DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2 Applicant's amendment, filed on 04/23/2026, is acknowledged.
3. Claims 1, 3-11, 13-18, 23, 27 are pending.
4. Applicant’s election of Group I, claims 1, 3-8, 13, 16-18 directed to anti-PD-1 antibody and the species of 1G1-h70, e.g., SEQ ID NOs: 1, 3, 5, 60, 9, 11, 58, and 59 for (a), elect "humanized antibody", "multispecific antigen binding molecule" and elect non-small cell lung cancer, lupus, Alzheimer's disease or hepatitis B, filed on 04/23/2026, is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
5. Claims 9-11, 14-15, and 27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions.
6. Claims 1, 3-8, 13, 16-18 are under examination as they read on anti-PD-1 antibody and the species of 1G1-h70, e.g., SEQ ID NOs: 1, 3, 5, 60, 9, 11, 58, and 59 for (a), elect the species "humanized antibody", "multispecific antigen binding molecule" and elect non-small cell lung cancer, lupus, Alzheimer's disease or hepatitis B.
7. Applicant’s IDS, filed 08/01/2023, 09/28/2023, 01/02/2024, 06/13/2025 and 04/22/2026, is acknowledged.
8. The following is a quotation of 35 U.S.C. 112(b) (Pre AIA , 35 U.S.C. 112, second paragraph):
(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.
9. Claims 13 are rejected under 35 U.S.C. 112(b), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
(i) the recitation “a camelized single domain
10. The following is a quotation of 35 U.S.C. 112(a) (Pre-AIA 35 U.S.C. 112, first paragraph):
(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.
10. Claims 1, 3-4, 13, 16-18 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.
Claims 1, 3-4 encompass a broad genus of anti-PD-1 antibody that binds to a conformational epitope comprising amino acids P130, L128, N66, Y68, K78, A129, and A132 of SEQ ID NO: 62 having an equivalent level of binding affinity for human/mouse PD-1 with a KD of 9E-10M or less at pH6.0.
Qy 1 MQIPQAPWPVVWAVLQLGWRPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MQIPQAPWPVVWAVLQLGWRPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTS 60
Qy 61 ESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGT 120
Qy 121 YLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLVVGVVGGLLGS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 YLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLVVGVVGGLLGS 180
Qy 181 LVLLVWVLAVICSRAARGTIGARRTGQPLKEDPSAVPVFSVDYGELDFQWREKTPEPPVP 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 LVLLVWVLAVICSRAARGTIGARRTGQPLKEDPSAVPVFSVDYGELDFQWREKTPEPPVP 240
Qy 241 CVPEQTEYATIVFPSGMGTSSPARRGSADGPRSAQPLRPEDGHCSWPL 288
||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 CVPEQTEYATIVFPSGMGTSSPARRGSADGPRSAQPLRPEDGHCSWPL 288
However, there does not appear to be an adequate written description in the specification as-filed of the essential structural feature that provides the recited function of binding to PD-1. The Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement make clear that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus.
[0276] The relative change in tumor size and tumor growth inhibition rate over time for each group are shown in FIG. 17. The 1G1-h70 antibody showed significantly superior tumor growth inhibition compared to the mouse PD-1 antibody, RMP1-14. It is known that the MC38 colorectal cancer syngeneic model does not respond well to anti-PD-1 therapy. Therefore, the excellent tumor growth inhibitory effect of the 1G1-h70 antibody was unexpected. Meanwhile, there was no statistically significant change in the body weight of mice due to treatment in each group (data not shown).
[0227] To confirm the binding between the monoclonal cell (hybridoma) (1G1) prepared in Example 3 and the conformational PD-1 protein expressed on the cell surface, cell-based ELISA and flow cytometry analysis were performed. As an anti-hPD-1 antibody control, Keytruda (Invivogen) was used.
[0278] Analysis of the interaction between 1G1-h70 Fab and PD-1 showed that 1G1-h70 antibody formed hydrogen bonds with residues N66, Y68, K78, A129, P130, and A132 on the PD-1 antigen (SEQ ID NO: 62). Of these, Y68, K78, and N66 have side chains involved in hydrogen bonding.
[0279] Also, the interaction analysis between 1G1-h70 Fab and PD-1 showed that 1G1-h70 antibody formed hydrophobic bonds with residues I126, L128, A129, P130, and A132 on the PD-1 antigen (SEQ ID NO: 62). As also confirmed through the Ala scanning experiment of Example 11, the three amino acid residues (P130, L128, I126) found to play the most important role in binding to the 1G1 antibody are located in the FG loop region of PD-1, and it appears that the hydrophobic interactions formed by the residues exert synergy, contributing significantly to the binding affinity.
[0280] It is known that the loop regions in the PD-1 molecule are very flexible and adopt an appropriate conformation for binding depending on the binding partner.
As the anticancer efficacy of anticancer drugs including immune-oncology antibodies is affected by the low pH of the tumor microenvironment, the 1G1-h70 antibody's strong binding affinity to human PD-1 even at the low pH of the tumor microenvironment provides a basis for conferring excellent anticancer activity in the tumor microenvironment in vivo [0284].
[0285] Affinity maturation was performed to increase the affinity of the 1G1-h70 antibody for human PD-1. Each amino acid residue in the CDR region of the 1G1-h70 antibody was mutated into other 19 amino acids using optimal codons for E. coli. DNA oligonucleotide libraries were synthesized on microarrays, and clones were selected for expression in E. coli.
[0288] After affinity maturation, a total of 13 humanized PD-1 antibodies (AHF16556, AHF16557, AHF16558, AHF16559, AHF16560, AHF16561, AHF16563, AHF16564, AHF16565, AHF16566, AHF16568, AHF16569, and AHF16570) were obtained. These antibodies had amino acid substitutions in the three CDR regions (VH CDR2, VH CDR3, VL CDR1) compared to the 1G1-h70 parent antibody (WT) as shown in Table 5.
Claims 1, 3-4 encompass a broad genus of anti-PD-1 antibody that binds to a conformational epitope comprising amino acids P130, L128, N66, Y68, K78, A129, and A132 of SEQ ID NO: 62 having an equivalent level of binding affinity for human/mouse PD-1 with a KD of 9E-10M or less at pH6.0.
The claims are broadly drawn to any antibody which binds to a conformational epitope formed
by amino acids P130, L128, N66, Y68, K78, A129, and A132 of SEQ ID NO: 62. However, the specification does not provide adequate written description of a sufficient representative number of antibodies falling within the scope of the genus and has not described the antibody structural features common or shared among the antibodies having the claimed binding function sufficient to describe the entire genus of antibodies meeting the claims. Regarding the lack of structure/function description, a disclosure of one or two antibodies do not predict the entire claimed genus of any and all other anti- amino acids P130, L128, N66, Y68, K78, A129, and A132 of SEQ ID NO: 62 antibodies yet to be discovered that function as claimed.
The USPTO has released a Memo on the Clarification of Written Description Guidance For Claims Drawn to Antibodies and Status of 2008 Training Materials, 02/22/2018.
See https://www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf.
The Memo clarifies the applicability of USPTO guidance regarding the written description requirement of 35 U.S.C. § 112(a) concerning the written description requirement for claims drawn to antibodies, including the following.
“In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional”.
In contrast to applicant’s reliance of describe the epitope comprising amino acids P130, L128, N66, Y68, K78, A129, and A132 of SEQ ID NO: 62 in providing a fully characterized antigen / specific epitope as well as claiming structural elements of the antigen and binding affinity, there is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed anti-epitope P130, L128, N66, Y68, K78, A129, and A132 of SEQ ID NO: 62 antibodies to demonstrate possession.
Also, see Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017).
There is no evidence that knowledge of the chemical structure of an antigen gives the required kind of structure identifying information about the corresponding antibodies Applicants attempt to describe the invention by describing something that is not the invention: viz., the antigens to which the antibodies may bind. There nothing in the disclosure that describes the antibodies as required by the test set forth in Ariad.
However, the anti-PD-1 antibodies are required to practice the invention. The specification fails to provide any specific structural or physical information so as to define a genus of antibodies having the desired therapeutic properties. Applicant is merely relying on the identification of PD-1 as the antigen and the well-known structure of antibodies in general. However, the claims do not recite a general antibody, but an antibody having a specific desired activity. However, Federal Circuit clarification of the law of written description as it applies to antibodies. Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017).
The claims are directed to a genus of anti-PD-1 antibodies. However, Federal Circuit clarification of the law of written description as it applies to antibodies. The U.S. Court of Appeals for the Federal Circuit (Federal Circuit) decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), which concerned adequate written description for claims drawn to antibodies. The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called "newly characterized antigen" test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. § 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the "newly characterized antigen" test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional.
Moreover, there is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed anti-PD-1 antibodies to demonstrate possession. Also, see Amgen Inc. v. Sanofi, Aventisub LLC, No. 2017-1480 (Fed. Cir. 2017). The Court reiterated that adequate written description must “contain enough information about the actual makeup of the claimed products . . . .” The Court simultaneously suggested that the “newly characterized antigen” test “flouts” section 112 because it “allows patentees to claim antibodies by describing something that is not the invention, i.e. the antigen.” The Court concluded that for written description of an antibody to be adequate when presented with “functional” terminology, there must be an established correlation in the art between structure and function.
The claims recite the antigen, and not the much larger functional genus of claimed antibody. See
Amgen, 872 F.3d at 1378. “Functionally defined claims can meet the written description
requirement if a reasonable structure-function correlation is established, whether by the inventor
as described in the specification or known in the art at the time of the filing date.” Id. The record
here does not indicate an established structure-function correlation between the claimed antibody
and the binding function. The instant disclosure is insufficient to satisfy the written description
requirement.
For instance, citing to Centocor, the Court analogized an antigen and antibody to a lock and a key. For an antigen where there is only a finite number of binding antibodies, discovering those antibodies may be routine and conventional, and description of the antigen alone may be sufficient. By contrast, for antigens with millions of keys, or millions of potentially binding antibodies, description of the antigen and even a couple of examples may be far from sufficient.
Artisans are well aware that knowledge of a given antigen (for instance PD-1) provides no information concerning the sequence/structure of antibodies that bind the given antigen. For example, Edwards et al (J Mol Biol. 2003 Nov 14;334(1): 103-18) teach that over 1,000 different antibodies to a single protein can be generated, all with different sequences spanning almost the entire heavy and light chain germline repertoire (42/49 functional heavy chain germlines and 33 of 70 V-lambda and V-kappa light chain germlines, and with extensive diversity in the FICDR3 region sequences (that are generated by VDJ germline segment recombination) as well, see entire document). Similarly, Lloyd et al (Protein Eng Des Sel. 2009 Mar;22(3):159-68) teach that a large majority of VH/VL germline gene segments are used in the antibody response to an antigen, even when the antibodies were selected by antigen binding, as their sequencing studies revealed that out of 841 unselected and 5,044 selected antibodies, all but one of the 49 functional VH gene segments was observed (see entire document). Goel et al (J Immunol. 2004 Dec 15; 173(12):7358-67) disclose the synthesis of three mAbs that bind to the same short (12-mer) peptide and found that the sequences of these antibodies which bound the same epitope exhibited diverse V gene usage indicating their independent germline origin (see entire document). As such, it does not seem possible to predict the sequence/structure of an antibody that binds a given antigen as there does not appear to be any common or core structure present within all antibodies that gives rise to the function of antigen binding. Further, given data such as that of Edwards et al. indicating the diversity of sequence bound in a population of antibodies that bind to a given antigen no number of species appears to reasonably representative of the breadth of the genus of antibodies that bind the given antigen. Indeed, Kanyavuz et al (Nat Rev Immunol. 2019 Jun; 19(6):355-368) teach that “Theoretically, under physiological conditions, the human immune system can generate BCRs with 1026 distinct sequences, an astronomical number that is far greater than the calculated number of all B cell clones that can be generated during the lifespan of a healthy human (estimated to be 4 x 1014).
While the amino acid sequence of PD-1 of SEQ ID NO: 62 was known, immunizing an animal with PD-1 will generate antibodies directed to a number of different epitopes within the non-contiguous conformational epitope of SEQ ID NO: 62 and not necessarily to the same epitope P130, L128, N66, Y68, K78, A129, and A132 of SEQ ID NO: 62 recited in claims. The knowledge of the amino acid sequence of PD-1, by itself, did not put Applicants in possession of a genus of antibodies that bind epitope P130, L128, N66, Y68, K78, A129, and A132 of SEQ ID NO: 62.
Possession is 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,
358 F.3d at 927, 69 USPQ2d at 1895. Sufficient description to show possession of such a genus
may be achieved by means of a recitation of anti-Galectin competing antibodies falling within the scope of the genus or of a recitation of structural features common to members of the genus,
which features constitute a substantial portion of the genus. See Eli Lilly, 119F.3d at 1568, 43
USPQ2d at 1406.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear 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.). Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 USPQ2d 1398.
Applicant is invited to point to clear support or specific examples of the claimed invention in the specification as-filed.
11. Claim 18 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as containing subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The intended use recited in claim 18 is at issue. The instant claims are drawn to a large genus of intended methods which have not been developed yet to the point where a specific benefit exists in currently available form.
Besides the melanoma and colorectal cancer treatment, the specification disclosure does not enable one skilled in the art to practice the invention without an undue amount of experimentation.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
The instant specification fails to provide any animal model for treating any condition associated with PD-1 disease including non-small cell lung cancer, lupus, Alzheimer's disease or hepatitis B
FIG. 15 shows tumor growth over time and tumor growth inhibition according to dose of the 1G1-parental antibody (see example 15 and [0274]). The 1G1-h70 antibody showed significantly superior tumor growth inhibition compared to the mouse PD-1 antibody, RMP1-14 [0276] .
Regarding in vivo methods which rely on generally unpredictable mechanisms, ''The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.'' In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction'' refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling (MPEP 2164.03).'' The MPEP also states that physiological activity can be considered inherently unpredictable.
Further, in Rasmusson v. SmithKline Beecham Corp., 75 USPQ2d 1297-1303 (CAFC 2005), the court states “If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to “inventions” consisting of little more than respectable guesses as to the likelihood of their success. When one of the guesses later proved true, the 'inventor' would be rewarded the spoils instead of the party who demonstrated that the method actually worked. That scenario is not consistent with the statutory requirement that the inventor enable an invention rather than merely proposing an unproved hypothesis.”
The MPEP states that the issue of "correlation" is also dependent on the state of the prior art. In other words, if the art is such that a particular model is recognized as correlating to a specific condition, then it should be accepted as correlating unless the examiner has evidence that the model does not correlate. Even with such evidence, the examiner must weigh the evidence for and against correlation and decide whether one skilled in the art would accept the model as reasonably correlating to the condition. See MPEP 2164.02.
The standard for determining whether the specification meets the enablement requirement was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 U.S. 261, 270 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? That standard is still the one to be applied. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The burden of enabling the prevention of a disease (i.e. the need for additional testing) would be greater than that of enabling a treatment due to the need to screen those mammals susceptible to such diseases and the difficulty of proof that the administration of the drug was the agent that acted to prevent the condition. Further, the specification does not provide guidance as to how one skilled in the art would go about screening those patients susceptible to conditions associated with PD-1 including non-small cell lung cancer, lupus, Alzheimer's disease or hepatitis B within the scope of the presently claimed invention. Nor is sufficient guidance provided as to a specific protocol to be utilized in order to prove the efficacy of the presently claimed anti-PD-1 antibody in preventing conditions associated with PD-1 including non-small cell lung cancer, lupus, Alzheimer's disease or hepatitis B state.
In view of the lack of predictability of the art to which the invention pertains the lack of established clinical protocols for effective PD-1 based therapies for the claimed conditions, undue experimentation would be required to practice the intended methods with a reasonable expectation of success, absent a specific and detailed description in applicant’s specification of how to effectively practice the intended methods and absent working examples providing evidence which is reasonably predictive that the claimed methods are effective for reducing chemokine-mediated migration of leukocytes in an inflammatory disease or disorder.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
12. 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.
13. Claims 1, 4, 13, 16-18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 20190144542 A1.
The `542 publication teaches anti-PD-1 antibodies that bind to an epitope of PD-1 that includes residues V64, L128, P130, K131, and A132 of SEQ ID NO: 1 (such as a 12819 antibody, e.g., antibody 12819.15384) [0296]. The `542 publication teaches that human PD-L1 binds human PD-1 through contact residues V64, N66, Y68 situated in the C p-strand and G124, I126, L128, A132, 1134 and E136 located in the F and G p-strands [0440]. The `542 publication also claims anti-PD-1 antibody that binds to an epitope on the PD-1 comprising amino acid residues 69-90 and 122-140 of SEQ ID NO: 1 or amino acid residues 56-64, 69-90, and 122-140 of SEQ ID NO: 1 (see published claim 1). Table 13 of the `542 publication show that anti-PD-1 antibody binds N66, K78, L128 (see Table 13). The `542 publication teaches that the antibody includes antibody portions, such as Fab and F(ab′)2 fragments[0108].
[0350] Formulations of a pharmaceutical composition suitable for parenteral administration typically comprise the active ingredient combined with a pharmaceutically acceptable carrier,
Given the high sequence identity/homology between the referenced/claimed epitopes; the referenced antibodies would have the inherent property of binding PD-1 at the claimed positions because antibody crossreacts with another antibody based on commonly shared amino acids in the epitope.
Claim 4 is included because the `542 publication teaches antibody is said to specifically bind to an antigen when the KD is ≤1 mM, preferably ≤100 nM [0096]. [0424] This example demonstrates that the majority of anti-PD-1 antibodies show high picomolar (pM) affinity and good cross reactivity against both human and cynomolgus PD-1 extracellular domains (ECDs). The highest affinity antibody [12819.15384] binds human PD-1 with a KD of 20 pM [0426].
Claim 16 is included because the reference teaches a bispecific binding molecule having the binding specificity of an anti-PD-1 antibody [0076].
The reference teachings anticipate the claimed invention.
14. 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.
15. Claims 1, 3-8, 13, 16-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of copending Application No. 19/015698 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the `698 application are directed to a fusion protein comprising anti-PD-1 antibody 1G1 and humanized version 1G1-h70 comprising the claimed CDRs .
Alignment of claimed SEQ ID NO: 13 with SEQ ID NO: 38 of `698 application.
Qy 1 EVQLQQSGAELVKPGASVKLSCKASGYTFTGYWMHWVKQRPGQGLEWIGMIHPNSDTTTY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLQQSGAELVKPGASVKLSCKASGYTFTGYWMHWVKQRPGQGLEWIGMIHPNSDTTTY 60
Qy 61 NEKFKNRATLTVDKSSGTAYMQLSSLTSEDSAVYYCTGTDQAAWFAFWGQGTLVTVSA 118
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NEKFKNRATLTVDKSSGTAYMQLSSLTSEDSAVYYCTGTDQAAWFAFWGQGTLVTVSA 118
Alignment of claimed SEQ ID NO: 15 with SEQ ID NO: 39 of `698 application.
Qy 1 DIVLTQTPLSLPVSLGDQASISCRSSQNIVHSNGDTYLEWYLQKPGQSPKLLIYKVSKRF 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIVLTQTPLSLPVSLGDQASISCRSSQNIVHSNGDTYLEWYLQKPGQSPKLLIYKVSKRF 60
Qy 61 SGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPWTFGGGTKLEIK 112
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPWTFGGGTKLEIK 112
Alignment of claimed SEQ ID NO: 58 with SEQ ID NO: 44 of `698 application.
Qy 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYWMHWVRQAPGQGLEWIGMIHPNSDTTTY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYWMHWVRQAPGQGLEWIGMIHPNSDTTTY 60
Qy 61 NEKFKNRVTMTRDTSISTAYMELSRLRSDDTAVYYCAGTDQAAWFAFWGQGTTVTVSS 118
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NEKFKNRVTMTRDTSISTAYMELSRLRSDDTAVYYCAGTDQAAWFAFWGQGTTVTVSS 118
Alignment of claimed SEQ ID NO: 59 with SEQ ID NO: 45 of `698 application.
Qy 1 DIVMTQTPLSLSVTPGQPASISCRSSQNIVHSQGDTYLEWYLQKPGQSPQLLIYKVSKRF 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIVMTQTPLSLSVTPGQPASISCRSSQNIVHSQGDTYLEWYLQKPGQSPQLLIYKVSKRF 60
Qy 61 SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPWTFGGGTKVEIK 112
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPWTFGGGTKVEIK 112
The claims of the `698 application anticipate the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
16. No claim is allowed.
17. The art made of record and not relied upon is considered pertinent to applicant's disclosure:
18. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM to 4:30PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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June 4, 2026
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644
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