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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
DETAILED ACTION
Election/Restrictions
This action is in response to claims filed 8/3/25. Claims 1-3, 6, 8, 10-11, 14-18, 20-22, 24, and 27-29 are pending.
Applicant’s election without traverse of Group I and the species of TrkB antibody, the VNAR defined by part (a) of claim 2, and VNAR-txp1 in the reply filed on 8/3/25 is acknowledged. It is also noted that Applicant has stated on the record that the elements of the Markush group in claim 6 are obvious variants (remarks 8/3/25 p. 2) and so the species election for that group is withdrawn.
In the interview on 6/30/25, it appears Applicant and the previous Examiner agreed to examination of Groups I and III. Upon further consideration, the restriction between groups I, II, III, IV, and V is withdrawn.
Regarding the species election, the interview summary on 6/30/25 states “the requirement for species election should be removed”. This appears to be in reference to the Markush group of claim 6, and the species requirement for that Markush group is withdrawn as noted above.
There is no comment on the species elections for D, E, and F as set forth in the Restriction requirement mailed 6/3/25. However, upon further consideration, these requirements are withdrawn.
Regarding the species election for B, while Applicant’s election is acknowledged, this requirement is also withdrawn, as these are fairly properties commensurate with the election of the particular VNAR and therapeutic.
Applicant’s election of the therapeutic as TrkB is acknowledged and remains in effect.
Applicant’s election of the VNAR as VNAR-txp1 is acknowledged and remains in effect. Note that the interview summary states that both parties agreed this species election was appropriate.
Examination of VNAR-txp1 has determined that this VNAR domain is allowable over the prior art (see allowable subject matter section below). Pursuant to MPEP §803, when the elected species is allowable, the Examiner extends examination to another species; the examiner extended the search to Clone C. As this species was deemed obvious (see §103 rejection below), the remaining non-elected species are still held as withdrawn (MPEP §803.02(III)).
Claim 21 is directed to TXB4, which is non-elected species (d) in claim 3. Claim 22 depends from claim 21 and defines conjugates which comprise TXB4; see, e.g., specification paragraph 137. Claim 10 is also directed to these TXB4 containing conjugates.
Therefore, claims 10, 21 and 22 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 8/3/25.
Claims 1-3, 6, 8, 11, 14-18, 20, 24, and 27-29 are under examination.
Priority
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
It is noted that the instant specification discloses subject matter which was not supported by priority document 62939522. For example, the instant specification references WO2019/089395 and WO2020/056327 at paragraph 16 for certain VNARs; these documents were not referenced in 62/939522 and so these disclosures are not supported in the priority document. The same is true of 63/112314, referenced in paragraph 16, which was filed after the priority document 62/939522 and so could not be supported by ‘522. Applicant is reminded that adding subject matter which was not supported by the priority documents will not afford the claimed priority.
Further, instant claim 3 recites “VNAR-txp1”. Priority document 62/939522 makes no mention of this VNAR either explicitly or implicitly. Therefore, claim 3 has an effective filing date of 11/20/2020, which is the PCT where this subject matter was newly added.
Claim Objections
Claims 15, 24, and 28 are objected to because of the following informalities:
- claim 15 states “a conjugate of claim 1 or claim 6”
- claim 24 states “a conjugate of claim 1”
- claim 28 states “a nucleic acid”
While the intention is clear, these phrases should use a definite article (e.g., “the”) to provide unequivocal antecedent basis as well as to be consistent with other uses of “the”, similar to “the vector” in claim 29 or “the conjugate” in claim 27.
Appropriate correction is required.
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 2 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.
The term “substantially” in claim 2 is a relative term which renders the claim indefinite. The term “substantially” 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.
Claim 2 requires a VNAR domain that binds TfR1 “without substantially interfering with transferrin binding”. Thus, the scope of “substantially” must be clear as it serves to warn others what infringes (a VNAR that does not substantially interfere) and what does not infringe (a VNAR that substantially interferes). However, there is no art recognized value for “substantially interfere” and is a subjective measure left to the particular user regarding how much interference one would deem “substantial”. Further, the specification provides no particular values nor definition of the term. The only example of “substantially” is in paragraph 81 regarding “substantially homologous”, where examples of “at least 45%” up to 99% are offered. This does not provide sufficient guidance to others to determine the metes and bounds of “substantially interfere” as this could be interference of 45%, 99%, or any other conceivable value as there is no clear indication in the specification as to the intended limits of this phrase as applied to interference.
Therefore, claim 2 is indefinite.
Claim 3 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 3 recites certain clones, e.g., Clone C, as well as “or one of its variants”.
In one interpretation, this is used in a similar manner as “or a variant thereof” and is meant to encompass any potential variant of Clone C. This is supported by an ordinary reading of the term as any variant—disclosed or otherwise—could fairly be considered “one of its variants”.
In another interpretation, this phrase is used to limit the claim to certain specific variants. For example, the specification at paragraph 52 refers to WO2018/031424 for a description of Clone C variants. This same paragraph also refers to nine named variants disclosed in WO2019/089395. As such, it is reasonable that the phrase is referring to specific variants rather than any variant, with the implication being “one of its [disclosed] variants”.
This second interpretation also creates indefiniteness as it is unclear which particular disclosed variants are meant to be encompassed by the phrase. While potentially all such variants are included, different sections of the specification call out different subsets of “variants” which may or may not be intended for the scope of the claim.
Therefore, claim 3 is indefinite. For the purpose of examination, the broadest reasonable interpretation is “any variant”. The examiner suggests that if this is correct, the phrase “or a variant thereof” would properly capture this aspect. If Applicant intends for the claim to be limited to specific variants, such variants should be explicitly named in the claim.
Claim 16 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 16 uses the term “preferably”. It is unclear if this is meant as a further limitation. In one case, “preferably” is being used to limit the claim to “intravenously”. However, if this is the case, it is unclear why the earlier Markush group is listed in the claim at all. In another interpretation, “preferably” is being used to offer a preference but not to limit the claim. However, a non-limiting preference does not belong in the claim as the claims are meant to set forth the limitations on the scope of what is being claimed; see MPEP § 2173.05(d) which states that “[d]escription of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim."
Therefore, claim 16 is indefinite.
Claims 17 and 18 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 17 states “said disease or condition” while claim 18 states “wherein said neurodegenerative disease or condition”; however, there is no previous recitation of a neurodegenerative condition. Claim 15 has two options: 1) a neurodegenerative disease and 2) a condition which responds to activation of neurotrophin receptor. Claim 17 only refers to “said disease or condition”. On its own, this phrase would reasonably refer to the neurodegenerative disease and the condition which responds to activation of neurotrophin receptor, though clarity would be improved by reciting the full phrases. Yet claim 18 is clearly directed to “said neurodegenerative disease or condition”, i.e., said neurodegenerative disease and said neurodegenerative condition. There is no earlier recitation of a neurodegenerative condition, but this also calls into question whether the “said condition” in claim 17 is this neurodegenerative condition or the condition which responds to activation of neurotrophin receptor.
Further, claim 18 states “an acute or chronic neurological injury or wound”. The multiple conjunctions make the phrase unclear. This could be:
An acute neurological injury
A chronic neurological injury
A wound
Alternately, “acute or chronic” may modify both “neurological injury” and “wound”, leading to:
1) An acute neurological injury
A chronic neurological injury
An acute wound
A chronic wound
Finally, it is unclear if “neurological” modifies just injury or both injury and wound, i.e., does the wound also need to be neurological?
Therefore, claims 17 and 18 are indefinite.
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 14 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 14 depends from claim 1. The only addition is the preamble “a pharmaceutical composition”. However, calling the composition “pharmaceutical” does not impart any specific structural requirement and there is no special definition of the phrase in the specification. When reading the preamble in the context of the entire claim, the recitation “pharmaceutical composition” is not limiting because the body of the claim describes a complete invention and the language recited solely in the preamble does not provide any distinct definition of any of the claimed invention’s limitations.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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, 6, 8, 11, 14-18, 20, 24, 27-29 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.
Claim 1 is directed to any BBB-shuttling VNAR domain. Claim 2 requires this domain specifically bind TfR-1 without substantially interfering with binding or transport. This VNAR is an antibody (e.g., instant specification paragraph 9-10) and as such, the claim is directed to an antibody defined entirely by function (binding). See MPEP §2163(I)(A) which states:
"The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.”
In this case, 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. The hyper variable regions (HVRs), i.e., complementarity determining regions (CDRs) of an antibody, are well established in the art as the portion of the binding region which imparts the specificity of an antibody. However, there is no way to a priori look at an antigen sequence (e.g., TfR) and envisage the combination of CDRs that will bind that antigen, such as in claim 2. Moreover, there is no way to envisage the structure of an antibody when provided solely with a desired function (e.g., BBB-shuttling) and no target at all, such as in claim 1. First, even highly related CDRs may not bind the same target. See for example Kussie (cited on form 892) who demonstrates that a single amino acid change in the heavy chain of an antibody which binds p-axophenylarsonate (Ars) completely abrogates the ability of the antibody to bind Ars but adds the functionality of binding the structurally related p-azophenylsulfonate (e.g., 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 (p.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 page 11). Specific to VNARs, Millan (form 892) teaches the effects of a single CDR3 mutation on the ability to bind an epitope may either increase or inhibit binding (abstract). Thus, the art recognizes that the CDRs define the binding properties of an antibody and that even single amino acid changes to this region can completely abrogate the binding specificity of an antibody. As a further example, see Chen (cited on form 892) which demonstrates single amino acid changes in the VH CDR2 sequence can increase binding, decrease binding, destroy binding, or have no effect on binding when compared to the wild-type antibody.
The specification discloses VNARs in table 1 (p.13-14). These all target either TfR-1 or CD98hc and so are not a description of any antibody which may provide the claimed function by targeting something other than these two targets. Moreover, some of these antibodies appear highly similar. For example, TXB4 (Clone 18; SEQ ID NO: 2) differs by only two residues to Clone C (SEQ ID NO: 3). In contrast, SEQ ID NO: 4 and SEQ ID NO: 5 differ significantly in CDR3. Thus, there does not appear to be any common structure which confers the claimed properties and so the analysis turns to whether the disclosed antibodies are “representative” of the genus.
The instant specification reduces to practice TXB4, e.g., example 2 on p.36. The specification references other clones (table 1) as well as references other documents, such as WO2018/031424 (paragraph 16). However, in looking to ‘424, it is clear that this is an unpredictable art. Of over 1000 clones, only 51 unique sequences met the functional criteria (paragraph 91). Of those 51, eight were selected for further experiments while three were discarded because they only bound human while another was discarded because it also bound control protein (i.e., was non-specific). Thus, in a concerted screening effort it was demonstrated that some work and some don’t. Paragraph 93 notes that 242 of the clones shared identical CDR3 regions and states “binding affinity to TfR1 alone was not enough to confer brain penetration by phages”. Further, the disclosure of one particular VNAR does not describe the sequence of any other VNAR. For example, given the disclosure of Clone C or Clone H, one could not envisage the sequence of VNAR-txp1.
Overall, there are innumerable VNARs that might have the properties claimed by applicant. As stated in MPEP §2163, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). MPEP §2163 also states that to meet the written description requirement under the “representative number” standard, “depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed”.
There does not appear to be any predictability regarding a specific sequence and whether or not that VNAR has the claimed properties (no common structure). Further, while it is appreciated that certain VNARs are disclosed with the required functions, this does not adequately represent the vast number of potential species within the claimed genus. Without any way to determine how broad the genus of such antibodies is, there is no way to determine if these antibodies represent the full breadth of what is claimed. The disclosure of these specific antibodies would not convey to the artisan that Applicant was in possession of the full genus of all antibodies which possess the required functions, does not allow the skilled artisan to envisage the specific structure of such antibodies, and does not convey that Applicant was in possession of the “necessary common attributes” to represent the genus.
Further note the decision in Amgen v. Sanofi 2017, where the Court supported previous decisions (Centocor 2011; Abbvie 2014) that defining an antibody solely by what it binds does not satisfy the written description requirement, stating that this would allow patentees to “claim antibodies by describing something that is not the invention, i.e., the antigen”.
The same rationale applies to the claimed “variants” of claim 3. Under the broadest reasonable interpretation (see §112b rejection above), this includes making any number of changes without restriction to the parent sequence including wholly changing the CDRs. While certain variants are described, these variants are not commensurate in variability with that of the genus being claimed.
Therefore, claims 1-3, 6, 8, 11, 14-18, 20, 24, 27-29 do not meet the written description requirement.
Claims 15-17 and 20 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.
Claim 15 recites the genus of “a condition which responds to activation of a neurotrophin receptor”. This is not an established or well-known genus of conditions. Other than the name of the genus, there is no disclosed shared characteristic which would define which conditions are members of this genus and the specification does not appear to disclose any species to represent this genus. Given the evidence of record and taking the disclosure into account, the skilled artisan could not immediately envisage which conditions are members of the claimed genus and which are not.
Therefore, claims 15-17 and 20 do not meet the written description requirement. Note that claim 18 is not included in this rejection as the disease being treated is a neurodegenerative disease or condition, which are well-established in the art.
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.
Claim(s) 1-3, 8, 11, 14-18, 20, 24, 27-29 are rejected under 35 U.S.C. 103 as being unpatentable over Stocki (WO2018031424; form 892) in view of Lerner (WO2017192538; form 892).
Stocki is concerned with using VNARs to transport therapeutics across the blood-brain barrier (BBB) (abstract; paragraph 13). Stocki teaches a conjugate of a therapeutic agent (rituximab) to a VNAR (paragraph 46), which demonstrates brain uptake (paragraph 51). Stocki demonstrates this also works when coupled with IDUA (paragraph 52) and neurotensin (paragraph 54). Stocki teaches the use of this composition for coupling to antibodies to treat neurodegeneration (paragraph 130). Stocki does not teach the therapeutic is a TrkB agonist antibody.
Lerner teaches TrkB agonist antibodies for treating neurodegenerative disorders (title). Lerner teaches conjugating the TrkB agonist antibody to a targeting moeity which directs the therapeutic to the brain (paragraph 84).
Regarding claim 1, it would have been obvious to one of ordinary skill in the art at the time of filing to substitute the therapeutic of Stocki with a TrkB agonist antibody as in Lerner, arriving at the instant invention. Both Stocki and Lerner are concerned with delivering therapeutics to the brain as well as conjugations of delivery/therapeutic compositions. Stocki provides a VNAR which successfully delivers antibodies to the brain, which is a stated goal of Lerner. One would have had a reasonable expectation of success in achieving the claimed property of “capable of uptake across a mammalian blood brain barrier” as Stocki demonstrates this property with other antibodies.
Regarding claim 2, Stocki teaches the same VNARs as in instant claim 3, e.g., clone C (paragraph 245). Claim 2 describes a property of the VNAR domain and an identical composition must have the same inherent properties.
Regarding claim 3, Stocki teaches the VNAR is Clone C (paragraph 245; example 8).
Regarding claim 8, Stocki teaches administering additional TfR binding compounds (VNARs) (paragraph 222) and teaches conjugates with more than one binding specificity (paragraph 87). This would have made including an additional VNAR obvious. Further, duplication of parts—such as having a second VNAR in the conjugate—is prima facie obvious (MPEP §2144.04(VI)). While the claim requires the VNARs are independent, the claim does not require the VNARs to be structurally different or to have a different target, i.e., duplicating the first VNAR is within the scope of two independent VNAR domains.
Regarding claim 11, Stocki teaches combination with additional therapeutics as well as diagnostic agents (paragraph 87) and states this can be one or more therapeutic/diagnostic agents in the same conjugate (paragraph 164), rendering this arrangement obvious.
Regarding claim 14, Stocki teaches the conjugate as a pharmaceutical composition (paragraph 188) as does Lerner (paragraph 85).
Regarding claims 15 and 18, Lerner teaches the TrkB agonist antibody to treat Alzheimer’s disease (paragraph 79). It would have been obvious to use the conjugate as described above to treat Alzheimer’s because the therapeutic of Lerner is a known therapeutic for Alzheimer’s that needs to reach the brain and the VNAR of Stocki delivers that therapeutic to the brain. As Alzheimer’s disease is listed in instant claim 18, which depends from claim 15, Alzheimer’s disease must also meet the limitations of the treated disease in claim 15.
Regarding claim 16, Lerner teaches intravenous administration (paragraph 90) as does Stocki (paragraph 205-206).
Regarding claim 17, this claim is directed to a result of the administration itself and not an active step. Administering the same drug to the same person to treat the same disease must achieve the same results. Further, delivery to the brain would have been expected as described above.
Regarding claim 20, using a VNAR that binds TfR-1 such as clone C is discussed as above; see also Stocki paragraph 289. Using two copies of the VNAR would have been obvious as above; see discussion of claim 8. Using a TrkB agonist antibody would have been obvious as described above. As instant claim 20 is a combination of previously discussed claims, those claim limitations would have been obvious for the same reasons.
Regarding claim 24, the neurons of the subject would be contacted with the conjugate as described above. Instant claim 24 recites an effect of this administration and would be achieved with the method as described above. Moreover, Lerner teaches this effect using the TrkB agonist antibody (claim 25).
Regarding claims 27-29, Lerner teaches a polynucleotide (nucleic acid) encoding the composition encoded in a vector (claims 23-24) as well as placing that vector in a host cell (paragraph 71). Stocki also teaches this arrangement of nucleic acid/vector/host cell (claims 18-20). Thus, such a composition would have been obvious.
Therefore, claims 1-3, 8, 11, 14-18, 20, 24, 27-29 would have been obvious.
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Stocki and Lerner as applied to claim 1-3, 8, 11, 14-18, 20, 24, 27-29 above, and further in view of Mi (US20100297121; form 892).
The teachings of Stocki and Lerner are described above and incorporated herein. While Lerner would have made obvious a TrkB agonist antibody, Lerner does not teach that this antibody is 29d7.
Nevertheless, selecting 29d7 as the antibody would have been obvious. Given the teachings above, one would have found it obvious to select a known TrkB agonist antibody, in particular one which demonstrates benefits to CNS neurons and is taught as treating Alzheimer’s disease for the reasons described above. Mi teaches 29D7 is a TrkB agonist antibody (paragraph 142) and teaches administering the antibody to a subject with Alzheimer’s disease (claim 106) to promote neuronal survival (claim 6). This provides a reasonable expectation that the specific TrkB agonist antibody 29D7 will accomplish the therapeutic effects desired by administering a TrkB agonist antibody as described by Lerner.
Therefore, claim 6 would have been obvious.
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, 6, 8, 11, 14-18, 20, 24, 27-29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12351642 in view of Lerner and Mi. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claim 1 is a conjugate of a VNAR which passes the BBB and a TrkB agonist antibody, including variants of Clone C and Clone H (instant claim 3). The reference document claims such conjugated variants, e.g., claim 1, 2, 5, 8, 9, 10, but differs in that the reference claims do not specify the therapeutic is a TrkB agonist antibody nor specifically 29D7. Nevertheless, this would have been an obvious variation. The reference claims explicitly state that the VNAR transports across the BBB and may be operably linked to a heterologous molecule such as a therapeutic. Reference claim 9 claims treatment of a CNS disease. One of ordinary skill in the art would have found it obvious to choose a particular therapeutic for transport within this generic genus. Lerner provides the teachings and motivations to select a TrkB agonist antibody as the therapeutic and Mi teaches 29D7 is such an antibody as described above and incorporated herein.
Claims 1-3, 6, 8, 11, 14-18, 20, 24, 27-29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11097010 in view of Lerner and Mi. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claim 1 is a conjugate of a VNAR which passes the BBB and a TrkB agonist antibody, including variants of Clone C and Clone H (instant claim 3). The reference document claims such conjugated variants, e.g., claims 1, 2, 3, 5, 8, 9 but differs in that the reference claims do not specify the therapeutic is a TrkB agonist antibody nor specifically 29D7. Nevertheless, this would have been an obvious variation. The reference claims explicitly state that the VNAR transports the therapeutic to the brain and may be linked to a therapeutic. Reference claim 18 claims treatment of a disease by delivering a therapeutic to the brain. One of ordinary skill in the art would have found it obvious to choose a particular therapeutic for transport within this generic genus. Lerner provides the teachings and motivations to select a TrkB agonist antibody as the therapeutic and Mi teaches 29D7 is such an antibody as described above and incorporated herein.
Claims 1-3, 6, 8, 11, 14-18, 20, 24, 27-29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11766482 in view of Lerner and Mi. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claim 1 is a conjugate of a VNAR which passes the BBB and a TrkB agonist antibody, including variants of Clone C and Clone H (instant claim 3). The reference document claims nucleic acids encoding such variants, e.g., claims 1 and 7, but differs in that the reference claims do not specify the therapeutic is a TrkB agonist antibody nor specifically 29D7. Nevertheless, this would have been an obvious variation.
The reference claims are limited to nucleic acids, which meets the limitations of instant claim 27. Further, where the reference claims are to a composition, the specification may be reviewed for the disclosed uses of that composition. See the decisions in Sun Pharmaceuticals v Eli Lily Fed Cir July 28, 2010; Geneva v GlaxoSmithKline 349, F.3d 1373; and Pfizer v Teva 518 F3d 1353 supporting the Office’s use of disclosed utilities of compositions when applying double patenting rejections to method claims. Further, those portions of the specification which provide support for the patent claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the patent. In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970). The court in Vogel recognized ‘that it is most difficult, if not meaningless, to try to say what is or is not an obvious variation of a claim,’ but that one can judge whether or not the invention claimed in an application is an obvious variation of an embodiment disclosed in the patent which provides support for the patent claim. According to the court, one must first ‘determine how much of the patent disclosure pertains to the invention claimed in the patent’ because only ‘[t]his portion of the specification supports the patent claims and may be considered.’ The court pointed out that ‘this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined.’’’ MPEP §804(II)(B)(1)
The nucleic acid encodes a VNAR polypeptide fused to a therapeutic (reference claim 8). That polypeptide is disclosed as passing the blood brain barrier to deliver a therapeutic to the brain (abstract). The specification also supports that the claimed sequences in, e.g., reference claim 1 and 2, meet the limitations of “Clone C or one of its variants”; see e.g., table 5 and the preceding paragraph. One of ordinary skill in the art would have found it obvious to choose a particular therapeutic for transport within this genus. Lerner provides the teachings and motivations to select a TrkB agonist antibody as the therapeutic and Mi teaches 29D7 is such an antibody as described above and incorporated herein.
Claims 1-3, 6, 8, 11, 14-18, 20, 24, 27-29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-12, 20-27, and 34-36 of copending Application No. 18684463 in view of Lerner and Mi.
Instant claim 1 is a conjugate of a VNAR which passes the BBB and a TrkB agonist antibody, including variants of Clone C and Clone H (instant claim 3). The reference document claims such variants, e.g., claims 34, 9, and 10, but differs in that the reference claims do not specify the therapeutic is a TrkB agonist antibody nor specifically 29D7. Nevertheless, this would have been an obvious variation.
While the reference claims do not claim a method of treatment, where the reference claims are to a composition (such as claim 34), the specification may be reviewed for the disclosed uses of that composition. See the decisions in Sun Pharmaceuticals v Eli Lily Fed Cir July 28, 2010; Geneva v GlaxoSmithKline 349, F.3d 1373; and Pfizer v Teva 518 F3d 1353 supporting the Office’s use of disclosed utilities of compositions when applying double patenting rejections to method claims. Further, those portions of the specification which provide support for the patent claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the patent. In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970). The court in Vogel recognized ‘that it is most difficult, if not meaningless, to try to say what is or is not an obvious variation of a claim,’ but that one can judge whether or not the invention claimed in an application is an obvious variation of an embodiment disclosed in the patent which provides support for the patent claim. According to the court, one must first ‘determine how much of the patent disclosure pertains to the invention claimed in the patent’ because only ‘[t]his portion of the specification supports the patent claims and may be considered.’ The court pointed out that ‘this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined.’’’ MPEP §804(II)(B)(1)
The VNAR polypeptide conjugated to a therapeutic antibody (reference claim 10) is disclosed as passing the blood brain barrier to deliver a therapeutic to the brain (abstract). The specification also supports that the claimed sequences in, e.g., reference claim 1 and 2, meet the limitations of “Clone C or one of its variants”; see e.g., paragraph 103. One of ordinary skill in the art would have found it obvious to choose a particular therapeutic for transport within this genus. Lerner provides the teachings and motivations to select a TrkB agonist antibody as the therapeutic and Mi teaches 29D7 is such an antibody as described above and incorporated herein.
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 6, 8, 11, 14-18, 20, 24, 27-29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 18977734 in view of Lerner and Mi.
Instant claim 1 is a conjugate of a VNAR which passes the BBB and a TrkB agonist antibody, including variants of Clone C and Clone H (instant claim 3). The reference document claims such variants, e.g., claims 1-4, but differs in that the reference claims do not specify the therapeutic is a TrkB agonist antibody nor specifically 29D7. Nevertheless, this would have been an obvious variation.
The VNAR polypeptide conjugated to a therapeutic antibody (reference claim 1) is claimed as passing the blood brain barrier to deliver a therapeutic to the brain (reference claim 6). One of ordinary skill in the art would have found it obvious to choose a particular therapeutic for transport within this genus. Lerner provides the teachings and motivations to select a TrkB agonist antibody as the therapeutic and Mi teaches 29D7 is such an antibody as described above and incorporated herein.
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 6, 8, 11, 14-18, 20, 24, 27-29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 12187805 in view of Lerner and Mi. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claim 1 is a conjugate of a VNAR which passes the BBB and a TrkB agonist antibody, including variants of Clone C and Clone H (instant claim 3). The reference document claims such conjugated variants, e.g., claim 1, 2, 5, 8, 9, 10, but differs in that the reference claims do not specify the therapeutic is a TrkB agonist antibody nor specifically 29D7. Nevertheless, this would have been an obvious variation. The reference claims explicitly state that the VNAR transports across the BBB and may be operably linked to a heterologous molecule such as a therapeutic. Reference claim 16 claims treatment of a CNS disease. One of ordinary skill in the art would have found it obvious to choose a particular therapeutic for transport within this generic genus. Lerner provides the teachings and motivations to select a TrkB agonist antibody as the therapeutic and Mi teaches 29D7 is such an antibody as described above and incorporated herein.
Allowable Subject Matter
No claim is allowed. However, Applicant’s elected species of VNAR-txp1 (SEQ ID NO: 6) effective filing date 11/20/2020) represents allowable subject matter. As noted in the specification, the first disclosure of this sequence appears to be the unpublished US application 63/112314, which is not a valid prior art document. This sequence is disclosed in US 20250122298, WO2024107749, and WO2022103769, but these documents also do not qualify as prior art under either §102a1 or §102a2. As noted above, the VNAR is an antibody, where it is well-established that the sequence of such an antibody is unpredictable. Thus, without clear teachings or motivations to arrive at SEQ ID NO: 6, this represents a non-obvious sequence.
Conclusion
Claim 6 recites antibody 29D7. This antibody appears well-documented and publicly available and so no enablement rejection regarding a biological deposit was made.
WO2024107749 has not been filed as a US application and so no double patenting rejection is made over this document.
Application 63/112314 does not appear to be the subject of a non-provisional US application and so no double patenting rejection is made over this document.
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/Adam Weidner/ Primary Examiner, Art Unit 1675