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 .
Applicant’s amendment filed on 1/22/2026 is acknowledged.
Claims 46, 114, 134, 138-139, 191-208 are pending.
Claims 1-45, 47-113, 115-133, 135-137, and 140-190 are cancelled.
The numbering of claims is not in accordance with 37 CFR 1.126 which requires the original numbering of the claims to be preserved throughout the prosecution. When claims are canceled, the remaining claims must not be renumbered. When new claims are presented, they must be numbered consecutively beginning with the number next following the highest numbered claims previously presented (whether entered or not).
There are two claim 193. Misnumbered claims 193-208 been renumbered 193-209. As such, claims 46, 114, 134, 138-139, 191-209 are pending and currently under consideration.
Information Disclosure Statement
The references disclosed in the IDS filed on 10/10/2023 and 1/22/2026 have been considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group I a fusion polypeptide that specifically binds the hIL-10R and the species encompassed by SEQ ID NO:125 in the reply filed on 1/22/2026 is acknowledged.
Claims 46, 114, 134, 138-139, 191-209 are under consideration as they read on the elected species of a fusion polypeptide comprising SEQ ID NO:125 that specifically binds the hIL-10R.
Claim Objections
Claims 467 objected to because of the following informalities:
Claims 46, 114, 138-139, and 191-195 recites, “..identical to the amino acid sequence of SED ID NO: 125”. The Examiner recommends the claim language to recite “… sequence identical to the full-length amino acid sequence of SEQ ID NO:125.”
Claim 207 recites, “The carrier of claim 200”. Claim 207’s claim dependency is incorrect. Correcting claim 207s claim dependency would obviate the objection.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 46, 114, 138-139, 191-195, and 208-209 rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more. The recitation of claim 46 reads on a naturally occurring protein as evidenced by the art of Davison et al. (PTO-892; page 1, Reference V; “Davison”) and Lockridge et al. (PTO-892; page 1, Reference U; “Lockridge”). Davison teaches the naturally occurring 185 amino acid viral interleukin-10 homolog expressed by primate cytomegalovirus which comprises instant SEQ ID NO:125 and an additional 26 amino acid signal sequence. The 26 amino acid signal sequence is “heterologous” to instant SEQ ID NO:125. Lockridge teaches a naturally occurring viral IL-10 homolog of which comprises a sequence which is 98.3% identical to instant SEQ ID NO:125 and an additional 26 amino acid signal sequence. The 26 amino acid signal sequence is “heterologous” to instant SEQ ID NO:125.
This polypeptide is not markedly different from the product’s naturally occurring counterpart conveying the same amino acid sequence information in its natural state even when comprised in a conjugate of claim 114, in a pharmaceutical composition of claim 138 and 208, and in a kit of claim 139 and 209. The recitation of a conjugate, a pharmaceutical composition, and a kit are merely assembling the product of nature together and does not add a meaningful limitation as it is merely a nominal or token extrasolution component of the claim, and is nothing more than an attempt to generally link the product of nature to a particular technological environment. The conjugate only comprises the heterologous protein and the pharmaceutical composition comprises a pharmaceutically acceptable excipient which reads on water.
This judicial exception is not integrated into a practical application because the claim is directed towards a. The discussion of the percent identity and conjugate is inherent in the naturally occurring protein. The only additional element in the claims is the excipient in the pharmaceutical composition.
As such, only claims 46, 114, 138-139, 191-195, and 208-209 are not patent eligible.
Claim Rejections - 35 USC § 112
Indefinite Language
Claims 46, 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 46 recites, “… wherein the polypeptide or protein is operably connected to a heterologous polypeptide or protein” and claim 114 recites, “… wherein the polypeptide or protein is operably connected to a heterologous moiety”. The term “heterologous polypeptide or protein” and “heterologous moiety” are unclear because the reference protein is not defined thus it is unclear how to determine what is or is not “heterologous” sequence. The broadest reasonable interpretation reads on any amino acid sequence which is in addition to and/or not in SEQ ID NO:125. Given the recitation of percent identity language, it follows that the “heterologous” sequence could be a fragment unrelated to SEQ ID NO:125 which is located within a protein which is 85% sequence identical to SEQ ID NO:125. Additionally, the fullest scope of the terms encompasses a limitless genus of proteins and a limitless genus of moieties which could be proteins, RNA, nucleic acids, etc. based solely on being “heterologous” without specifying any particular sequence, structure, or function, thus failing to provide objective boundaries of the claimed invention. Read in light of the specification, the terms “heterologous polypeptide or protein” and ‘heterologous moiety” do not provide sufficient guidance, as it could plausibly cover millions of unrelated proteins, RNA, and DNA sequences.
The term “any one or more of the foregoing” recited in claim 139 is indefinite as only one isolated polypeptide or protein comprising an amino acid sequence at least 85%-100% identical to SEQ ID NO:125 that specifically binds to hIL-10R is claimed to be a component of the claimed kit. It is unclear as to whether there are more than one essential components to the claimed kit. The Examiner recommends reciting the specific components intended to be included in the claimed kit to obviate the rejection.
Claim 207 recites the limitation "the carrier of claim 200" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Enablement
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 46, 114, 134, 138-139, and 191-209 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
While being enabled for:
a fusion polypeptide or protein comprising an isolated polypeptide or protein comprising an amino acid sequence 100% sequence identical to the full length of amino acid sequence of SEQ ID NO:125 that specifically binds the hIL-10R operably connected to a heterologous polypeptide or protein wherein the amino acid sequence of the heterologous polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:16-21 or 27-34; AND an isolated polypeptide or protein comprising an amino acid sequence 100% sequence identical to the full length of SEQ ID NO:125 that specifically binds the hIL-10R operably connected to a heterologous moiety.
the specification does not reasonably provide enablement for:
a fusion polypeptide or protein comprising an isolated polypeptide of protein comprising an amino acid sequence 85-99% sequence identical to the full length of amino acid sequence of SEQ ID NO:125 that specifically binds the hIL-10R operably connected to a heterologous polypeptide or protein wherein the amino acid sequence of the heterologous polypeptide comprises or consists of the amino acid sequence of any one of SEQ ID NOs:16-21 or 27-34, comprising no more than 1-, or 10 amino acid variations; AND an isolated polypeptide or protein comprising an amino acid sequence 85-99% sequence identical to the full length of SEQ ID NO:125 that specifically binds the hIL-10R operably connected to a heterologous moiety.
The breadth of claims 46, 191-194, 204, 206-209 encompass all fusion polypeptide or proteins comprising an isolated polypeptide or protein comprising all amino acid sequences 85%-100% identical to the full-length amino acid sequence SEQ ID NO:125 with any amino acid variations operably connected to a heterologous polypeptide that comprises or consists of SEQ ID NOs:16-21 or 27-34 with any amino acid variations (1 up to 10). The breadth of claims 114, 134, and 138-139 encompass all isolated polypeptide or protein comprising all amino acid sequence 85%-100% identical to the full-length amino acid sequence SEQ ID NO:125 with any amino acid variations.
Regarding the fusion protein comprising an isolated protein comprising 85-100% sequence identity SEQ ID NO:125 that specifically binds hIL-10, the specification discloses that the identified immunomodulatory proteins and polypeptides that bind hIL-10R exhibit one or more improved properties over hIL-10 such as increasing binding affinity for the hIL-10R, increased potency, enhanced suppression of one ore more pro-inflammatory cytokines, etc. (page 30, [00128]). The specification defines a functional variant as a polypeptide that comprises at least one but no more than 15%, not more than 12%, not more than 10%, no more than 8% amino acid variation compared to the amino acid sequence of a reference polypeptide, wherein the polypeptide retains at least one particular function of the reference polypeptide. For example, a functional variant of hIL-10 polypeptide can refer to a hIL-10 protein comprising one or more amino acid substitutions as compared to a reference hIL-10 protein (e.g. wild type) that retains the ability to specifically bind the hIL-10R (page 36, [00155]).
Additionally, the specification discloses SEQ ID NO:125 to be a preferred embodiment of the fusion protein where it may engage hIL-10R with a higher potency than hIL-10 (page 103, [00256]). Furthermore, Example 1 of the specification discloses (page 271, [00575]) 175 IMPs identified as having the ability to bind hIL-10R wherein SEQ ID NO:125 is labeled as IMP-7 without signal peptide (see Table 2). A set of 97 immunomodulatory fusion proteins (IFPs) were generated wherein a fragment of IFP-7 (SEQ ID NO:64) is 100% sequence identical to the full-length IMP-7 (SEQ ID NO:125) wherein IMP-7 is operably connected to hIL-2 signal sequence, and an effector function reduced hIgG4 Fc region, a peptide linker (page 271, [00575]). Example 3 discloses IFP-7 being able to engage hIL-10R with higher potency than hIL-10 even in the presence of the anti-hIL-10Ralpha antibody (page 273, [00578]; page 275, [00580]). Examples 4-8 disclose IFP-7 showing greater inhibition of pro-inflammatory cytokine expression compared to reference hIL-10 Fc fusion protein and was more potent than dexamethasone alone in suppressing IFNγ, TNFα, and IL-17a expression in vivo and in vitro (page 276, [00584]; page 278, [00590]) and in vivo treatment with dexamethasone and IFP-7 resulted in significantly increased human immune cell engraftment vs the untreated and human Fc controls and mice treated with dexamethasone and IFP-7 exhibited longer survival than control mice (page 279, [00592]).
However, the specification does not sufficiently disclose an isolated polypeptide or protein comprising an amino acid sequence 85%-99% sequence identical to SEQ ID NO:125 that specifically binds the hIL-10R. The specification does not disclose within SEQ ID NO:125, what amino acid residues are required for specifically binding IL-10 and what specific amino acids and the number of amino acid residues are required in order to preserve the function of specifically binding hIL-10R.
Regarding the heterologous polypeptide or protein comprising or consisting of any one of SEQ ID NOs:16-21 or 27-34, the specification (page 115, [00281]; Table 4; page 126, [2297]) discloses the heterologous polypeptide or protein to comprise or consist of a human hIgG1 or hIgG4 Fc region which comprises or consists of at least a portion or a human hIgG1 or hIgG4 hinge region, a CH2 region, and a CH3 region wherein the hIgG1 or hIgG4 Fc region comprises 1 or more but less than 15% amino acid substitutions that affects Fc effector function relative to a reference (e.g.) wildtype Ig Fc region.
It is well established in the art that it is highly unpredictable which changes in amino acid sequence can be made in binding structures such that the derived polypeptide retains the ability to bind. Sailer et al. (PTO-892; page 1, Reference W) teaches that “"proteins exist as ensembles of similar conformations. The effect of a mutation depends on the relative probabilities of conformations in the ensemble, which in turn, depend on the exact amino acid sequence of the protein. Accumulating substitutions alter the relative probabilities of conformations, thereby changing the effects of future mutations. This manifests itself as subtle but pervasive high-order epistasis. Uncertainty in the effect of each mutation accumulates and undermines prediction. Because conformational ensembles are an inevitable feature of proteins, this is likely universal" (Sailer; abstract, whole document); and that "a key point from our work is that unpredictability can arise even in this extraordinary simple system. The problem of predicting evolution will only become harder as the complexity and realism of the models increase. Using a larger protein, for example, would increase the number of possible options and degeneracy of trajectories, making predictions more challenging." (Sailer; page 11942, left column, whole document).
One of ordinary skill in the art could not predict which amino acids within the full-length amino acid sequences of the recited genus of fusion polypeptides could be substituted for which amino acids and whether the resulting polypeptide combinations exhibits binding. Predicting polypeptide structure from sequence data of a single amino acid sequence and attempting to utilize the predicted structural determinations to ascertain binding or functional aspects of any protein and what changes can be tolerated with respect thereto is complex and well outside the realm of routine experimentation. In re Fisher indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
As such the claims are not enabled for the genus of fusion polypeptides or proteins and isolated polypeptides proteins comprising an amino acid sequence at least 85-99% sequence identical to SEQ ID NO:125 operably connected to a heterologous polypeptide comprising or consisting of any one of SEQ ID NOs:16-21 or 27-34, comprising no more than 1-, or 10 amino acid variations recited in the claims for predictable function to specifically bind hIL-10R. One of ordinary skill in the art cannot use fusion polypeptides with unpredictable functions. One of ordinary skill in the art would be required to practice undue experimentation to practice the invention commensurate in scope with the claims.
In view of the quantity of experimentation necessary, the lack of working examples, the unpredictability in the art, the lack of sufficient guidance in the specification, and the breadth of the claims, it would take undue trials and errors to make and use the encompassed fusion polypeptides or proteins and isolated polypeptides or proteins comprising an amino acid sequence at least 85%-99% sequence identical to SEQ ID NO:125 operably connected to a heterologous polypeptide comprising or consisting of any one of SEQ ID NOs:16-21 or 27-34, comprising no more than 1-, or 10 amino acid variations recited in the claims for predictable function to specifically bind hIL-10R.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
Written Description
Claims 46, 114, 9 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 is in possession of: a fusion protein comprising an isolated polypeptide comprising an amino acid sequence 100% sequence identical to the full-length amino acid sequence SEQ ID NO: 125 that specifically binds the hIL-10R wherein the polypeptide is operably connected to a heterologous polypeptide comprising amino acid sequence 100% sequence identical of any one of the full length SEQ ID NOs:16-21 or 27-34 AND a conjugate comprising an isolated polypeptide comprising an amino acid sequence 100% identical to the amino acid sequence SEQ ID NO:125.
Applicant is not in possession of: the fusion protein comprising an isolated polypeptide comprising an amino acid sequence 85%-99% identical to the amino acid sequence SEQ ID NO: 125 that specifically binds the hIL-10R and wherein the polypeptide is operably connected to a heterologous polypeptide wherein the heterologous polypeptide comprises a half-life extension polypeptide; AND a conjugate comprising an isolated polypeptide comprising an amino acid sequence 85%-99% identical to the amino acid sequence SEQ ID NO: 125 that specifically binds the hIL-10R and wherein the polypeptide is operably connected to a heterologous moiety.
The claims encompass all fusion polypeptides or proteins comprising an isolated polypeptide comprising any amino acid sequence 85-100% identical to SEQ ID NO:125 wherein the polypeptide is operably connected to any heterologous polypeptide including any half-life extension polypeptide. Additionally, the claims encompass a fusion polypeptide with no more than 1,- or 10 amino acid variations throughout the entire polypeptide. The claims also encompass all conjugate comprising an isolated polypeptide comprising any amino acid sequence 85-100% identical to SEQ ID NO:125 wherein the polypeptide is operably connected to any heterologous moiety.
The skilled artisan cannot envision all the fusion polypeptides and conjugates possibilities recited in the instant claims.
The specification (page 104, [00256]) discloses the amino acid sequence of the immunomodulatory protein or polypeptide to consist of an amino acid sequence at least 85%-100% identical to the amino acid sequence of SEQ ID NO:125 which may be preferred as it engages hIL-10R with a high potency than hIL-10. The specification discloses the heterologous polypeptide or protein to comprise the amino acid sequence of any one of SEQ ID NOs:16-21 or 27-34 wherein some embodiments consist of a heterologous polypeptide comprising or consisting of 1 or more but less than 15% (less than 12%, less than 10%, less than 8%) amino acid variations as outlined in Tables 5, 10, and 11 (page 120, [00285]). In some embodiments, the variations can decrease one or more Fc effector function relative to reference that does not comprise the modification including ADCC, ADCP, CDC, and binding affinity to one or more human Fc receptor (page 126, [00297]). The specification additionally discloses in Examples 1-8, an immunomodulatory fusion protein named IFP-7 which contains 100% of the full-length amino acid sequence of SEQ ID NO:125 operably connected to a to hIL-2 signal sequence, and an effector function reduced hIgG4 Fc region, a peptide linker (page 271, [00575]). In vivo and in vitro, IFP-7 engages hIL-10R with higher potency than hIL-10 (page 273, [00578]) even in the presence of the anti-hIL-10Ralpha antibody (page 275, [00580]) and IFP-7 shows greater inhibition of pro-inflammatory cytokine expression compared to reference hIL-10 Fc fusion protein and was more potent than dexamethasone alone in suppressing IFNγ, TNFα, and IL-17a expression (page 276, [00584]; page 278, [00590]) and in vivo treatment with dexamethasone and IFP-7 resulted in significantly increased human immune cell engraftment vs the untreated and human Fc controls and mice treated with dexamethasone and IFP-7 exhibited longer survival than control mice (page 279, [00592]).
The specification does not provide adequate written description of the claimed invention. The legal standard for sufficiency of a patient’s (or a specification’s) written description “reasonably conveys to the artisan that the inventor has possession at that time of the … claimed subject matter”, Vas-Cath, Inc. V. Mahurkar, 19 U.S.P.Q.2d 1111 (Fed. Cir. 1991). In the instant case, the specification does not confer to the artisan that the applicant had possession at the time of invention of the claimed invention.
However, absent a limiting species variant of isolated polypeptides or proteins comprising SEQ ID NO:125 and heterologous polypeptides or proteins comprising any one of SEQ ID NOs:16-21 or 27-34, the genus opens up the claimed invention to encompass all species variants of the fusion polypeptides or proteins and all species variants of the isolated polypeptides or proteins operably connected to all species variants of heterologous moieties. The art of Sailer et al. (PTO-892; page 1, Reference W) teaches that "proteins exist as ensembles of similar conformations. The effect of a mutation depends on the relative probabilities of conformations in the ensemble, which in turn, depend on the exact amino acid sequence of the protein. Accumulating substitutions alter the relative probabilities of conformations, thereby changing the effects of future mutations. This manifests itself as subtle but pervasive high-order epistasis. Uncertainty in the effect of each mutation accumulates and undermines prediction. Because conformational ensembles are an inevitable feature of proteins, this is likely universal" (Sailer; abstract; whole document); and that "a key point from our work is that unpredictability can arise even in this extraordinary simple system. The problem of predicting evolution will only become harder as the complexity and realism of the models increase. Using a larger protein, for example, would increase the number of possible options and degeneracy of trajectories, making predictions more challenging." (Sailer; page 11942, left column, whole document).
As such, there is insufficient written description of the required kind of structure identifying information about the corresponding makeup of the claimed fusion polypeptides to demonstrate possession.
The specification discloses the term “heterologous” to describe a first element in reference to a second element means that the first element and second element do not exist in nature disposed as described. In one embodiment, the heterologous polypeptide is a polypeptide derived from a polypeptide or protein other than a polypeptide or protein comprising or consisting of the amino acid sequence of any one of SEQ ID NOS: 108-454. For example, a non-limiting example of a heterologous polypeptide, as described herein, is a human lg Fc region (page 36-37, [00161]). The heterologous polypeptide can also comprise an antibody comprising one or more Ig heavy chain constant regions (e.g. a CH2 region, a CH3 region, a hinge region, an Fc region) wherein the Ig is an IgG more specifically an IgG1, IgG2, IgG3, or IgG4 (page 113, [00275]-[00276]). The heterologous polypeptide or protein can comprise any one of the amino acid sequences in Tables 4 and 10 (e.g. SEQ ID NOs: 12-34, 455-470, and 531-543) and can comprise no more than 1,- or 10 amino acid substitutions as shown in Tables 5 and 11 (SEQ ID NOs: 35-48 and 471-478).
The specification discloses the term “heterologous moiety” to include, but not limited to proteins, peptides, small molecules, nucleic acids, carbohydrates, lipids, and synthetic polymers and could be a detectable moiety or a half-life extension moiety. For example, a polypeptide comprising a "heterologous moiety" means a polypeptide that is joined to a moiety (e.g., small molecule, polypeptide, polynucleotide, carbohydrate, lipid, synthetic polymer (e.g., polymers of PEG), etc.) that is not joined to the polypeptide in nature. In one embodiment, the heterologous moiety is not derived from a polypeptide or protein comprising or consisting of the amino acid sequence of any one of SEQ ID NOS: 108-454. For example, a non-limiting example of a heterologous moiety is a heterologous polypeptide (as defined herein).
The specification discloses “a half-life extension polypeptide or protein” to refer to a polypeptide or protein that when operably connected to another polypeptide or protein (the subject polypeptide or protein), increases the half-life of the subject polypeptide or protein in vivo when administered to a subject (e.g., a human subject). The pharmacokinetic properties of the polypeptide or protein can be evaluated utilizing in vivo models known in the art (page 36, [00160]).
However, the specification does not sufficiently disclose the genus of terms “heterologous polypeptide or protein”, “half-life extension polypeptide or protein”, or “heterologous moiety” encompass nor disclose what specific amino acid residues are required for a protein to be considered a heterologous polypeptide or heterologous moiety or a half-life extension polypeptide; the number of unaltered amino acid residues required for a protein to be defined as a heterologous protein; and the relationship between the isolated polypeptide and heterologous polypeptide or moiety and half-life extension polypeptide so that the function of the isolated polypeptide remains unchanged. Additionally, there is no way of knowing what exists in nature, so the heterologous protein or moiety could be a fragment unrelated to SEQ ID NO:125 which is located within a protein which is 85% sequence identical to SEQ ID NO:125.
Absent a limiting definition of the term “heterologous polypeptide” and “heterologous moiety” and “half-life extension polypeptide”, the term opens up the claimed invention to encompass all proteins, all moieties, and all half-life extension polypeptides.
The art of Schmidt et al (PTO-892; page 2, Reference V) teaches fusion proteins can be sorted into primarily three different categories: T1/2 (half life), targeting (or binding), or toxicity (cell killing) (Schmidt; Chapter 1.2; Figure 1.2). Schmidt teaches that although there are several advantages with fusion proteins, there are a number of significant challenges including fusion partners having incompatible properties causing aggregation or misfolding or one domain while the conditions might be perfect for the other domain; conflicting stability requirements; difficulty controlling and tuning relative amounts of each component thus complicating dosing for optimal efficacy and safety; high potential for immunogenicity (Schmidt; Chapter 1.2). Schmidt teaches that fusion proteins must be well designed in order to enhance the function of the fusion protein. (Schmidt; Chapter 1.2).
The art of Aboutalebi (PTO-892; page 1, Reference X) teaches a variety of strategies to enhance half-life in drug delivery systems including Albumin related tags, Fc domain, transferrin, ADC and bsAbs, glycsolyaltion, HESylation, HEPylation, polysiation, ELP, XTEN, PASylation, HAPylation, CTP, and PEG (Aboutalebi; Figure 1). Aboutalebi teaches that each method has its own advantages and disadvantages and choosing the best half-life extension polypeptide or protein depends on desired size of the resulting fusion protein, side effects, and disease subtype (Aboutalebi; page 2, paragraphs 1-2).
The art of Schmidt et al (PTO-892; page 2, Reference V) teaches fusion proteins can be sorted into primarily three different categories: T1/2 (half life), targeting (or binding), or toxicity (cell killing) (Schmidt; Chapter 1.2; Figure 1.2). Schmidt teaches that although there are several advantages with fusion proteins, there are a number of significant challenges including fusion partners having incompatible properties causing aggregation or misfolding or one domain while the conditions might be perfect for the other domain; conflicting stability requirements; difficulty controlling and tuning relative amounts of each component thus complicating dosing for optimal efficacy and safety; high potential for immunogenicity (Schmidt; Chapter 1.2). Schmidt teaches that fusion proteins must be well designed in order to enhance the function of the fusion protein. (Schmidt; Chapter 1.2).
The art of Czajkowsky et al (PTO-892; page 2, Reference U) teaches Fc-based fusion proteins are composed of an immunoglobulin Fc domain that is directly linked to another peptide which could be a ligand, a peptidic antigen, or a ‘bait’ protein (Czajkowsky; Page 1, Paragraph 1). Czajkowsky teaches that while modifications to the Fc-domain can generally improve therapeutic function, subtle binding properties of the fused partner make a dominating contribution to the ultimate activity of the Fc fusion protein in the clinical setting (Czajkowsky; Page 5, paragraph 2). Czajkowsky further teaches that etanercept (Fc-fusion drug) and infliximab (intact mAb) both naturalize soluble tumor necrosis factor (TNF)-alpha but only infliximab was only able to induce a clinical response in Crohn’s patients since infliximab only was able to bind activated lymphocytes, induce apoptosis, and activate caspase-3 since there were differences in the affinity and stoichiometry of the drugs for transmembrane TNF-alpha (Czajkowsky; Page 5, paragraph 2). As a result, the Fc fusion protein can alter binding affinity to the peptide’s target.
As such, claims 46, 114, 134, 138-139, and 191-209 do not meet the requirements of 35 U.S.C. 112(a) for written description as they are currently written.
Priority
This application claims domestic priority to U.S. Provisional Application 63/394,155 filed on 8/1/2022, U.S. Provisional Application 63/483,419 filed on 2/6/2023, and U.S. Provisional Application 63/502,864 filed on 5/17/2023.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 46, 114, 138-139, 191-193, and 208-209 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lockridge et al (PTO-892; page 1, Reference U; "Lockridge").
Lockridge teaches the discovery of a viral homolog of IL-10 identified in rhesus cytomegalovirus (RhCMV) (Lockridge; Abstract; page 1, right column, paragraph 2). Lockridge teaches the isolation of the RhCMV IL-10 sequence from the RhCMV genome wherein the RhCMV IL-10 ORF was 189 amino acids (Lockridge, page 273, left column, paragraph 2; right column, paragraph 1). The length of the cleaved The CMV IL-10-like ORF when aligned with cIL-10 revealed 20 amino acids conserved, including 4 cysteine residues along with an additional 15 amino acids conserved in all four CMV representatives (The reference CMV-IL-10-like ORF is 98.2% sequence identical between reference amino acids 27-185 to instant SEQ ID NO: 125; see UniProt sequence alignment attached) (Lockridge; page 275, left column, paragraph 1):
Lockridge further teaches that sera from a rhesus macaque chronically infected with RhCMV recognized the viral IL-10-like protein and that an immune response was detected 2 weeks post inoculation with a continued response with increased reactivity at 6 months inoculation indicating the IL-10-like protein was expressed during RhCMV infection and was recognized by the host immune system (Lockridge; page 275, right column, paragraph 2). Lockridge teaches the IL-10-like gene to be compatible with the known functions of cIL-10 such as decreasing antigen-specific CD4+ T cell proliferation by reducing the expression of MHC II molecules on antigen-presenting cells (Lockridge; page 277, right column, paragraph 2).
Regarding claim 46, Lockridge teaches a fusion polypeptide or protein comprising an isolate polypeptide or protein comprising an amino acid sequence at least 85%,- or 100% identical to the amino acid sequence of SEQ ID NO: 125 that specifically binds the human IL-10 Receptor (hIL-10R), and wherein the polypeptide or protein is operably connected to a heterologous polypeptide or protein (Lockridge; see ABSS sequence alignment above; Instant SEQ ID NO:125 98.3% is identical to reference amino acids 27-185 wherein amino acids 1-26 are the heterologous protein operably connected to the isolated polypeptide).
Regarding claim 114, Lockridge teaches a conjugate comprising an isolated polypeptide or protein comprising an amino acid sequence at least 85%,- or 100% identical to the amino acid sequence of SEQ ID NO: 125 that specifically binds the human IL-10 Receptor (hIL-l0R), and wherein the polypeptide or protein is operably connected to a heterologous moiety (Lockridge; see ABSS sequence alignment above; Instant SEQ ID NO:125 is 98.3% identical to reference amino acids 27-185 wherein amino acids 1-26 are the heterologous protein operably connected to the isolated polypeptide).
Regarding claim 138, Lockridge teaches a pharmaceutical composition comprising an isolated polypeptide or protein comprising an amino acid sequence at least 85%,- or 100% identical to the amino acid sequence of SEQ ID NO: 125 that specifically binds the human IL-10 Receptor (hIL-l0R); and a pharmaceutically acceptable excipient (Lockridge; page 275, right column, paragraph 2; see ABSS sequence alignment above; Instant SEQ ID NO:125 is 98.3% identical to reference amino acids 27-185 wherein amino acids 1-26 are the heterologous protein operably connected to the isolated polypeptide).
Regarding claim 139, Lockridge teaches a kit comprising an isolated polypeptide or protein comprising an amino acid sequence at least 85%,- or 100% identical to the amino acid sequence of SEQ ID NO: 125 that specifically binds the human IL-10 Receptor (hIL-10R); and optionally instructions for using any one or more of the foregoing (Lockridge; page 278 [the kit contains no other components]; see ABSS sequence alignment above; Instant SEQ ID NO:125 is 98.3% identical to reference amino acids 27-185 wherein amino acids 1-26 are the heterologous protein operably connected to the isolated polypeptide).
Regarding claim 191, Lockridge teaches the fusion protein or polypeptide of claim 46, wherein the amino acid sequence of the isolated polypeptide or protein comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 125 (Lockridge; see ABSS sequence alignment above; Instant SEQ ID NO:125 is 98.3% identical to reference amino acids 27-185 wherein amino acids 1-26 are the heterologous protein operably connected to the isolated polypeptide).
Regarding claim 192, Lockridge teaches the fusion protein or polypeptide of claim 46, wherein the amino acid sequence of the isolated polypeptide or protein comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 125(Lockridge; see ABSS sequence alignment above; Instant SEQ ID NO:125 is 98.3% identical to reference amino acids 27-185 wherein amino acids 1-26 are the heterologous protein operably connected to the isolated polypeptide).
Regarding claim 193, Lockridge teaches the fusion protein or polypeptide of claim 46, wherein the amino acid sequence of the isolated polypeptide or protein comprises an amino acid sequence at least 97% identical to the amino acid sequence of SEQ ID NO: 125. (Lockridge; see ABSS sequence alignment above; Instant SEQ ID NO:125 is 98.3% identical to reference amino acids 27-185 wherein amino acids 1-26 are the heterologous protein operably connected to the isolated polypeptide).
Regarding claim 208, Lockridge teaches a pharmaceutical composition comprising the fusion polypeptide or protein of claim 46; and a pharmaceutically acceptable excipient (Lockridge; page 275, right column, paragraph 2; see ABSS sequence alignment above; Instant SEQ ID NO:125 is 98.3% identical to reference amino acids 27-185 wherein amino acids 1-26 are the heterologous protein operably connected to the isolated polypeptide).
Regarding claim 209, Lockridge teaches a kit comprising the fusion polypeptide or protein of claim 46 (Lockridge; page 278 [the kit contains no other components]; see ABSS sequence alignment above; Instant SEQ ID NO:125 is 98.3% identical to reference amino acids 27-185 wherein amino acids 1-26 are the heterologous protein operably connected to the isolated polypeptide).
The reference teachings anticipate the claimed invention.
Claims 46, 114, 139, 191-195, and 209 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Davison et al (PTO-892; page 1, Reference V; "Davison").
Davison teaches a viral interleukin-10 (IL-10) homolog encoded by simian cytomegalovirus where it plays a role in regulating host immune response (see attached UniProt sequence alignment; The reference viral IL-10 homolog is 100% identical to instant SEQ ID NO:125 between reference amino acids 27-185; reference amino acids 1-26 represent the heterologous polypeptide sequence operably connected to instant SEQ ID NO:125).
Regarding claim 46, Davison teaches a fusion polypeptide or protein comprising an isolate polypeptide or protein comprising an amino acid sequence at least 85%,- or 100% identical to the amino acid sequence of SEQ ID NO: 125 that specifically binds the human IL-10 Receptor (hIL-10R), and wherein the polypeptide or protein is operably connected to a heterologous polypeptide or protein (Davison; see ABSS sequence alignment above; Instant SEQ ID NO:125 100% is sequence identical to reference amino acids 27-185 wherein amino acids 1-26 are the heterologous protein operably connected to the isolated polypeptide).
Regarding claim 114, Davison teaches a conjugate comprising an isolated polypeptide or protein comprising an amino acid sequence at least 85%,- or 100% identical to the amino acid sequence of SEQ ID NO: 125 that specifically binds the human IL-10 Receptor (hIL-l0R), and wherein the polypeptide or protein is operably connected to a heterologous moiety (Davison; see ABSS sequence alignment above; Instant SEQ ID NO:125 is 100% identical to reference amino acids 27-185 wherein amino acids 1-26 are the heterologous protein operably connected to the isolated polypeptide).
Regarding claim 139, Davison teaches a kit comprising an isolated polypeptide or protein comprising an amino acid sequence at least 85%,- or 100% identical to the amino acid sequence of SEQ ID NO: 125 that specifically binds the human IL-10 Receptor (hIL-10R); and optionally instructions for using any one or more of the foregoing (Davison; page 17, Figure I.1.9 [the kit contains no other components]; see ABSS sequence alignment above; Instant SEQ ID NO:125 is 100% identical to reference amino acids 27-185 wherein amino acids 1-26 are the heterologous protein operably connected to the isolated polypeptide).
Regarding claim 191, Davison teaches the fusion protein or polypeptide of claim 46, wherein the amino acid sequence of the isolated polypeptide or protein comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO: 125 (Davison; see ABSS sequence alignment above; Instant SEQ ID NO:125 is 100% identical to reference amino acids 27-185 wherein amino acids 1-26 are the heterologous protein operably connected to the isolated polypeptide).
Regarding claim 192, Davison teaches the fusion protein or polypeptide of claim 46, wherein the amino acid sequence of the isolated polypeptide or protein comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 125 (Davison; see ABSS sequence alignment above; Instant SEQ ID NO:125 is 100% identical to reference amino acids 27-185 wherein amino acids 1-26 are the heterologous protein operably connected to the isolated polypeptide).
Regarding claim 193, Davison teaches the fusion protein or polypeptide of claim 46, wherein the amino acid sequence of the isolated polypeptide or protein comprises an amino acid sequence at least 97% identical to the amino acid sequence of SEQ ID NO: 125. (Davison; see ABSS sequence alignment above; Instant SEQ ID NO:125 is 100% identical to reference amino acids 27-185 wherein amino acids 1-26 are the heterologous protein operably connected to the isolated polypeptide).
Regarding claim 194, Davison teaches the fusion protein or polypeptide of claim 46, wherein the amino acid sequence of the isolated polypeptide or protein comprises an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO: 125. (Davison; see ABSS sequence alignment above; Instant SEQ ID NO:125 is 100% identical to reference amino acids 27-185 wherein amino acids 1-26 are the heterologous protein operably connected to the isolated polypeptide).
Regarding claim 195, Davison teaches the fusion protein or polypeptide of claim 46, wherein the amino acid sequence of the isolated polypeptide or protein comprises an amino acid sequence at least 100% identical to the amino acid sequence of SEQ ID NO: 125. (Davison; see ABSS sequence alignment above; Instant SEQ ID NO:125 is 100% identical to reference amino acids 27-185 wherein amino acids 1-26 are the heterologous protein operably connected to the isolated polypeptide).
Regarding claim 209, Davison teaches a kit comprising the fusion polypeptide or protein of claim 46 (Davison; page 17, Figure I.1.9 [the kit contains no other components]; see ABSS sequence alignment above; Instant SEQ ID NO:125 is 100% identical to reference amino acids 27-185 wherein amino acids 1-26 are the heterologous protein operably connected to the isolated polypeptide).
The reference teachings anticipate the claimed invention.
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.
Claims 46, 138, 196-205, and 208 are rejected under 35 U.S.C. 103 as being unpatentable over Lockridge (PTO-892; page 1, Reference U) in view of US 20250367255 A1 (PTO-892; page 1, Reference B; "Lin”) and of US 9187552 B2 (PTO-892; page 1, Reference E, “Stadheim”) and US 8557769 B2 (PTO-892; page 1, Reference D, “Coskun”).
Lockridge teaches the discovery of a viral homolog of IL-10 identified in rhesus cytomegalovirus (RhCMV) (Lockridge; Abstract; page 1, right column, paragraph 2). Lockridge teaches the isolation of the RhCMV IL-10 sequence from the RhCMV genome wherein the RhCMV IL-10 ORF was 189 amino acids (Lockridge, page 273, left column, paragraph 2; right column, paragraph 1). The length of the cleaved The CMV IL-10-like ORF when aligned with cIL-10 revealed 20 amino acids conserved, including 4 cysteine residues along with an additional 15 amino acids conserved in all four CMV representatives (The reference CMV-IL-10-like ORF is 98.2% sequence identical between reference amino acids 27-185 to instant SEQ ID NO: 125; see UniProt sequence alignment attached) (Lockridge; page 275, left column, paragraph 1):
Lockridge further teaches that sera from a rhesus macaque chronically infected with RhCMV recognized the viral IL-10-like protein and that an immune response was detected 2 weeks post inoculation with a continued response with increased reactivity at 6 months inoculation indicating the IL-10-like protein was expressed during RhCMV infection and was recognized by the host immune system (Lockridge; page 275, right column, paragraph 2). Lockridge teaches the IL-10-like gene to be compatible with the known functions of cIL-10 such as decreasing antigen-specific CD4+ T cell proliferation by reducing the expression of MHC II molecules on antigen-presenting cells (Lockridge; page 277, right column, paragraph 2).
Lockridge does not teach instant claims 196-205 wherein the heterologous fusion polypeptide comprises a half-life extension polypeptide or protein; wherein the heterologous polypeptide comprises an immunoglobulin (Ig) Fc region; wherein the Ig Fc region comprises a portion of a hinge region, CH2 region, and a CH3 region; wherein the Ig Fc region comprises a hinge region, a CH2 region, and a CH3 region; wherein the Ig Fc region is a human Ig (hIg) Fc region; wherein the hIg is a human IgG; wherein the hIg is a hIgG is hIgG1 or hIgG4; wherein the amino acid sequence of the heterologous polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:16-21 or 27-34; wherein the amino acid sequence of the heterologous polypeptide comprises or consists of the amino acid sequence of any one of SEQ ID NOs:16-21 or 27-34, comprising no more than 1-,or 10 amino acid variations; wherein the Ig Fc region comprises one or more amino acid substitutions relative to a reference Ig Fc region that reduces or abolishes one or more of the following effector functions relative to the reference Fc region: ADCC, CDC, and/or affinity to one or more Fc receptor.
However, Lin does teach a CD47 blocking agent comprising a form of human SIRPalpha that binds CD47, and incorporate a region of its extracellular domain linked with a particularly useful form of an IgG1-based Fc region or an IgG4-based Fc region wherein the SIRPalpha protein is fused directly or indirectly with an antibody constant region, of Fc region, having at least some effector function (i.e. SIRPalpha is an Fc fusion) (Lin; [0003]; [0068]). The Fc component “having an effector function” is an Fc component having at least some contribution for instance to antibody-dependent cellular cytotoxicity (ADCC) or some ability to fix complement (Lin; [0068]). Lin teaches the preferred embodiment of the instant invention wherein the Fc region is based on human antibodies of the IgG1 or IgG4 isotope which also includes the hinge-CH2-CH3 domains (Lin; [0068]; [0072]). Lin teaches the IgG1 constant region has the amino acid sequence as shown in reference SEQ ID NO:2 (Reference SEQ ID NO:2 comprises 100% of instant SEQ ID NO:16 between reference amino acids 9-227; comprises 100% of instant SEQ ID NO:17 between reference amino acids 8-226; comprises 100% of instant SEQ ID NO:18 between reference amino acids 5-227; and comprises 100% of instant SEQ ID NO:19 between reference amino acids 5-226) (Lin; [0069]). Lin additionally teaches the IgG4 constant region has the amino acid sequence as shown in reference SEQ ID NO:6 (Reference SEQ ID NO:6 is 100% sequence identical to instant SEQ ID NOs:31-32; Reference SEQ ID NO:6 comprises 100% of instant SEQ ID NO:27 between reference amino acids 13-229; comprises 100% of instant SEQ ID NO:28 between reference amino acids 13-228; comprises 100% of instant SEQ ID NO:29 between reference amino acids 7-229; comprises 100% of instant SEQ ID NO: 30 between reference amino acids 7-228) (Lin; [0072]). Lin teaches the Fc region to incorporate 1-, or 10 amino acid alterations including alterations that affect certain Fc properties such as Fc dimer stability, glycosylation, and half-life extension while retaining Fc receptor binding (Lin; [0073]). Lin also teaches the agent being provided in a dosage form comprising a pharmaceutically acceptable carrier one or more of water, saline, phosphate buffered saline, dextrose, glycerol, ethanol and the like, as well as combinations thereof so that the agent can be effectively administered to a patient (Lin; [0097]).
Stadheim teaches Fc containing polypeptides which are useful as human and animal therapeutic agents (Stadheim; page 37, column 1, lines 5-9). Stadheim teaches the variable region of a monoclonal antibody recruits effecter cells such as natural killer (NK) cells and NK cells bind to the constant region (Fc) of the antibody and destroy cells to which the antibody is bound which is known as antibody-dependent cell cytotoxicity (ADCC) (Stadheim; page 37, column 1, lines 22-25). Stadheim teaches ADCC depends on N-glycosylation of the Fc region and structures that lack N-glycosylation still bind antigens but do not mediate ADCC (Stadheim; page 376, column 1, lines 25-34). Stadheim teaches that modification of specific amino acids in the Fc region of an antibody to modify the effector function is desirable (Stadheim; page 37, column 1, lines 47-50). Furthermore, Stadheim teaches the Fc region of an antibody to comprise reference SEQ ID NO:19 (Reference SEQ ID NO:19 is 100% sequence identical to instant SEQ ID NOs:20-21) (Stadheim; page 38, column 4, lines 34-36).
Coskun teaches a GLP-1 fusion protein containing an Fc portion which is derived from human IgG4 but comprises one or more substitutions compared to the wild-type sequence as shown in SEQ ID NO:5 (Reference SEQ ID NO:5 is 100% sequence identical to instant SEQ ID NOs:33-34) (Cuskon; page 2-3, column 2-3, lines 66 and 1-2). Coskun teaches the Fc portion can include the hinge region and extend through the CH2 and CH3 domains and can further include one or more glycosylation sites (Cuskon; page 3, column 4, lines 19-22).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date, to have modified the fusion polypeptide containing IL-10-like ORF of Lockridge with the human Ig Fc constant region with half-life enhancing alterations of Lin with reasonable expectation of success.
One of ordinary skill in the art would have been motivated to combine the fusion polypeptide containing IL-10-like ORF of Lockridge with the human Ig Fc constant region with half-life enhancing alterations of Lin to increase the fusion protein’s duration.
Therefore, it would have been obvious to one of ordinary skill in the art to combine the fusion polypeptide containing the IL-10-like ORF of Lockridge with the human Ig Fc constant region with half-life enhancing alterations of Lin to yield predictable results of extending the fusion protein’s duration within a target specimen.
It would have been prima facie obvious to one of ordinary skill, in the art before the effective filing date, to have modified the fusion polypeptide containing IL-10-like ORF of Lockridge with the human IgG1 or IgG4 Fc constant regions as shown in reference SEQ ID NOs: 2 and 6 of Lin with the Fc constant regions as shown in reference SEQ ID NO:19 of Stadheim with the Fc constant regions as shown in reference SEQ ID NO:5 of Cuskon with reasonable expectation of success.
One of ordinary skill in the art would have been motivated to operably connect the IL-10-like ORF of Lockridge with a heterologous polypeptide containing a human IgG1 or IgG4 Fc constant region of Lin, Stadheim, and Cuskon to recruit effecter immune cells such as NK cells to destroy and kill a cell expressing hIL-10R.
Therefore, it would have been obvious to a person of ordinary skill in the art to
combine the fusion polypeptide containing the IL-10-like ORF of Lockridge with the IgG1 or IgG4 Fc constant regions of Lin, Stadheim, and Cuskon to yield a fusion protein that specifically binds hIL-10R to induce an effective immune response against a cell expressing hIL-10R.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date, to have modified the fusion polypeptide containing IL-10-like ORF of Lockridge with the human IgG1 or IgG4 Fc constant regions with one or no more than 10 amino acid variations of Lin, Stadheim, and Cuskon with reasonable expectation of success.
One of ordinary skill in the art would have been motivated to combine the fusion polypeptide containing the IL-10-like ORF of Lockridge with the IgG1 or IgG4 human Fc regions with one or no more than ten amino acid variations of Lin, Stadheim, and Cuskon in order to modify ADCC, Fc dimer stability, glycosylation, and half-life extension while retaining Fc receptor binding.
Therefore, it would have been obvious to a person of ordinary skill in the art to combine the fusion polypeptide containing the IL-10-like ORF of Lockridge with the IgG1 or IgG4 Fc constant regions with one to no more than ten amino acid variations of Lin, Stadheim, and Cuskon to yield predictable results of altered ADCC and enhance destruction and killing of the target cell.
The invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence on the contrary.
Claims 46, 134, and 206-207 are rejected under 35 U.S.C. 103 as being unpatentable over Lockridge as applied to claim 46 above, and further in view of US 10272050 B2 (PTO-892; Page 1, Reference A; "Farokhzad").
Lockridge has been discussed above. Lockridge does not teach a carrier comprising the isolated polypeptide comprising an amino acid sequence at least 85%-100% identical to SEQ ID NO:125 of instant claim 134 and a carrier comprising the fusion polypeptide or protein of claim 46 wherein the carrier is a lipid nanoparticle of instant claims 206-207.
Farokhzad does teach compositions and methods of using lipid nanoparticles as carriers for therapeutic agents (Farokhzad; Abstract; [2]). Farokhzad teaches that nanotechnology provides a means of improved methods for delivery of biomolecules with nanoparticles being effective platforms for protein delivery due to the possibility of fine-tuning their biophysiochemical properties and their ability to protect and release proteins in a controlled manner (Farokhzad; [2]). Farokhzad teaches that nanoparticles allow for the efficient delivery of labile biomolecules using an organic-solvent-free polymer thermoexpansion mechanism with clinical potential, capable of effectively delivering a molecule such as IL-10 in a sustained manner with minimal or no loss of bioactivity, and an improved half-life and in vivo efficacy compared with administration of the therapeutic agent alone (Farokhzad; [3]). Farokhzad also teaches the nanoparticles to delivery organic molecules such as Fc fusion proteins that can offer stability or selective targeting of a cell or tissue type (Farokhzad; [65]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date, to combine the fusion polypeptide of Lockridge with the lipid nanoparticle carrier of Farokhzad with reasonable expectation of success.
One of ordinary skill in the art would have been motivated to combine the fusion polypeptide of Lockridge with the lipid nanoparticle carrier of Farokhzad in order to improve the half-life and in vivo efficacy of the fusion protein with minimal to no loss of bioactivity.
Therefore, it would have been obvious to a person of ordinary skill in the art to combine the fusion polypeptide Lockridge with the lipid nanoparticle carrier of Farokhzad to yield predictable results of improving the half-life and in vivo efficacy of the fusion protein with minimal to no loss of bioactivity.
The invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence on the contrary.
Claims 46, 134, and 206-207 are rejected under 35 U.S.C. 103 as being unpatentable over Davison et al (PTO-892; page 1, Reference V; "Davison") in view of US 10272050 B2 (PTO-892; page 1, Reference A; "Farokhzad").
Davison teaches a viral interleukin-10 (IL-10) homolog encoded by simian cytomegalovirus where it plays a role in regulating host immune response (see attached UniProt sequence alignment; The reference viral IL-10 homolog is 100% identical to instant SEQ ID NO:125 between reference amino acids 27-185; reference amino acids 1-26 represent the heterologous polypeptide sequence operably connected to instant SEQ ID NO:125).
Davison does not teach a carrier comprising an isolated polypeptide or protein comprising an amino acid sequence at least 85-100% sequence identical to the amino acid sequence of SEQ ID NO:125 that specifically binds the hIL-10R of instant claim 134; and a carrier comprising the isolated polypeptide or protein of claim 46 wherein the carrier is a lipid nanoparticle of instant claims 206-207.
Farokhzad does teach compositions and methods of using lipid nanoparticles as carriers for therapeutic agents (Farokhzad; Abstract; [2]). Farokhzad teaches that nanotechnology provides a means of improved methods for delivery of biomolecules with nanoparticles being effective platforms for protein delivery due to the possibility of fine-tuning their biophysiochemical properties and their ability to protect and release proteins in a controlled manner (Farokhzad; [2]). Farokhzad teaches that nanoparticles allow for the efficient delivery of labile biomolecules using an organic-solvent-free polymer thermoexpansion mechanism with clinical potential, capable of effectively delivering a molecule such as IL-10 in a sustained manner with minimal or no loss of bioactivity, and an improved half-life and in vivo efficacy compared with administration of the therapeutic agent alone (Farokhzad; [3]). Farokhzad also teaches the nanoparticles to delivery organic molecules such as Fc fusion proteins that can offer stability or selective targeting of a cell or tissue type (Farokhzad; [65]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date, to combine the fusion polypeptide of Davison with the lipid nanoparticle carrier of Farokhzad with reasonable expectation of success.
One of ordinary skill in the art would have been motivated to combine the fusion polypeptide of Davison with the lipid nanoparticle carrier of Farokhzad in order to improve the half-life and in vivo efficacy of the fusion protein with minimal to no loss of bioactivity.
Therefore, it would have been obvious to a person of ordinary skill in the art to combine the fusion polypeptide Davison with the lipid nanoparticle carrier of Farokhzad to yield predictable results of improving the half-life and in vivo efficacy of the fusion protein with minimal to no loss of bioactivity.
Claims 46, 138, and 208 are rejected under 35 U.S.C. 103 as being unpatentable over Davison et al (PTO-892; page 1, Reference V; "Davison") in view of US 20250367255 A1 (PTO-892; page 1, Reference B; "Lin”).
Davison is discussed above. Davison does not teach a pharmaceutical composition comprising the fusion polypeptide or protein comprising an isolated polypeptide of protein comprising an amino acid sequence at least 85-100% sequence identical to the amino acid sequence of SEQ ID NO:125 that specifically binds IL-10R; and a pharmaceutically acceptable excipient of instant claim 138; and a pharmaceutical composition comprising the fusion polypeptide or protein of claim 46; and a pharmaceutically acceptable excipient of instant claim 208.
However, Lin does teach a CD47 blocking agent comprising a form of human SIRPalpha that binds CD47, and incorporate a region of its extracellular domain linked with a particularly useful form of an IgG1-based Fc region or an IgG4-based Fc region wherein the SIRPalpha protein is fused directly or indirectly with an antibody constant region, of Fc region, having at least some effector function (i.e. SIRPalpha is an Fc fusion) (Lin; [0003]; [0068]). The Fc component “having an effector function” is an Fc component having at least some contribution for instance to antibody-dependent cellular cytotoxicity (ADCC) or some ability to fix complement (Lin; [0068]). Lin also teaches the agent being provided in a dosage form comprising a pharmaceutically acceptable carrier one or more of water, saline, phosphate buffered saline, dextrose, glycerol, ethanol and the like, as well as combinations thereof so that the agent can be effectively administered to a patient (Lin; [0097]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date, to have modified the fusion polypeptide of Davison with the pharmaceutically acceptable carrier of Lin with reasonable expectation of success.
One of ordinary skill in the art would have been motivated to combine the fusion polypeptide of Davison with the pharmaceutically acceptable carrier of Lin to effectively administer the fusion polypeptide to a patient in need.
Therefore, it would have been obvious to one of ordinary skill in the art to combine the fusion polypeptide of Davison with the pharmaceutically acceptable carrier of Lin to effectively administer the fusion polypeptide and treat a patient in need.
The invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence on the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 46, 114, 134, 138-139, 191-195, 206, and 208-209 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 120, 259, 264, 269, 272, 282, 287, and 289-290 of copending Application No. 19/267,934 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because ‘934 teaches in reference claim 1 a fusion protein comprising any two or more of (a) a protein comprising an amino acid sequence at least about 85%-100% identical to the amino acid sequence set forth in any one of SEQ ID NOs:34-386 (Reference SEQ ID NO: 40 is 100% identical to instant SEQ ID NO:125 between reference amino acids 27-185; Reference SEQ ID NO:165 is 98.1% identical to instant SEQ ID NO:125 between reference amino acids 27-185; Reference SEQ ID NO:218 is 100% sequence identical to instant SEQ ID NO:125; Reference SEQ ID NO:340 is 98.1% sequence identical to instant SEQ ID NO:125); (b) a protein comprising an amino acid sequence of at least 85%-100% identical to amino acid sequence set forth in any one of SEQ ID NOs:387-576; a conjugate comprising the fusion protein of reference claim 1 operably connected to a heterologous moiety; a carrier comprising the fusion protein of claim 1; a pharmaceutical composition comprising the fusion protein of claim 1; a kit comprising the fusion protein of claim 1 and optionally instructions for using any one of more of the foregoing. ‘934 further teaches in reference claim 120 a fusion protein comprising (a) integrin binding domain; and one or more of (b) a protein comprising an amino acid sequence at least about 85%-100% identical to the amino acid sequence set forth in any one of SEQ ID NOs:34-576 (Reference SEQ ID NO: 40 is 100% identical to instant SEQ ID NO:125 between reference amino acids 27-185; Reference SEQ ID NO:165 is 98.1% identical to instant SEQ ID NO:125 between reference amino acids 27-185; Reference SEQ ID NO:218 is 100% sequence identical to instant SEQ ID NO:125; Reference SEQ ID NO:340 is 98.1% sequence identical to instant SEQ ID NO:125); a conjugate comprising the fusion protein of claim 120 operably connected to a heterologous moiety; a carrier comprising the fusion protein of claim 120; a pharmaceutical composition comprising the fusion protein of claim 120; a kit comprising the fusion protein and optionally instructions for using any one or more of the foregoing of claim 120.
Therefore, ‘934 anticipate instant claims 46, 114, 134, 138, 139, 191-195, 206, 208-209. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 46, and 196-205 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 120 of copending Application No. 19/267,934 in view of US 20250367255 A1 (PTO-892; page 1, Reference B; "Lin”) in further view of US 9187552 B2 (PTO-892; page 1, Reference E, “Stadheim”) in further view of US 8557769 B2 (PTO-892; page 1, Reference D, “Coskun”).
‘934 teaches in reference claim 1 a fusion protein comprising a fusion protein comprising any two or more of (a) a protein comprising an amino acid sequence at least about 85%-100% identical to the amino acid sequence set forth in any one of SEQ ID NOs:34-386 (Reference SEQ ID NO: 40 is 100% identical to instant SEQ ID NO:125 between reference amino acids 27-185; Reference SEQ ID NO:165 is 98.1% identical to instant SEQ ID NO:125 between reference amino acids 27-185; Reference SEQ ID NO:218 is 100% sequence identical to instant SEQ ID NO:125; Reference SEQ ID NO:340 is 98.1% sequence identical to instant SEQ ID NO:125); (b) a protein comprising an amino acid sequence of at least 85%-100% identical to amino acid sequence set forth in any one of SEQ ID NOs:387-576.
However, ‘934 does not teach instant claims the second heterologous protein to further comprise a half-life extension polypeptide; an immunoglobulin (Ig) Fc region; wherein the Ig Fc region comprises at least a portion of a hinge domain, a CH2 domain, and a CH3 domain; wherein the Ig Fc region comprises a hinge domain, a CH2 domain, and a CH3 domain; wherein the Ig Fc region is a human IgG (hIgG); wherein the hIgG is hIgG1 or hIgG4; wherein the amino acid sequence of the heterologous polypeptide comprises the amino acid sequence of any one of SEQ ID NOs:16-21 or 27-34; wherein the amino acid sequence of the heterologous polypeptide comprises or consists of the amino acid sequence of any one of SEQ ID NOs: 16-21 or 27-34, comprising no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid variations; wherein the lg Fc region comprises one or more amino acid substitutions relative to a reference lg Fc region that reduces or abolishes one or more of the following effector functions relative to the reference Fc region: antibody dependent cell mediated cytotoxicity (ADCC), complement dependent cytotoxicity (CDC), and/or affinity to one or more Fc receptor.
However, Lin teaches a CD47 blocking agent comprising a form of human SIRPalpha that binds CD47, and incorporate a region of its extracellular domain linked with a particularly useful form of an IgG1-based Fc region or an IgG4-based Fc region wherein the SIRPalpha protein is fused directly or indirectly with an antibody constant region, of Fc region, having at least some effector function (i.e. SIRPalpha is an Fc fusion) (Lin; [0003]; [0068]). The Fc component “having an effector function” is an Fc component having at least some contribution for instance to antibody-dependent cellular cytotoxicity (ADCC) or some ability to fix complement (Lin; [0068]). Lin teaches the preferred embodiment of the instant invention wherein the Fc region is based on human antibodies of the IgG1 or IgG4 isotope which also includes the hinge-CH2-CH3 domains (Lin; [0068]; [0072]). Lin teaches the IgG1 constant region has the amino acid sequence as shown in reference SEQ ID NO:2 (Reference SEQ ID NO:2 comprises 100% of instant SEQ ID NO:16 between reference amino acids 9-227; comprises 100% of instant SEQ ID NO:17 between reference amino acids 8-226; comprises 100% of instant SEQ ID NO:18 between reference amino acids 5-227; and comprises 100% of instant SEQ ID NO:19 between reference amino acids 5-226) (Lin; [0069]). Lin additionally teaches the IgG4 constant region has the amino acid sequence as shown in reference SEQ ID NO:6 (Reference SEQ ID NO:6 is 100% sequence identical to instant SEQ ID NOs:31-32; Reference SEQ ID NO:6 comprises 100% of instant SEQ ID NO:27 between reference amino acids 13-229; comprises 100% of instant SEQ ID NO:28 between reference amino acids 13-228; comprises 100% of instant SEQ ID NO:29 between reference amino acids 7-229; comprises 100% of instant SEQ ID NO: 30 between reference amino acids 7-228) (Lin; [0072]). Lin teaches the Fc region to incorporate 1-, or 10 amino acid alterations including alterations that affect certain Fc properties such as Fc dimer stability, glycosylation, and half-life extension while retaining Fc receptor binding (Lin; [0073]).
Stadheim teaches Fc containing polypeptides which are useful as human and animal therapeutic agents (Stadheim; page 37, column 1, lines 5-9). Stadheim teaches the variable region of a monoclonal antibody recruits effecter cells such as natural killer (NK) cells and NK cells bind to the constant region (Fc) of the antibody and destroy cells to which the antibody is bound which is known as antibody-dependent cell cytotoxicity (ADCC) (Stadheim; page 37, column 1, lines 22-25). Stadheim teaches ADCC depends on N-glycosylation of the Fc region and structures that lack N-glycosylation still bind antigens but do not mediate ADCC (Stadheim; page 376, column 1, lines 25-34). Stadheim teaches that modification of specific amino acids in the Fc region of an antibody to modify the effector function is desirable (Stadheim; page 37, column 1, lines 47-50). Furthermore, Stadheim teaches the Fc region of an antibody to comprise reference SEQ ID NO:19 (Reference SEQ ID NO:19 is 100% sequence identical to instant SEQ ID NOs:20-21) (Stadheim; page 38, column 4, lines 34-36).
Coskun teaches a GLP-1 fusion protein containing an Fc portion which is derived from human IgG4 but comprises one or more substitutions compared to the wild-type sequence as shown in SEQ ID NO:5 (Reference SEQ ID NO:5 is 100% sequence identical to instant SEQ ID NOs:33-34) (Cuskon; page 2-3, column 2-3, lines 66 and 1-2). Coskun teaches the Fc portion can include the hinge region and extend through the CH2 and CH3 domains and can further include one or more glycosylation sites (Cuskon, page 3, column 4, lines 19-22).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date, to have modified the fusion polypeptide containing SEQ ID NO: 40, 165, 218, or 340 operably connected to a second protein of ‘934 with the human Ig Fc constant region with half-life enhancing alterations of Lin with reasonable expectation of success.
One of ordinary skill in the art would have been motivated to swap the second protein of ‘934 with human Ig Fc constant region with half-life enhancing alterations of Lin to increase the fusion protein’s duration.
Therefore, it would have been obvious to one of ordinary skill in the art to combine the fusion polypeptide containing SEQ ID NO: 40, 165, 218, or 340 operably connected to a second protein of ‘934 with the human Ig Fc constant region with half-life enhancing alterations of Lin to yield predictable results of extending the fusion protein’s duration within a target specimen.
It would have been prima facie obvious to one of ordinary skill, in the art before the effective filing date, to have modified fusion polypeptide containing SEQ ID NO: 40, 165, 218, or 340 operably connected to a second protein of ‘934 with the human IgG1 or IgG4 Fc constant regions as shown in reference SEQ ID NOs: 2 and 6 of Lin with the Fc constant regions as shown in reference SEQ ID NO:19 of Stadheim with the Fc constant regions as shown in reference SEQ ID NO:5 of Cuskon with reasonable expectation of success.
One of ordinary skill in the art would have been motivated to operably connect the fusion polypeptide containing SEQ ID NO: 40, 165, 218, or 340 of ‘934 with a heterologous polypeptide containing a human IgG1 or IgG4 Fc constant region of Lin, Stadheim, and Cuskon to recruit effecter immune cells such as NK cells to destroy and kill a cell expressing hIL-10R.
Therefore, it would have been obvious to a person of ordinary skill in the art to
combine the fusion polypeptide containing SEQ ID NO: 40, 165, 218, or 340 of ‘934 with the IgG1 or IgG4 Fc constant regions of Lin, Stadheim, or Cuskon to yield a fusion protein that specifically binds hIL-10R to induce an effective immune response against a cell expressing hIL-10R.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date, to have combine the fusion polypeptide containing SEQ ID NO: 40, 165, 218, or 340 of ‘934 with the human IgG1 or IgG4 Fc constant regions with one or no more than 10 amino acid variations of Lin, Stadheim, and Cuskon with reasonable expectation of success.
One of ordinary skill in the art would have been motivated to combine the fusion polypeptide containing the fusion polypeptide containing SEQ ID NO: 40, 165, 218, or 340 of ‘934 with the IgG1 or IgG4 human Fc regions with one or no more than ten amino acid variations of Lin, Stadheim, and Cuskon in order to modify ADCC, Fc dimer stability, glycosylation, and half-life extension while retaining Fc receptor binding.
Therefore, it would have been obvious to a person of ordinary skill in the art to combine the fusion polypeptide containing the fusion polypeptide containing SEQ ID NO: 40, 165, 218, or 340 of ‘934 with the IgG1 or IgG4 Fc constant regions with one to no more than ten amino acid variations of Lin, Stadheim, and Cuskon to yield predictable results of altered ADCC and enhance destruction and killing of the target cell.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence on the contrary.
This is a provisional nonstatutory double patenting rejection.
Claims 46, 134, and 206-207 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 120, 264, and 287 of copending Application No. 19/267,934 in view of US 10272050 B2 (PTO-892; page 1, Reference A; "Farokhzad").
'934 has been discussed above. The claimed invention differs from '934 with respect to instant claims 134 and 206-207, wherein a carrier comprises the isolated an isolated polypeptide comprising an amino acid sequence at least 85%-100% identical to SEQ ID NO:125 and wherein a carrier comprises the fusion protein of claim 46 wherein the carrier is a lipid nanoparticle. However, Farokhzad does teach compositions and methods of using lipid nanoparticles as carriers for therapeutic agents (Farokhzad; Abstract; [2]). Farokhzad teaches that nanotechnology provides a means of improved methods for delivery of biomolecules with nanoparticles being effective platforms for protein delivery due to the possibility of fine-tuning their biophysiochemical properties and their ability to protect and release proteins in a controlled manner (Farokhzad; [2]). Farokhzad teaches that nanoparticles allow for the efficient delivery of labile biomolecules using an organic-solvent-free polymer thermoexpansion mechanism with clinical potential, capable of effectively delivering a molecule such as IL-10 in a sustained manner with minimal or no loss of bioactivity, and an improved half-life and in vivo efficacy compared with administration of the therapeutic agent alone (Farokhzad; [3]). Farokhzad also teaches the nanoparticles to delivery organic molecules such as Fc fusion proteins that can offer stability or selective targeting of a cell or tissue type (Farokhzad; [65]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date, to combine the fusion polypeptide of ‘934 with the lipid nanoparticle carrier of Farokhzad with reasonable expectation of success.
One of ordinary skill in the art would have been motivated to combine the fusion polypeptide of ‘934 with the lipid nanoparticle carrier of Farokhzad in order to improve the half-life and in vivo efficacy of the fusion protein with minimal to no loss of bioactivity.
Therefore, it would have been obvious to a person of ordinary skill in the art to combine the fusion polypeptide ‘934 with the lipid nanoparticle carrier of Farokhzad to yield predictable results of improving the route of administration of the fusion polypeptide and improve the half-life and in vivo efficacy of the fusion protein with minimal to no loss of bioactivity.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence on the contrary.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LEAH ELIZABETH STEIN whose telephone number is (571)272-0093. The examiner can normally be reached M-F 8-5:30 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at (571) 272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LEAH ELIZABETH STEIN/Examiner, Art Unit 1641
/NORA M ROONEY/Primary Examiner, Art Unit 1641