DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s response and amendments received June 23, 2026 are acknowledged.
Claims 10, 13, 17, 18, 21, 23-25, 27, and 30-33 have been canceled.
Claims 1-9, 11, 12, 14-16, 19, 28, and 29 have been amended.
Claims 1-9, 11, 12, 14-16, 19, 20, 22, 26, 28, and 29 are pending in the instant application.
Claims 11, 12, and 29 stand withdrawn from consideration as being drawn to a nonelected invention or species. See 37 CFR 1.142(b) and MPEP § 821.03, for reasons of record set forth in the Office Action mailed October 20, 2025.
Applicant is remined to their election without traverse of the invention of group I, drawn to polypeptides that bind alpha 1 antitrypsin, and the polypeptide species of SEQ ID NO:1 (AAHFHK) in the reply filed on December 19.
Claims 1-9, 14-16, 19, 20, 22, 26, and 28 are under examination in this office action as they read on the species of AAHFHK/SEQ ID NO:1.
Claim Objections
The objections to claims 7 and 8 have been withdrawn in view of the broadening amendments made to claims 7 and 8.
Claim Rejections - 35 USC § 112
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.
The rejection of claim 9 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form has been rendered moot by applicant’s claim amendments of June 23, 2026 which broaden the claim from which claim 9 depends.
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 1-8, 14-16, 19, 20, 22, 26, and 28 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.
Applicant has broadly claimed polypeptides which are minimally 6 amino acid residues in length which comprise the functional property of binding to alpha 1 antitrypsin (AAT). Specifically, as amended June 23, 2026, the claimed polypeptide must comprise an “alpha-1 antitrypsin peptide ligand” wherein the “peptide ligand” must be 6-8 residues in length even though the actual claimed polypeptide can be longer (as is made explicitly clear in for example instant claim 15). Independent claim 1 indicates a handful of residue types which must be present in the “alpha-1 antitrypsin ligand peptide”, such as histidine or lysine, but places no constrains on how such residues are arranged. Notably, as presently constructed claim 1 requires the minimal 6mer ligand peptide to have at least one residue from (i)-(iii) in any order, specifically (i) H or K, (ii) N or S, and (iii) F or W with the remaining residues being potentially anything. Dependent claims recite additional functional properties such as the characteristics of the binding epitopes within AAT (claim 4), how much AAT can be bound by the polypeptide (claims 5 and 6) or intended uses for such polypeptides such as purifying AAT from various liquid feedstocks (claims 19, 20, 22, and 26). Additionally, other dependent claims specify sequences of at least 6 amino acids by SEQ ID number that must be present in the claimed polypeptides (claims 7-9). To support such claims, applicant discloses working examples wherein the peptides of SEQ ID NOs:1-23 which are 6 or 8 residues in length were tested for binding to AAT, including when coupled to beads via a G or GSG linker sequence (see particularly Tables 3-6).
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by 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. See MPEP 2163. In The Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412) 19 F. 3d 1559, the court held that disclosure of a single member of a genus (rat insulin) did not provide adequate written support for the claimed genus (all mammalian insulins). In this same case, the court also noted: “A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. 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."). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.” The court has further stated that “Adequate written description requires a precise definition, such as by structure, formula, chemical name or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.” Id. at 1566, 43 USPQ2d at 1404 (quoting Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606). Also see Enzo-Biochem v. Gen-Probe 01-1230 (CAFC 2002). Recent court cases have emphasized the need for correlation between a well-defined structure and recited functional limitations. For example, the courts have indicated that recitation of an antibody which has specific functional properties in the absence of knowledge of the antibody sequences that give rise to said functional properties do not satisfy the requirements for written description. See for example AbbVie Deutschland GmbH v. Janssen Biotech. Inc. 759 F.3d 1285 (Fed. Cir. 2014) as well as Amgen v. Sanofi, (Fed Cir, 2017-1480. 10/5/2017). Applicant is reminded that the courts have long ruled that “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.” See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. As such, disclosure of a screening assay to test for functional properties of a polypeptide (such binding to AAT) does not provide evidence of possession of the polypeptide itself.
As discussed above, applicant made and tested 23 peptides for binding to AAT, either alone or via a G or GSG linker when conjugated to a solid support such as a resin bead. The claimed polypeptides are significantly broader in scope with most claims simply indicating that some particular amino acids amino acids should be present with no rhyme or reason as to how such residues are arranged within the longer claimed polypeptide structure. However, it is very well known that the sequence of a polypeptide (i.e. its structure) dictates its functional properties, and that even minor structural differences among structurally related compounds or compositions can result in substantially different biology, expression and activities. It is known in the art that many amino acid residues alter secondary structure, such as proline which often forms kinks in secondary structure, while residues like cysteine and methionine can be involved in disulfide bond formation (Stryer, see entire selection). Other residues can introduce either positive or negative charge to disrupt electrostatic interactions, or alter hydrophobicity or steric packing (ibid). Note that the minimum size of the claimed polypeptide is 6 residues, yet claim 1 indicates possible alternatives for only 3 of the positions and does not indicate where such residues occur within the larger peptide (for example claim 2 requires an alanine to be present, but it could be at position 1, 2, 3, 4, 5, 6, or somewhere else per the claim as six residues is the minimum size but no maximum size is recited). Further, Attwood (Science 2000; 290:471-473) teaches that “[i]t is presumptuous to make functional assignments merely on the basis of some degree of similarity between sequences (such as a given percent identity) while Skolnick et al. (Trends in Biotech., 18(1): 3439, 2000) teach that the skilled artisan is well aware that assigning functional activities for any particular protein or protein family based upon sequence homology is inaccurate, in part because of the multifunctional nature of proteins (e.g., "Abstract" and "Sequence based approaches to function prediction", page 34). Even in situations where there is some confidence of a similar overall structure between two proteins, only experimental research can confirm the artisan's best guess as to the function of the structurally related protein (see in particular "Abstract" and Box 2). Thus, in the absence of experimental data, artisans would not reasonably expect the vast genus of peptides encompassed by the independent claim and those dependent therefrom apart from claims 7-9 to have the functional property of binding AAT as there does not appear to be any conserved structure/sequence that when present in the peptide necessarily results in AAT binding activity that is set forth in the instant specification. It should also be pointed out that claims 7 and 8 recite percent identity mutations (i.e. at least 80%) and thus based upon the length of the SEQ ID numbers, one residue at random can be mutated relative to the reference SEQ ID number in question. Mutagenesis studies concerning the peptides of SEQ ID NOs:1-23, such as to say increase binding affinity, do not appear to have been performed.
Therefore, while artisans would reasonably accept that applicant was in possession of the polypeptides of SEQ ID NO:1-23 as well as extended versions of said polypeptides comprising G of GSG linker sequences, any or all of which may be present on a solid support such as a chromatography bead, artisans would not reasonably believe that applicant has in possession of the breath of incompletely defined polypeptide sequences which necessarily have the function of binding AAT. Logically, if applicant is not in possession of the full extent of the claimed polypeptides, applicant is also not in possession of products such as resins and other solid surfaces which comprise such polypeptides.
Applicant's arguments filed June 23, 2026 have been fully considered but they are not persuasive. Applicant argues on many grounds. Applicant begins by asserting that the 23 species disclosed by exact SEQ ID number (i.e. the peptides of SEQ ID NOs:1-23) are a representative number of species within the claimed genus. Applicant then asserts that functional properties, such as those recited in claim 4, are actual structural limitations. Indeed, applicant argues “These properties directly dictate the amino acid classes required for effective binding: cationic residues (H, K) for electrostatic complementarity; polar residues (N, S, E) for hydrogen bonding; and aromatic residues (F, W) for hydrophobic and π-stacking interactions. The amino acid type requirements in claim 1 are therefore not merely functional, they reflect a structurally grounded design rationale explicitly disclosed in the specification.” (see the paragraph bridging pages 10-11 of applicant’s response). Lastly, applicant argues the cited case law pertains to antibody-ligand interactions, that the claimed peptides are not antibodies, and therefore the legal concepts set forth in such decisions are immaterial to the issues at hand.
These arguments have been considered and are not persuasive. As set forth in the rejection of record, the breadth of the claims allows for the presence of many residues with in the sequences of the claimed polypeptides, such as cystine, proline, and methionine which were not recovered as part of applicant’s experiments (see most explicitly table 3 in working example 2). Thus, contrary to applicant’s assertions, the disclosed species are not representative of the diversity encompassed by the instant claims. It should be noted that while applicant has argued that three amino acid classes are needed for effective peptide binding namely cationic (H,K), polar (N,S,E), and aromatic (F, W), the elected species of SEQ ID NO:1, i.e. AAHFHK only comprises residues from the cationic and aromatic classes and thus it is clear that a representative from all three classes argued by applicant need not actually be present to give rise to binding function. Therefore, applicant’s assertions between the presence of particular groups of residues and functional properties is not persuasive as applicant’s own data and claims indicate that the structure asserted by applicant need not actually be present for binding activity to be observed, which indicates that the functional properties applicant as asserted as being structural properties are in actuality functional properties that need to be tested and validated via wet lab chemistry methodologies. With regard to case law, while applicant is correct that the claimed products are not antibodies, similar to antibodies they have a defined structure which give rise to the function of binding something else, in the instant case that something being alpha-1 antitrypsin. The rejection of record sets forth why the recited structural limitations are insufficient to necessarily give rise to the recited functional activities, and thus discussion of decisions concerning how much structure is needed to ensure a claimed product has the recited functional binding properties is, contrary to applicant’s assertions, highly relevant. The rejection is maintained.
Claim Rejections - 35 USC § 102
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 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.
The rejection of claims 1-3, 14, 16, 19, 20, 22, 26, and 28 under 35 U.S.C. 102(a)(1) as being anticipated by Grebe (WO 2012/038820) has been withdrawn in view of applicant’s claim amendments received June 23, 2026.
The rejection of claims 1-9, 14-16, 19, 20, 22, 26, and 28 under 35 U.S.C. 102(a)(1) as being anticipated by Chu et al. (J Chromatogr A, available online 22 July 2022) has been withdrawn in view of applicant’s remarks made of record as part of the June 23, 2026 response.
Specifically, on pages 12-13 of said response, applicant asserts that the grace period disclosure of Chu et al. does not qualify as prior art based upon 35 USC 102(b)(1)(A). Therefore, the rejection has been withdrawn.
The following are new grounds of rejection necessitated by applicant’s response and amendments received June 23, 2026.
Claims 1-9, 14, 16, 19, 20, 22, 26, and 28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Smith (WO 03/064469).
Smith et al. disclose a polypeptide which comprises a sequence which is 100% identical to instant SEQ ID NO:1.
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Such a polypeptide is further disclosed as being bound to a solid support such as a microtiter plate (see particularly pages 31-33).
Instant claim 1 recites “A peptide or polypeptide comprising an α-1 antitrypsin peptide ligand” and then proceeds to recite various amino acids which may or may not be present due to the liberal use of “and/or” phrasing, and recites that the peptide ligand “is from 6 amino acids to 8 amino acid in length”. Thus the claimed “peptide or polypeptide” must comprise an antitrypsin ligand that is 6-8 residues in length, even though the actual claimed peptide/polypeptide can be longer. This is because with regard to biological sequences, such as those identified by SEQ ID numbers, “comprising” or “open” language allows for, but does not require, additional, unrecited residues to be on either or both end of the recited sequence whereas “consisting of” or “closed” language dose not allow for anything more than which is explicitly recited, and it should be apparent that the closed/”consisting of” construct is always a member within the larger genus of open/”comprising” language. Indeed, as readily evidenced by instant claims 14 and 15 for example, the claimed peptide/polypeptide of claim 1 is not limited to being only 6-8 residues in length, but rather encompasses longer biological sequences in which the 6-8 residue “ligand peptide” is a subsequence within the larger whole. As shown in the alignment above, the polypeptide of Smith has a sequence 100% identical to instant SEQ ID NO:1, and this sequence of 100% identity is part of a longer polypeptide sequence. As such, the polypeptide of Smith comprises the 6 amino acid antitrypsin ligand binding peptide of SEQ ID NO:1 within a longer biological sequence.
It is noted that Smith do not discuss binding alpha-1 antitrypsin. However, as discussed above, the polypeptide disclosed by Smith meets the structural limitations set forth in claim 1, and due to the 100% identity with SEQ ID NO:1, the narrower structural limitations as set forth in claim 9 as well. As is clearly set forth in MPEP 2112, particularly 2112.01(II), "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id. Given that the same exact biological sequence is present when comparing the instant claims and the prior art, the functional properties recited in the instant claims, such as binding alpha 1 antitrypsin at a particular location or binding with some particular binding affinity or concentration, are necessarily present, even if undisclosed or unrecognized by Smith, because the structure is the same. See again MPEP 2112. Additionally, claims such as instant claim 19 recite intended uses for the claimed product, such a purifying alpha-1 antitrypsin from tissue culture media. Such statements of intended use provide patentable distinctiveness to a claimed product when they necessarily require a physical form or structure which is distinct from that disclosed in the prior art. See MPEP 2111.02. In the instant situation, there does not appear to be any structural reason why the products disclosed by Smith are unsuitable for the recited intended uses of claims 19, 20, 22, 26, and 28.
Therefore the prior art anticipated the instant claimed invention.
No claims are allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Michael Szperka whose telephone number is (571)272-2934. The examiner can normally be reached Monday-Friday 8:30-5:00.
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Michael Szperka
Primary Examiner
Art Unit 1641
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641
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