DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-39 are pending. Claims 5-39 are withdrawn. Claims 1-4 are presently considered.
Election/Restrictions
Applicant’s election without traverse of Group I (affinity polypeptides, original claims 1-19) and the species of SEQ ID NO: 3 in the reply filed on 1/14/2026 is acknowledged.
The originally elected species of SEQ ID NO: 3 has the following sequence:
AVAQSFNMQQQRRFYEALHDPNLTEEQRNAKIQSIRDDAVAQSFNMQCQRRFYEALHDPNLTEEQRNAKIQSIRDDCAVAQSFNMQQQRRFYEALHDPNLTEEQRNAKIQSIRDDAVAQSFNMQCQRRFYEALHDPNLTEEQRNAKIQSIRDDCAVAQSFNMQQQRRFYEALHDPNLTEEQRNAKIQSIRDDAVAQSK
The highlighted text represents subunits of SEQ ID NO: 17, which has the sequence of
FNMQQQRRFYEALHDPNLTEEQRNAKIQSIRDD.
The underlined portions represent instant SEQ ID NO: 19 (AVAQS), and the remainder represents SEQ ID NO: 18, which has the of
FNMQCQRRFYEALHDPNLTEEQRNAKIQSIRDDC.
The originally elected species is understood to read upon instant claims 1-4, but not claims 5-19 (see, e.g., Reply filed 1/14/2026 at 2 at 2nd ¶).
Following extensive search and examination, the originally elected species consisting of SEQ ID NO: 3 was deemed free of the prior art. Per MPEP § 803.02(III)
If the examiner determines that the elected species is allowable over the prior art, the examination of the Markush claim will be extended. If prior art is then found that anticipates or renders obvious the Markush claim with respect to a nonelected species, the Markush claim shall be rejected; claims to the nonelected species would still be held withdrawn from further consideration. The prior art search will not be extended unnecessarily to cover all nonelected species.
Accordingly, Examination was extended to a non-elected species consisting of SEQ ID NOs: 1-2 and 4-16, which were all subsequently deemed free of the prior art.
Examination was then extended to non-elected species sharing 90% sequence identity with instant SEQ ID NO: 3, and species within this subgenus were subsequently deemed obvious in view of the prior art as applied below.
Claims 20-39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1/14/2026.
Claims 5-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 1/14/2026.
Claims 1-4 are presently examined.
Priority
The priority claim to Provisional 62/971509 (filed 2/07/2020) is acknowledged.
Information Disclosure Statement
The IDS filed 3/08/2023 is acknowledged and presently considered.
Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Claim 1 is representative of the pending claim scope and the applicable claim interpretation is discussed below.
The claims recite “at least about”. The term “about” is undefined on record. The term “about” lacks an exact meaning in the prior art and may reasonably mean ±5%, ±10%, ±20%, within “5-fold of a value” or even “within an order of magnitude”, etc. (see, e.g., US8008449B2 at col. 18 at lines 19-33, noting that “particularly with respect to biological systems or processes, [about] can mean up to an order of magnitude or up to 5-fold of a value”; see also US20180162942A1 at ¶[0108], defining “about” to include an order of magnitude or 5-fold of a value). For purposes of examination in view of the prior art, “about” has been reasonably interpreted to mean ±10%, which consistent with the prior art and instant record, and is reasonable in view of the increments disclosed (see, e.g., Spec. filed 9/13/2023 at 4 at lines 10-20, p. 5 at lines 4-10, noting that the difference between “about 90%” and “about 97%” would be rendered substantially moot if “about” meant an order of magnitude or 5-fold).
At claims 4-16, the reference to a specific sequence (i.e., SEQ ID NOs: 1-16), the variability of the genus (i.e., “at least about 90% identity to” the specific sequence), and the recitation of cysteine residues at particular positions is understood as follows: The positions referenced at claims 4-16 are understood to specifically refer to the exact sequence identified in each claim (e.g., SEQ ID NO: 3 at claim 4), and the requirement for cysteine residues to exist is understood to limit the scope of embodiments having “at least about 90% identity” to such sequences sharing “at least 90% sequence identity” that also possess cysteine residues at the specific positions recited (i.e., claim 4 is limited to sequences having “at least about 90%” identity to SEQ ID NO: 3, and also simultaneously have cysteine residues at the positions of 48, 77, 125, and 154 of the structures of the final “Affinity polypeptide ligand”).
Additional claim interpretations are set forth below.
Claim Rejections
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 1-4 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.
Claims 1 and 4 recite “at least about 90%”, which is indefinite because it conflates qualitative and quantitative language. Specifically, it is unclear if values such as 80%, 83%, 84%, 89.9%, etc. are included or excluded by the phrase, since such values are “about 90%” but not “at least” 90%. Close prior art exists on record (see rejections under 35 USC 103, below) and such differences materially and substantially alter the pending claim scope. Applicant could overcome this rejection by removing the term “about” from the claims.
Claim 1 recites “wherein residues at positions 5 and 34 are cysteine”, which lacks antecedent basis in context because three distinct sets of sequences are recited at claim 1, and it is unclear which positions of which sequence is being referenced. More specifically, the claim recites (i) a genus of “affinity polypeptide ligand”, (ii) a subgenera of polypeptide subunit sequences having “at least about 90% sequence identity to SEQ ID NO: 17”, and (iii) a subgenera of polypeptide subunit sequences having “at least about 90% sequence identity to SEQ ID NO: 18”. Because sequences sharing at least 90% sequence identity to SEQ ID NOs: 17 and 18 may have at least 3 altered residues1 relative to the base sequence (e.g., substitutions, deletions, insertions), this ostensibly means that (a) Subunit-1 and Subunit-2 may vary in length from at least 30-36 amino acids due to insertions and deletions, (b) both Subunit-1 and Subunit-2 may therefore comprise two or more Cys residues due to permissible substitutions, and that (c) references to sequence positions may be made relative to the overall Affinity polypeptide ligand, Subunit-1, Subunit-2, or SEQ ID NO: 18. Accordingly, the pending claim scope is rendered indefinite because the reference to “wherein residues at positions 5 and 34 are cysteine” may be reasonably interpreted as referring to the claimed “Affinity polypeptide ligand”, SEQ ID NO: 18, or either Subunit. For example, the following provide different reasonable interpretations of the phrase “wherein residues at positions 5 and 34 are cysteine” that alter the pending claim scope:
wherein residues at positions 5 and 34 relative to SEQ ID NO: 18 are cysteine
wherein residues at positions 5 and 34 of the affinity polypeptide ligand are cysteine
wherein residues at positions 5 and 34 of Subunit-2 are cysteine.
Accordingly, there are multiple, reasonable interpretations, which each impact the scope of the instant claims. Because there are multiple, reasonable interpretations, the scope of instant claim 1 is rejected as indefinite.
The scope of claim 1 recites arbitrary and conflicting structural limitations, which render the claim scope indefinite. Specifically, instant claim 1 recites and requires
An affinity polypeptide ligand comprising: one to ten of Subunit-1….one to ten of Subunit-2….wherein the ligand comprises at least two of Subunit-1 or at least two of Subunit-2, wherein at least one Subunit-1 would be between any two of Subunit-2.
This is problematic because the scope of Subunit-1 and Subunit-2 materially and substantially overlap because Subunit-1 may be any sequence sharing “at least about 90% identity to SEQ ID NO: 17” and Subunit-2 may be any sequence sharing “at least about 90% identity to SEQ ID NO: 18”. Critically, SEQ ID NO: 17 shares 96.97% identity with SEQ ID NO: 18:
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Over the length of SEQ ID NO: 18, the two sequences share 32/34 residues, or 94.1% identity. Accordingly, Subunit-1 and Subunit-2 are defined in a manner wherein the scope of both materially and substantially overlap, such that the designation and distinction of both subunits becomes arbitrary. For example, the following sequence comprises four consecutive repeats of instant SEQ ID NO: 18 (i.e., Subunit-2), which is also four consecutive repeats of a sequence sharing 94.1% sequence identity with SEQ ID NO: 17 (Subunit-1):
FNMQCQRRFYEALHDPNLTEEQRNAKIQSIRDDCFNMQCQRRFYEALHDPNLTEEQRNAKIQSIRDDCFNMQCQRRFYEALHDPNLTEEQRNAKIQSIRDDCFNMQCQRRFYEALHDPNLTEEQRNAKIQSIRDDC
This exact sequence may be simultaneously, correctly, and arbitrarily described as
(1) (Subunit-2)4,
(2) (Subunit-1)4,
(3) (Subunit-1)2-(Subunit-2)2,
(4) (Subunit-2)2-(Subunit-1)2,
(5) (Subunit-1)3-(Subunit-2),
(6) (Subunit-2)3-(Subunit-1),
(7) (Subunit-1)-(Subunit-2)-(Subunit-1)-(Subunit-2),
(8) (Subunit-2)-(Subunit-1)-(Subunit-2)-(Subunit-1),
(9) (Subunit-2)-(Subunit-1)2-(Subunit-2), or
(10) (Subunit-1)-(Subunit-2)2-(Subunit-1)
However, due to the structural limitations requiring
An affinity polypeptide ligand comprising: one to ten of Subunit-1….one to ten of Subunit-2….wherein the ligand comprises at least two of Subunit-1 or at least two of Subunit-2, wherein at least one Subunit-1 would be between any two of Subunit-2.
only the characterizations of (5), (7), (8), and (9) would ostensibly read upon the instant claims, but the characterizations of (1), (2), (3), (4), (6), and (10) would be excluded from the pending claim scope. Accordingly, it is unclear if such sequences are excluded from the pending claim scope since they may be interpreted in a manner that does not satisfy the limitations of instant claim 1, or if the claim scope includes such embodiments since they may be interpreted in a manner consistent with the limitations of claim 1. Stated alternatively, the limitations regarding sequence identity of each Subunit are discordant with respect to subsequent structural limitations that ostensibly require a distinct and separate “Subunit-1” and “Subunit-2” to exist; this failure of correspondence between limitations creates ambiguity in claim scope, because it is unclear if an embodiment that does not clearly satisfy the structural limitations (e.g., when distinct and separate subunits cannot be unambiguously identified) is included or excluded from the claim scope. This creates an improper “zone of uncertainty” that fails to inform “with reasonable certainty” those of skill in the art the metes and bounds of the instant invention, and therefore such language is rejected as indefinite because it cannot be said to reasonably satisfy the public notice function of 35 USC 112(b) (see, e.g., Nautilus, Inc. v. Biosig Instruments, Inc., 134 S. Ct. 2120, 2130 (2014)). Applicant may overcome this rejection as follows: Applicant may remove the “at least about 90% identity” language from all claims, such that the claim scope is limited to embodiments comprising SEQ ID NO: 17 and 18, such as SEQ ID NOs: 1-16.
Claim 3 recites a product and process step using the product within the same claim, which renders the claim scope indefinite (see, e.g., MPEP § 2173.05(p)(II)), because it is unclear if infringement of the product occurs before, during, or after the completion of the active method (see claim 3, requiring that a C-terminal amino acid “immobilizes the ligand to a solid support”). For purposes of examination, a solid support is not part of the originally elected species, and therefore examination is based upon the understanding that instant SEQ ID NOs: 1-16 necessarily and inherently comprise the C-terminal amino acid structure required to complete this active method step). Applicant may overcome this rejection as follows: Applicant may delete claim 3 or clarify the structure required to achieve the immobilization to a solid support by reference to a specific C-terminal sequence or modification.
Claims 4 recite a product and process steps using the product within the same claim, which renders the claim scope indefinite (see, e.g., MPEP § 2173.05(p)(II)), because it is unclear if infringement of the product occurs before, during, or after the completion of the active method (see claim 4, reciting that “a disulfide bond is formed”). Applicant could overcome this rejection by amending the claims to change the phrase “wherein a disulfide bond is formed” to “wherein a disulfide bond exists between…” or “wherein the ligand has a disulfide bond between…”.
Claims 2-4 depend upon an indefinite base claim and fail to reconcile the indefiniteness of the base claim, accordingly, claims 2-16 are rejected as indefinite for the reasons applied to the base claim.
Claims 1-4 are rejected.
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 4 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 4 depends from instant claim 1, and claims 1 and 4 have been rejected as indefinite (see rejections under 35 USC 112(b), above). For purposes of the instant rejection, the recitation at claim 1 of “wherein residues at positions 5 and 34 are cysteine, wherein there is a disulfide bond between the two cysteine residues” is reasonably inferred to refer to the positions of the claimed product, namely the “affinity polypeptide ligand”. However, claim 4 unambiguously reads upon and encompasses instant SEQ ID NO: 3, but SEQ ID NO: 3 lacks a Cysteine at least at position 5, and therefore reasonably appear to be excluded from the scope of instant claim 1. Accordingly, claim 4 is rejected for failing to clearly and unambiguously include all the limitations of the claim upon which it depends.
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.
Claim 4 is rejected.
Claim Rejections - 35 USC § 112(a), Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-4 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.
The legal analysis for determining whether or not a disclosure satisfies the written description requirement is set forth at MPEP § 2163.
The term polypeptide is distinguished form the term “polypeptide affinity ligand” and “affinity polypeptide ligand” on record (see, e.g., Spec. filed 9/13/2022 at 3 at line 25 to page 4 at line 10) (see, e.g., Nystrom v. TREX Co., Inc., 424 F. 3d 1136, 1143 (Fed. Cir. 2005), explaining that "When different words or phrases are used in separate claims, a difference in meaning is presumed"). Accordingly, the difference in these terms from “polypeptide” is the functionality identified (e.g., “affinity ligand”). Therefore, the relevant issue is that the pending claims recite a functional limitation, namely the claims are not directed to polypeptides satisfying the structural requirements of claims 1-4, but rather the claims are only directed to embodiments that are “affinity polypeptide ligands” that also satisfy the structural limitation set forth in the claims. This is pertinent because the structural limitations of claims 1-2 and 4 ostensibly encompass >>trillions of polypeptides2, but it is unclear which of these structures are capable of acting as an “affinity polypeptide ligand” as required by the claims.
The functionality required to constitute an “affinity polypeptide ligand” is not specifically disclosed in a structure/function relationship commensurate in scope with the instant claims on record, but the term is understood to include sequences that “specifically binds analytes, e.g., immunoglobulin proteins” (see, e.g., Spec. filed 9/13/2022 at 3 at lines 25-31), and sequences having “superior affinity for analytes, while providing stability of a ligand over a wide pH range (3-13)” (see, e.g., Spec. filed 9/13/2022 at 4 at lines 20-21), and sequences capable of use in a solid support having a “capacity of greater than about 30 g/L” (see, e.g., Spec. filed 9/13/2022 at 10 at lines 15-21). However, it is prima facie unclear which of the trillions of polypeptides within the scope of instant claims 1-4 do or do not act as an “affinity polypeptide ligand” as required by the claim scope.
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus (see, e.g., MPEP § 2163(II)(3)(a), MPEP §2163.03(V)). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. Notably, the disclosure appears to test and reduce to practice a single sequence with specificity, that was shown to have the required functionality, namely instant SEQ ID NO: 3 (see, e.g., Spec. filed 9/13/2022 at 3 at lines 1-15, Figs. 1-4). Additional sequences were disclosed on record, but do not appear to have been specifically tested (e.g., instant SEQ ID NOs: 1-2 and 4-16). Even assuming arguendo that each of SEQ ID NOs: 1-16 were “affinity polypeptide ligands” having the requisite functionality, each of these sequences comprise repeats consisting only of sequences comprising instant SEQ ID NOs: 17, 18, and 19 without any variation. Therefore, even if the limited testing was extended to all explicitly disclosed sequences, the instant disclosure fails to provide any additional guidance regarding what structures and variations are permissible within such sequences without abrogating the required functionality. Although the MPEP does not define what constitutes a sufficient number of representative species, the Courts have indicated that the disclosure of two species within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618. Similarly, the disclosure of zero embodiments lacking 100% sequence identity to instant SEQ ID NOs: 17, 18, and 19 does not provide sufficient disclosure to satisfy the written description requirement for the instantly claimed genus.
In the absence of a reduction to practice of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. Here, the Specification identifies that the claimed structures contain cysteine amino acids, and that “[t]he cysteine amino acids which form a disulfide bond are typically about 28 amino acid residues apart from one another”, that “there is about one disulfide bond for every about 80-125 amino acids of a ligand”, and that “disulfide bonds stabilize the helical nature of the polypeptide ligand” (see, e.g., Spec. filed 9/13/2022 at 3 at lines 25 to page 4 at line 10). Critically, such limitations are not actually recited in the pending claims, which actually do not limit cysteine amino acids from being directly adjacent to one another or otherwise within less than 28 amino acids (compare id. with instant claims 1-4, noting that sequence identity does not limit the placement of cysteine substitutions or insertions).
The functional limitation is not disclosed as a structure/function relationship, but rather appears to be repeatedly disclosed and described only as something that the inventors hope and desire to achieve (see, e.g., Spec. filed 9/13/2022 at 3 at lines 25-31, disclosing hoped-for result, namely sequences having “superior affinity for analytes, while providing stability of a ligand over a wide pH range (3-13)”; see, e.g., Spec. filed 9/13/2022 at 4 at lines 20-21, disclosing a hoped for result with no structure/function relationship).
Accordingly, the functional limitation is only utilized in the claims as a vague attempt to capture unknown and undisclosed structures, sufficient to achieve some functional result that Applicant hopes and desires that the disclosed invention is able to achieve. However, the disclosure but does not meaningfully disclose an unambiguous structure/function relationship permitting an artisan to identify, a priori, which exact structures, from among >trillions of sequence, do or do not satisfy the functional limitations at issue.
Accordingly, the basic question of “what sequences from among the >trillions that satisfy the structural limitations of claim 1 actually satisfy the functional requirements?” is left unanswered.
Although the level of skill in the art is high, the predictability in the art is low due to the complexity of biological systems, biochemistry, and polypeptide biophysics. Specifically, an artisan would not be able to predict or identify, a priori, and in the absence of any guidance or consensus structures exactly what polypeptide, from among trillions potentially claimed, do or do not constitute affinity ligands. Therefore, in the absence of sufficient structure/function teachings identifying particular compounds capable of affinity ligands, as required to practice the full scope of the claims, an artisan would not reasonably conclude that Applicant possessed the full scope of the broad and highly varied claim scope.
Conclusion
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). The courts have stated that “merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus” (see, e.g., AbbVie v. Janssen, 111 USPQ2d 1780 (Fed. Cir. 2014) at 1789). In addition, the Courts have stated
“[r]egardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
This is pertinent because, in the instant case, Applicants have claimed a broad and highly varied genus comprising an unknown number of species defined by reference to one or more functional limitations; however, the originally filed disclosure has failed to identify any common structure/function relationship sufficient to permit an artisan to identify what structures are included or excluded by the claim scope. This also means that it is prima facie unclear what structures are infringe or do not infringe upon the pending claim scope.
In conclusion, for the reasons discussed above, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention.
Claims 1-4 are rejected.
Claim Rejections - 35 USC § 103
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.
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 1 is rejected under 35 U.S.C. 103 as being unpatentable over US2019/0167576A1 (Jun. 6, 2019).
Claim Interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Claim 1 has been rejected as indefinite. For purposes of the instant rejection, claim 1 is understood to read upon any sequences that may be interpreted, arbitrarily, to satisfy the limitations of claim 1. Additional claim interpretations are set forth below.
US’576 pertains to “anchor molecules” that bind to antibody products with high affinity (see, e.g., US’576 at title, abs). Regarding the instant claims and polypeptide products comprising multiple antibody binding domains consecutively, US’576 generally teaches and discloses the creation of Fusion Proteins comprising multiple individual binding domains (see, e.g., US’576 at ¶[0029], Fig. 16, reproduced below:
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Accordingly, artisans knew, circa 2019, that “High affinity monoclonal antibody product binders” could “comprise one or more binding domains, e.g., 2, 3, 4 or more binding domains”, wherein the “fusion compounds” could be “composed of similar or dissimilar high affinity monoclonal antibody product binders” (see, e.g., US’576 at ¶¶[0029], [0125], Fig. 16; see also id. at ¶[0126], explaining that the “domain can be repeated forming a fusion protein of 2 or more minimized domains”). Regarding instant claim 1 and SEQ ID NO: 17 and SEQ ID NO: 18, US’576 identifies exemplary “high affinity binders” including SEQ ID NO: 2 (see, e.g., US’576 at ¶[0115], Table 1 at ¶[0116], SEQ ID NO: 2), which has the sequence of FNMQCQRRFYEALHDPNLNEEQRNAKIKSIRDDC (see id.), which shares over 90% sequence identity with instant SEQ ID NO: 18:
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And also shares over 90% sequence identity with instant SEQ ID NO: 17:
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Accordingly, prior art SEQ ID NO: 2 is understood to satisfy the requirements of both instant Subunit-1 and Subunit-2, simultaneously, and therefore distinctions between the two Subunits becomes arbitrary. Regarding the disulfide bond, US’576 explicitly teaches that SEQ ID NO: 2 is a “Cysteine Stabilized” version of the minimized Z-domain, and it is therefore understood to comprise a stabilizing disulfide bond between positions 5 and 34, where the cysteines are located (see, e.g., US’576 at ¶[0115], Table 1 at ¶[0116], SEQ ID NO: 2). Therefore, any limitations attempting to distinguish such domains from the prior art are understood to be arbitrary in view of the teachings of instant US’576. Regarding instant claim 1 and the structure of the “affinity polypeptide ligand”, an artisan would readily appreciate that SEQ ID NO: 2 of US’576 may simply be repeated “2, 3, 4 or more” times to predictably and expectedly create a fusion product comprising repeated domains of SEQ ID NO: 2 (see, e.g., US’576 at ¶¶[0029], [0125], Fig. 16), wherein such product would be readily understood to predictably and expectedly create a “High affinity monoclonal antibody product binders” (see, e.g., US’576 at ¶¶[0029], [0115], [0118], Table 1 at ¶[0116], Fig. 16; see also id. at ¶[0126], explaining that the “domain can be repeated forming a fusion protein of 2 or more minimized domains”; see also id. at ¶[0139], explaining how to create “a fusion protein of a number of repeating units”). Such a repeated sequence would necessarily comprise a Cys residue at positions 5 and 34 since the prior art sequence comprises Cys residues at these positions (see, e.g., US’576 at SEQ ID NO: 2 at positions 5 and 34).
The prior art of US’576 differs from instant claim 1 as follows: Although US’576 teaches and discloses fusion proteins comprising repeated domains, and discloses SEQ ID NO: 2, which satisfies the structural requirements at instant claim 1, US’576 does not actually reduce to practice a species of fusion protein comprising a repeated domains comprising SEQ ID NO: 2.
However, as noted above, US’576 explicitly teaches and directs artisans to make such fusion products (see, e.g., US’576 at ¶¶[0029], [0115], [0118], Table 1 at ¶[0116], Fig. 16; see also id. at ¶[0126], explaining that the “domain can be repeated forming a fusion protein of 2 or more minimized domains”; see also id. at ¶[0139], explaining how to create “a fusion protein of a number of repeating units”), and furthermore, an artisan would readily predict and expect that each repeat within the fusion proteins would have the affinity attributed to SEQ ID NO: 2 exactly as taught and disclosed by the prior art.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The claimed invention is the combination of prior art elements (e.g., SEQ ID NO: 2 of US’576) according to known methods of forming “High affinity monoclonal antibody product binders” comprising repeated binding domains as taught by US’576, to predictably and expectedly obtain a fusion protein having high affinity for antibody products (see, e.g., MPEP § 2143(I)(A), (D), (G)). Furthermore, each element would merely perform its art-recognized function in combination as it does separately.
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to make and synthesize a fusion protein containing repeats of a known prior art sequence.
Accordingly, claim 1 is rejected.
Claims 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over US2019/0167576A1 (Jun. 6, 2019) as applied to claim 1 above, and further in view of US6,013,763 (Jan. 11, 2000).
Claim Interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Claims 1-4 have been rejected as indefinite. For purposes of the instant rejection, claims 1-4 are understood to read upon any sequences sharing 90% identity with originally elected species of SEQ ID NO: 3. Additional claim interpretations are set forth below.
The teachings of US’576 as applied to instant claim 1 has been set forth above, and those teachings are incorporated into the instant rejection.
The teachings of US’576 differ from instant claims 1-4 and instant SEQ ID NO: 3 as follows: US’576 does not explicitly disclose a sequence sharing at least 90% sequence identity with instant SEQ ID NO: 3.
However, US’576 explicitly identifies and directs artisans to additional sequences that may be utilized in the disclosed inventions, including the sequences of US 6,013,763 (see, e.g., US’576 at ¶[0118], identifying US’763 as disclosing examples of “high affinity binding polypeptides” that may be used in the applications of US’576). This is pertinent because US’763 teaches and discloses SEQ ID NO: 35 (see, e.g., US’763 at SEQ ID NO: 35, col. 26 at line 10 to col. 28 at line 25; see also US’763 at col. 31 at line 61 to col. 32 at line 5). SEQ ID NO: 35 of US’763 has the sequence of AVAQSFNMQCQRRFYEALHDPNLNEEQRNAKIKSIRDDC (SEQ ID NO: 35 of US’927). Critically, regarding instant claims 1-2 and 4, “AVAQS” within instant SEQ ID NO: 35 of US’763 shares 100% sequence identity with the “spacer” of instant SEQ ID NO: 19 (compare instant SEQ ID NO: 19 with US’763 at SEQ ID NO: 35, showing 100% identity), and the remainder shares over 90% sequence identity with instant SEQ ID NO: 17:
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89
482
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And over 90% sequence identity with instant SEQ ID NO: 18:
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89
484
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In addition, it is noted that simply repeating SEQ ID NO: 35 of US’763 multiple times exactly as taught and suggested by the primary reference, yields the polypeptide such as
AVAQSFNMQCQRRFYEALHDPNLNEEQRNAKIKSIRDDCAVAQSFNMQCQRRFYEALHDPNLNEEQRNAKIKSIRDDCAVAQSFNMQCQRRFYEALHDPNLNEEQRNAKIKSIRDDCAVAQSFNMQCQRRFYEALHDPNLNEEQRNAKIKSIRDDCAVAQSFNMQCQRRFYEALHDPNLNEEQRNAKIKSIRDDCAVAQSFNMQCQRRFYEALHDPNLNEEQRNAKIKSIRDDCAVAQSFNMQCQRRFYEALHDPNLNEEQRNAKIKSIRDDC
Critically, such a “repeat” construct, created simply repeating the prior art sequence exactly as taught and suggested by the prior art, yields a sequence sharing over 90% identity with instant SEQ ID NO: 3:
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229
673
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Accordingly, the pending claims are understood to read upon repeats of prior art sequences, wherein the prior art explicitly teaches and discloses that such sequences may be fused and repeated to predictably and expectedly obtain “High affinity monoclonal antibody product binders”.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The claimed invention is the combination (or substitution) of prior art elements (e.g., SEQ ID NO: 35 of US’763) according to known methods of forming “High affinity monoclonal antibody product binders” comprising repeated binding domains as taught by US’576, to predictably and expectedly obtain a fusion protein consisting of repeats of SEQ ID NO: 35 of US’763 having high affinity for antibody products exactly as taught and suggested by the primary reference (see, e.g., MPEP § 2143(I)(A), (B), (D), (G)). Furthermore, each element would merely perform its art-recognized function in combination as it does separately.
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to make and synthesize a fusion protein containing repeats of a known prior art sequence.
Accordingly, claims 1-4 are rejected.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US6197927 teaches and discloses variants of Protein A, including SEQ ID NO: 35 (i.e., AVAQSFNMQCQRRFYEALHDPNLNEEQRNAKIKSIRDDC).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
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/RANDALL L BEANE/Primary Examiner, Art Unit 1654
1 “At least 3”, because more altered residues may be permissible depending upon the interpretation of “about”, which may imply substantially broader ranges.
2 E.g., instant SEQ ID NO: 3 is a 198-mer, and therefore sequences sharing 90% identity to it may have 19 positions altered to at least the 20 standard proteinogenic amino acids, which is 2019, or 5,242,880,000,000,000,000,000,000 species.