PTO-892).
Freeman teaches a method of treating a subject with cancer who is responsive to PD-1 blockade alone comprising administering a combination of agents that selectively blocks RGMb, PD-1, and PD-L2 ([0007],[0247]). Freeman does not teach the anti-PD-1 antibody cemiplimab, as required by claims 25 and 161, or the anti-PD-L1 antibody atezolizumab, as required by claims 30 and 166.
Lee et al teaches that cemiplimab is an anti-PD-1 antibody (see Table 1, pg 3), as in claims 25 and 161, and that atezolizumab is an anti-PD-L1 antibody (see Table 1, pg 3), as in claims 30 and 166.
Given that Freeman teaches a method of treating a subject with cancer who is not responsive to PD-1 blocker therapy comprised of administering an anti-PD-1 antibody and an anti-PD-L2 antibody, and further given that Lee et al teaches the anti-PD-1 antibody cemiplimab and the anti-PD-L1 antibody atezolizumab, it would have been obvious to one of ordinary skill in the art to substitute the antibodies taught by Li et al in the method of Freeman. One of ordinary skill in the art would have been able to carry out such a substitution and the results would have been reasonably predictable. As is stated in MPEP §2144.06, substituting one equivalent element for another known for the same purpose renders an invention obvious and an “express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982)." One of ordinary skill in the art would have had a reasonable and predictable expectation of arriving at the claimed method based on the combined teachings of Freeman in view of Lee et al because substituting one known element for another to yield predictable results does not meet the threshold for a prima facie case of nonobviousness, absent convincing evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 7-8, 10-11, 14-15, 17, 20, 22, 25, 27, 30-31, 39, 41, 43, 45, 128-129, 132, 135, 138, 142-144, 146-147, 151, 153, 156, 158, 161-163, and 166 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,220,545 in view of US 2018/0002422, published January 4, 2018 (“Freeman”), US 2018/0201680, published July 19, 2018 (“Sharpe”), US 2016/0347844, published December 1, 2026 (“Dekruyff”), and Lee et al, March 26, 2019 (instant PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because they are directed to overlapping subject matter, a method of treating a subject with cancer comprising administering a combination of agents that selectively blocks RGMb and PD-1. Sharpe, Dekruyff, and Lee et al teach the elected antibodies.
The claims of ‘545 are directed to a method of treating a subject with cancer, wherein the patient is administered a combination of agents comprising a first antibody that binds to RGMb and a second antibody that binds to PD-1. ‘545 claims do not teach selection of a patient who has failed an anti-PD-1/PD-L1 therapy. Freeman teaches that combination therapy comprising anti-PD1 antibody and anti-RGMb antibody for cancer, “especially where PD-1 blockade has some efficacy and/or may be insufficient” [0017]. Also, the methods of Freeman can be applied “for enhancing the efficacy of a cancer therapy… for sensitizing hyperproliferative or otherwise cancerous cells (e.g., resistant cells) to the cancer therapy” [0062]. Thus, it would have been obvious to one of ordinary skill in the art to apply the method of ‘545 to the claimed patient population; one would do so with a reasonable expectation of success, given the findings that combination therapy is superior to PD-1 blocker monotherapy alone.
Dekruyff teaches the anti-RGMb antibody comprised of heavy chain variable domain encoded by SEQ ID NO: 28 and light chain variable domain encoded by SEQ ID NO: 26, which are identical to instant SEQ ID NOs: 17 and 16, respectively, as in claims 17 and 153.
Sharpe teaches antibodies that bind the immunogenic epitope CFTVTVPKDLYVVEYGSN [0120], as in the anti-PD-L2 antibodies of instant claims 7 and 143. Sharpe teaches antibodies comprised of heavy chain variable domain of SEQ ID NO: 15, which is identical to instant SEQ ID NO: 3, and light chain variable domain of SEQ ID NO: 17, which is identical to instant SEQ ID NO: 6, as in the anti-PD-L2 antibody of instant claims 8 and 144.
Lee et al teaches that cemiplimab is an anti-PD-1 antibody (see Table 1, pg 3), as in claims 25 and 161, and that atezolizumab is an anti-PD-L1 antibody (see Table 1, pg 3), as in claims 30 and 166.
Given that Freeman teaches a method of treating a subject with cancer who is not responsive to PD-1 blocker therapy comprised of administering an anti-PD-1 antibody and an anti-PD-L2 antibody or RGMb antibody, and further given that Sharpe teaches the claimed anti-PD-L2 antibodies, Dekruyff teaches the claimed anti-RGMb antibody, and Lee et al teach the anti-PD-1 antibody cemiplimab and the anti-PD-L1 antibody atezolizumab, it would have been obvious to one of ordinary skill in the art to substitute the antibodies taught by Sharpe, Dekruyff, and Li et al in the method of Freeman. One of ordinary skill in the art would have been able to carry out such a substitution and the results would have been reasonably predictable. As is stated in MPEP §2144.06, substituting one equivalent element for another known for the same purpose renders an invention obvious and an “express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982)." One of ordinary skill in the art would have had a reasonable and predictable expectation of arriving at the claimed method based on the combined teachings of Freeman in view of Lee et al because substituting one known element for another to yield predictable results does not meet the threshold for a prima facie case of nonobviousness, absent convincing evidence to the contrary.
The scope of the reference patent in view of Freeman, Sharpe, Dekruyff, and Lee et al full encompasses the scope of the instant claims, and the claims are not patentably distinct from each other.
Conclusion
No claim is allowed.
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Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675