DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-20 are pending. Claims 1, 3-4, 9-11, 14, 16, and 18-19 were amended in the Reply filed 3/26/2026. Claims 18-19 are directed to a non-elected invention (methods), and claims 1-16 and 20 are drawn to non-elected species. Accordingly, claims 1-16 and 18-20 are withdrawn. Claim 17 is presently considered.
Election/Restrictions
Applicant’s election without traverse of Group I (original claims 1-17 and 20) and the species of SEQ ID NO: 1 in Example 1 in the reply filed on 10/27/2025 is acknowledged.
Example 1 with SEQ ID NO: 1 is disclosed as
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(see, e.g., Spec. filed 10/19/2022 at ¶[0111] at page 23 at Table 1). Therefore, the originally elected species is understood as follows, Example 1 (see, e.g., Spec. filed 10/19/2022 at p. 23) is understood to mean 20 mg/g of SEQ ID NO: 1, 5 mg/g of Polysorbate 80, and “adequate amount” of “sodium citrate hydrate solution” buffer1 with a pH of 3.0, an “adequate amount” of Sodium hydroxide (potentially 0 mg/ml was “adequate”), and a final pH of 3.0 (see, e.g., Spec. filed 10/19/2022 at Table 1 at ¶[0111]), wherein SEQ ID NO: 1 has the following sequence:
MGKGDPKKPRGKMSSYAFFVQTCREEHKKKHPDASVNFSEFSKK
The term “adequate amount” is not defined or clarified on record, and therefore an “adequate amount” is understood to be potentially 0 mg/ml or more, wherein 0 mg/ml may be “adequate”.
Accordingly, Example 1 is understood to be an aqueous composition comprising SEQ ID NO: 1, polysorbate 80, citrate buffer solution (citric acid hydrate and sodium citrate hydrate in aqueous solution), water, and sodium hydroxide.
The claims that did and did not read upon the originally elected species were discussed in the previous actions, and those discussions are incorporated herein (see, e.g., Action mailed 1/02/2026 at 3-4 at bridging ¶). However, it is the Examiner’s understanding that Applicant is alleging that the originally elected species differs from the limitations of instant claim 1, and that claims 1 and 17 are not obvious variants of each other (see discussion in section entitled “Response to Applicant Arguments”, below). In view of Applicant’s response, the originally elected species has been reviewed and it is understood to read only upon instant claim 17, because claim 17 is the only claim that requires the claimed product to explicitly include and require distilled water in the claimed product. Accordingly, claims 1-4 and 11-13 should have been withdrawn in the Action mailed 1/02/2026, as directed to a non-elected species, because “when the pharmaceutical composition is dissolved in distilled water” (see instant claim 1) is a contingent limitation presumes the recited composition as claimed lacks water; this interpretation is reasonable because claim 17 is presumed to satisfy 35 USC §112(d), and differs from the scope of claim 1 by the addition of water. Claims 1-4 and 11-13 are now withdrawn as directed to non-aqueous compositions. This change does not impact examination, because the originally elected species was fully examined, and examination did not proceed beyond the originally elected species, which reads upon claim 17.
The originally elected species was previously examined on record and found obvious. The amended claims are understood to continue reading upon aqueous formulations. Following extensive search and examination, the originally elected species was previously deemed obvious in view of the prior art as applied below. Per MPEP § 803.02(III)(A),
Following election, the Markush claim will be examined fully with respect to the elected species and further to the extent necessary to determine patentability. Note that where a claim reads on multiple species, only one species needs to be taught or suggested by the prior art in order for the claim to be anticipated or rendered obvious...
If the Markush claim is not allowable, the provisional election will be given effect and examination will be limited to the Markush claim and claims to the elected species, with claims drawn to species patentably distinct from the elected species held withdrawn from further consideration.
Accordingly, the elected species was previously deemed obvious. The originally elected species has been searched and considered again, but has again deemed obvious in view of the art of record.
Claims 18-19 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/27/2025.
Claims 1-16 and 20 are withdrawn2 from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species (i.e., non-aqueous formulations), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/27/2025.
Claim 17 is presently considered.
Priority
The priority claim to JP2020-074929 (filed 4/20/2020) and PCT/JP2021/015792 (filed 4/19/2021) are each acknowledged.
Examiner notes that no certified translation of the Foreign Application JP2020-074929 (filed 4/20/2020) has been placed on record. If applicant wants the application to be accorded benefit of the non-English language application, a certified translation is required (see 35 U.S.C. 119(b)(3), 37 CFR 1.55(g)(1)-(4)). Applicant is advised that any showing of priority that relies on a non-English language application is prima facie insufficient if no certified translation of the application is on file. See 37 CFR 41.154(b).
Information Disclosure Statement
The IDS filed 4/21/2026 is acknowledged and presently considered.
Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Claim 17, which incorporates the limitations of claim 1, is representative of the pending claim scope, and is understood to be directed to aqueous, injectable pharmaceutical compositions made by a product-by-process limitation (i.e., “dissolving a pharmaceutical composition according to claim 1 in distilled water for injection”3; see also originally elected Example 14). The applicable claim interpretation is discussed below.
“Pharmaceutical composition” is understood to be a liquid, aqueous, injectable pharmaceutical formulation, as present in the originally elected species.
Examiner notes that claim 1 recites the clause “wherein the pH is 3.0 to 4.5 when the pharmaceutical composition is dissolved in distilled water for injection”, wherein the word “when” combined with the active method step “is dissolved in” is understood to be a contingent limitation, that indicates that water is not currently present in the claimed invention. Per MPEP § 2111.04(II), a contingent limitation within a product claim acts as a functional limitation because the claimed product “requires structure for performing the function should the condition occur” (see, e.g., § 2111.04(II)). Upon review of the originally elected species and Applicant’s arguments pertaining to claim interpretation5, claim 1 is understood to be limited to non-elected species, namely a non-aqueous composition (e.g., powder, granules, solid, etc.); this interpretation is reasonable in view of claim 15 and Applicant’s arguments distinguishing the scope of claim 1 from aqueous compositions6. However, the non-elected, non-aqueous formulation of claim 1 is relevant to the scope of claim 17, because the aqueous composition recited at claim 17 is understood to have a pH of 3.0 to 4.5 as recited at claim 1.
Originally elected Example 1, with SEQ ID NO: 1, is understood to be
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(see, e.g., Spec. filed 10/19/2022 at ¶[0111] at page 23 at Table 1). Therefore, the originally elected species is understood as follows, Example 1 (see, e.g., Spec. filed 10/19/2022 at p. 23) is understood to mean 20 mg/g of SEQ ID NO: 1, 5 mg/g of Polysorbate 80, and “adequate amount” of “sodium citrate hydrate solution” buffer7 with a pH of 3.0, an “adequate amount” of Sodium hydroxide (potentially 0 mg/ml was “adequate”), and a final pH of 3.0 (see, e.g., Spec. filed 10/19/2022 at Table 1 at ¶[0111]), wherein SEQ ID NO: 1 has the following sequence:
MGKGDPKKPRGKMSSYAFFVQTCREEHKKKHPDASVNFSEFSKK
The term “adequate amount” is not defined or clarified on record, and therefore an “adequate amount” is understood to be potentially 0 mg/ml or more, wherein 0 mg/ml may be “adequate”.
Accordingly, Example 1 is understood to be an aqueous composition comprising SEQ ID NO: 1, polysorbate 80, citrate buffer solution (citric acid hydrate and sodium citrate hydrate in aqueous solution), water, and sodium hydroxide.
Additional claim interpretations are set forth below.
Withdrawn Claim Rejections
The rejection of claims 1-4, 11-13, and 17 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in view of the amendments filed 3/26/2026, including amendments deleting claims 1(b) and 1(c), and amended claim 11.
The rejection of claims 1-4, 11-13, and 17 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 is withdrawn in view of the amendments filed 3/26/2026, including amendments deleting claims 1(b) and 1(c), and amended claim 11.
All rejections previously applied to claims 1-4 and 11-13 are withdrawn to the extent the rejections read upon non-elected species that do not fall within the scope of claim 17 or are otherwise not obvious variants of claim 17, as examination has not been extended beyond the originally elected species of aqueous, injectable formulations. These revisions have not altered the citations relied upon by the Examiner or the rationales supporting a conclusion of obviousness.
Revised Claim Rejections as Necessitated by Applicant Arguments and Amendments
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over US2015/0274792A1 (Oct. 1, 2015) and Nuijen et al8.
Claim interpretation: The applicable claim interpretation is set forth above in a separate section, and in preceding rejections. Those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claim 17 and a pharmaceutical composition comprising SEQ ID NO: 1, US’792 teaches, claims, and discloses all possible pharmaceutical compositions comprising SEQ ID NO: 5, which shares 100% sequence identity with instant SEQ ID NO: 1 (compare US’792 at claims 1-6, SEQ ID NO: 5, ¶[0062] with instant claim 1 and SEQ ID NO: 1), wherein the pharmaceutical formulation may be “formulated according to the usual methods” (see, e.g., US’792 at ¶¶[0063]) and comprise various concentrations and pharmaceutical additives including surfactants, excipients, preservatives, stabilizers, buffers, etc. (see, e.g., US’792 at ¶¶[0059]-[0060], [0062]-[0063]). Regarding claim 17, and the “wherein” clause reciting “when” at instant claim 1, per MPEP § 2111.04(II), the “wherein” clause reciting “wherein a pH is 3.0 to 4.5 when the pharmaceutical composition is dissolved in distilled water” is understood to be a contingent limitation that would necessarily be satisfied by an aqueous solution having a pH value of 3.0 to 4.5 and satisfying at least the structural requirements of claim 1(a).
The primary reference differs from instant claim 17 as follows: Although the primary reference teaches the exact polypeptide and identifies that such HMGB1 peptide fragments may be “formulated according to the usual methods”, the primary reference is silent regarding a formulation that has a pH of 3.0 to 4.5 in distilled water as required by the “wherein” clause at lines 2-3 of claim 1, which limits the aqueous formulation of claim 17.
Accordingly, the issue is whether or not it would have been routine and obvious in the pharmaceutical arts to formulate a peptide composition at a pH of 3.0 to 4.5.
Regarding instant claim 17, and the pH range of 3.0 to 4.5, it was routine in the prior art to screen over the range of pH 2 to 10 to identify optimal pH values for protein stability and solubility in pharmaceutical formulations: Nuijen pertains to the development and screening of pharmaceutical formulations for proteins, and establishes the ordinary skill in the art (see, e.g., Nuijen at title, abs). Nuijen identifies and discloses a basic study for developing a stable protein formulation for use in clinical trials (see, e.g., Nuijen at 768 at col I-II at bridging ¶), and does so by testing a variety of excipient formulations to identify an optimal formulation for protein “solubility and stability during formulation, freeze-drying, and storage” (see, e.g., Nuijen at 768 at col II at 1st full ¶). To find an optimal formulation for stability, Nuijen further screened multiple formulations “over the pH range of 2-10” to identify an optimal pH for solubility (see, e.g., Nuijen at 771 at col II at 2nd full ¶). Accordingly, one of ordinary skill in the protein pharmaceutical arts would be motivated to perform a routine screening of a peptide pharmaceutical formulation containing a protein of interest over the pH range of 2-10 to determine an optimal pH for the solubility and stability of a protein of interest (see, e.g., MPEP §§ 2144.05(I)-(II)).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The claimed invention is obvious because the general protein and pharmaceutical compositions are disclosed by the primary reference, and Nuijen establishes that it is routine and well-known in the art to screen protein-containing pharmaceutical formulations over the range of pH 2-10 to determine an optimal pH for the solubility and stability of a protein of interest; per MPEP § 2144.05(II), “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation”, at least because “[t]he normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages”; therefore “a mere carrying forward of an original [] conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent”; here, no criticality of range has been demonstrated and no unexpected results have been identified on record commensurate in scope with the requirements of MPEP 716.02, therefore the limitation regarding the pH values is understood to correspond to results of routine screening and optimization of the general conditions known and disclosed by the prior art of protein formulations (see, e.g., MPEP § 2144.05(II)).
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to make and screen pharmaceutical compositions comprising known components at known pH ranges to identify an optimal pH range.
Accordingly, claim 17 is rejected.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over US2015/0274792A1 (Oct. 1, 2015) and Nuijen et al9, as applied to claim 17 above, and further in view of Rowe et al10.
Claim interpretation: The applicable claim interpretation is set forth above in a separate section, and in preceding rejections. Those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below. This rejection addresses the limitations present in the originally elected species.
The teachings of US’792 and Nuijen as applied to claims 17 has been set forth in a preceding rejection, and those teachings are incorporated into the instant rejection.
US’792 and Nuijen differ from the originally elected species as follows: US’792 in view of Nuijen does not explicitly teach or direct artisans to a composition comprising instant SEQ ID NO: 1, Polysorbate 80, Citric Acid, and Sodium Hydroxide as instantly claimed.
As an initial matter, regarding claim 17, and the components of instant SEQ ID NO: 1, citric acid, sodium citrate, and sodium hydroxide: Each of the claimed components are prior art elements having known utility and typical concentration ranges:
Instant SEQ ID NO: 1 is taught and disclosed by the primary reference for use in treatment of spinal cord injuries (see, e.g., US’792 at claims 1-6, SEQ ID NO: 5), and taught for use, generally, in any pharmaceutical formulation at any pH and in combination with any excipients (see, e.g., US’792 at ¶¶[0059]-[0060], [0062]-[0063]), wherein a formulation may comprise 0.00001 mg to 100000 mg (see, e.g., US’792 at ¶[0062]), and wherein 0.5 mg/mL is exemplified (see, e.g., US’792 at ¶[0077], disclosing 100µg/200µL).
Polysorbate 80 is a prior art excipient (see, e.g., Rowe at 549-553). Rowe identifies that Polysorbate 80 is a prior art element (see, e.g., Rowe at 549 at §§ “1” and “4”, at 550 at Tables I-II), which acts as a dispersing agent, emulsifying agent, nonionic surfactant, solubilizing agent, suspending agent, and wetting agent in pharmaceutical formulations (see, e.g., Rowe at 550 at §§ “6” and “7”), and can improve bioavailability of drug molecules (see, e.g., Rowe at 550 at § “7”). Rowe identifies that Polysorbate 80 is typically utilized at concentrations of 0.1 to 15% (see, e.g., Rowe at 550 at Col. I at Table IV), and is generally recognized as safe (see, e.g., Rowe at 553 at § “16”).
Sodium Hydroxide is a prior art excipient (see, e.g., Rowe at 648-649), that is a “buffering agent”, that is “widely used in pharmaceutical formulations to adjust the pH of solutions” (see, e.g., Rowe at §§ “1”, “2”, “3”, “4”, “6”, and “7”).
Citric Acid is a prior art excipient (see, e.g., Rowe at 181-183). Rowe identifies that Citric Acid Hydrate is an art-recognized acidifying agent, antioxidant, buffering agent, chelating agent, and preservative (see, e.g., Rowe at 181 at §§ “1” and “6”) and is “widely used in pharmaceutical formulations . . . primarily to adjust the pH of solutions” (see, e.g., Rowe at 181 at § “7”), and is primarily utilized at concentrations of 0.1-2.0% (see, e.g., Rowe at 181 at § “7” at Table 1), and is considered GRAS (see, e.g., Rowe at 182 at § 16).
Accordingly, Rowe establishes that SEQ ID NO: 1, Polysorbate 80, Citric Acid, and Sodium Hydroxide are each prior art elements.
Furthermore, Nuijen exemplifies pharmaceutical compositions comprising different amounts of Polysorbate 80 and Citric Acid in combination with their protein of interest to find and optimize the concentrations of such components for a protein of interest, at multiple pH values “over the pH range of 2-10” to identify an optimal pH for solubility (see, e.g., Nuijen at 770 at Table 1, 769 at col II at final ¶ to 770 at col I at 1st partial ¶, 771 at col II at 2nd full ¶). Accordingly, the use of citric acid in protein formulations over a range of pH values ranging from 2-10 was known in the prior art (see id).
Regarding the use of sodium hydroxide to “adjust” pH, although Nuijen does not explicitly teach Sodium hydroxide as present in the originally elected species (see, e.g., Spec. filed 10/19/2022 at ¶[0111] at page 23 at Table 1, noting that NaOH is present in an “adequate amount” to achieve the recited pH of 3.0), Rowe discloses that sodium hydroxide is a prior art excipient (see, e.g., Rowe at 648-649), that is a “buffering agent”, that is “widely used in pharmaceutical formulations to adjust the pH of solutions” (see, e.g., Rowe at §§ “1”, “2”, “3”, “4”, “6”, and “7”). Accordingly, using an “adequate amount” of sodium hydroxide to achieve a required pH value within the range of pH values screened by Nuijen would be obvious, because it amounts to the use and selection of a known prior art element for its art-recognized purpose, wherein it achieves only the art-recognized purpose of adjusting a pH value (see, e.g., MPEP § 2144.07, noting that the selection of a known material based on its suitability for its intended use supports a determination of prima facie obviousness).
Regarding the usage of 5.0 mg/g of polysorbate 80 as present in the originally elected species, the originally elected species is understood to comprise “5.0” of polysorbate 80, wherein “5.0” is presumably in “mg/g” (0.001 g/g is 0.1 wt/wt%, so “5.0” is understood to be 0.5 wt/wt%) (see, e.g., Spec. filed 10/19/2022 at ¶[0111] at page 23 at Table 1). Furthermore, the originally elected species is understood to be a dilute aqueous solution primarily composed of water, and therefore because water is 1 gram per milliliter (1 g/mL), the originally elected species is understood to comprise approximately 0.5 wt/wt% or 0.5 wt/v% of polysorbate 80 (see, e.g., Spec. filed 10/19/2022 at ¶[0111] at page 23 at Table 1). This is pertinent because Nuijen discloses that polysorbate 80 may vary from 0.1 to 0.5 % w/v (see, e.g., Nuijen at 770 at Table 1, 769 at col II at final ¶ to 770 at col I at 1st partial ¶), and Rowe teaches that Polysorbate 80 is typically utilized at concentrations of 0.1 to 15% (see, e.g., Rowe at 550 at Col. I at Table IV). Accordingly, the amount of polysorbate 80 present in the elected species overlaps and lies inside the ranges taught and suggested by the prior art (see, e.g., MPEP § 2144.05, noting that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists). Furthermore, the component merely performs its art-recognized functions identified by Rowe (see, e.g., Rowe at 550 at §§ “6” and “7”).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The invention is the combination of prior art elements (i.e., SEQ ID NO: 1, polysorbate 80, citric acid, sodium hydroxide) according to known methods of forming and screening pharmaceutical formulations as taught and suggested by Nuijen and Rowe, wherein such combination would predictably yield a protein-containing pharmaceutical composition suitable for use in the applications taught and disclosed by the primary reference (see, e.g., MPEP §§ 2143(I)(A), 2144.05, 2144.07). Furthermore, each prior art component merely performs its art-recognized function when combined. Alternatively, the invention is obvious because it is the simple substitution of the peptide of the primary reference in place of the peptide of Nuijen, in the method of screening and formulation optimization taught by Nuijen, wherein such substitution would predictably and expectedly yield an optimized pharmaceutical formulation comprising instant SEQ ID NO: 1, polysorbate 80, citric acid, sodium hydroxide, and having a pH of between 2 and 10, wherein such optimized formulation would be usable in the applications and methods disclosed by the primary reference (see, e.g., MPEP §§ 2143(I)(B), 2143(I)(G), 2144.05, 2144.07).
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to make and screen pharmaceutical compositions comprising known components at known pH ranges to identify an optimal pH range.
Accordingly, claim 17 is rejected.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over US2015/0274792A1 (Oct. 1, 2015) and Nuijen et al11 in view of Rowe et al12.as applied to claim 17 above, and further in view of Shalaev et al13.
Claim interpretation: The applicable claim interpretation is set forth above in a separate section, and in preceding rejections. Those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
The teachings of US’792, Nuijen and Rowe as applied to claim 17 and the originally elected species has been set forth in a preceding rejection, and those teachings are incorporated into the instant rejection.
US’792 and Nuijen differ from the originally elected species as follows: US’792 in view of Nuijen and Rowe does not explicitly teach or direct artisans to further modify the pharmaceutical composition suggested by US’792, Nuijen, and Rowe by further adding the component of sodium citrate as present in the originally elected species.
Shalaev pertains to pharmaceutical formulations, and explains that “[m]any pharmaceuticals contain a buffer to control pH, to ensure optimal chemical and physical stability of a drug molecule” (see, e.g., Shalaev at title, abs, 195 at col I at Introduction), but explains that formulations intended to be lyophilized should avoid buffer components that may crystallize during freezing, because such changes can produce undesirable and significant pH changes that “should be avoided” (see id). Shalaev teaches and discloses that “sodium citrate” is the “preferred choice at pH 2.5 to 4.5” (see, e.g., Shalaev at 200 at col I at 1st full ¶), and identifies more generally that “Citrate would appear to be the buffer of choice for lyophilized formulations because it has a lower crystallization potential and a higher collapse temperature” (see, e.g., Shalaev at 200 at col II at 1st full ¶). Shalaev concludes that “Use of citrate buffer in freeze-dried formulations should be beneficial because of its relatively low crystallization potential and a higher collapse temperature” (see, e.g., Shalaev at 200 at col II at 2nd full ¶).
In addition, Rowe identifies that sodium citrate is an art-recognized buffering agent, emulsifying agent, and sequestering agent (see, e.g., Rowe at 640 at §§ “1”, “2”, “3”, “6”, and “7”; one of skill in the art would appreciate that a “sequestering agent” was also known as a chelating agent, and was an excipient that binds to trace amounts of metal ions to prevent them from interfering with a drug formulation). Rowe identifies that sodium citrate is “widely used in pharmaceutical formulations” and may be used “to adjust the pH of solutions” (see, e.g., Rowe at 640 at § “7”). Rowe identifies that sodium citrate is typically utilized at a concentration of 0.1 to 4.0% (see, e.g., Rowe at 641 at Table I).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): It would be obvious to add sodium citrate as taught and suggested by Shalaev and Rowe to the composition suggested in view of US’792, Nuijen, and Rowe, because sodium citrate would desirably act as a buffering agent and chelating agent as taught by Rowe, and would additionally facilitate and protect against changes in pH during lyophilization as taught by Shalaev, and wherein such combination would predictably yield a protein-containing pharmaceutical composition suitable for use in the applications taught and disclosed by the primary reference, advantageously having the added activities and protections during lyophilization as taught by Shalaev (see, e.g., MPEP §§ 2143(I)(A), 2144.05, 2144.07). Furthermore, each component is a prior art element that merely performs its art-recognized function when used in combination.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to make and screen pharmaceutical compositions comprising known components at known pH ranges to identify an optimal pH range.
Accordingly, claim 17 is rejected.
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.
Claim 17 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 11969459 B2 in view of Nuijen et al14.
Claim Interpretation: The Applicable claim interpretation is set forth above. Additional claim interpretations are set forth below.
The applicable analysis for Nonstatutory Double Patenting is set forth at MPEP § 804(II), and specifically at MPEP § 804(II)(B). Per MPEP § 804(II)(B), “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.” Accordingly, a comparison of the teachings of the reference claims and the instant pending claims are set forth below:
The primary reference pertains to methods of using pharmaceutical compositions comprising instant SEQ ID NO: 1 as required by instant claims 17 and 1(a) (compare instant claim 1(a) and SEQ ID NO: 1 with US’459 at claim 1-28 and SEQ ID NO: 1, showing 100% sequence identity). Accordingly, in view of methods of using a pharmaceutical composition, an artisan would readily and necessarily appreciate that such methods required and necessitated the existence of a pharmaceutical composition comprising SEQ ID NO: 1.
The issued claims differ from the instantly pending claims as follows: Although the primary reference claims methods that necessarily use and require the existence of pharmaceutical compositions comprising the same exact polypeptide recited at instant claim 1(a), the issued claims do not (i) explicitly require a formulation that has a pH of 3.0 to 4.5 as required by the “wherein” clause at lines 2-3 of claim 1 and therefore examined claim 17 or (ii) require citric acid.
Accordingly, the relevant issue is whether or not a pH limitation and the presence of the pharmaceutical excipient of citric acid is sufficient to patentably distinguish the issued claims from the instantly pending claims.
Per MPEP § 804(II)(B)(1), it is permissible to consult the Specification of an issued patent to identify what constitutes an obvious variant (see, e.g., MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”). Here, the primary reference informs artisans that pharmaceutical compositions used in the claimed methods may comprise a broad dosage of the recited peptide (see, e.g., US’459 at col. 15 at lines 40-50), and that such pharmaceutical compositions may be “formulated according to conventional methods” and “may contain pharmaceutically acceptable carriers and additives”, including any excipients, preservatives, stabilizers, surfactants, binding agents, suspending agents, isotonizing agents, etc., without limit (see, e.g., US’459 at col. 15 at lines 54-65). Accordingly, the pharmaceutical compositions necessarily utilized by the claimed methods would necessarily and inherently comprise a pH value selected from an unspecified pH range, and would also comprise one or more excipients and/or carriers (see id.). Accordingly, the relevant issue is whether or not specifying a smaller pH range patentably distinguishes the issued claims relative to the instant claims 1 and 17, and whether or not specifying a particular prior art excipient patentably distinguishes the issued claims relative to instant claims.
Nuijen establishes the ordinary skill in the pharmaceutical arts circa 2001, and specifically pertains to routine screening and optimization steps performed to develop and obtain stable pharmaceutical formulations for use in clinical studies (see, e.g., Nuijen at title, abs). Nuijen identifies and discloses a basic study for developing a stable protein formulation for use in clinical trials (see, e.g., Nuijen at 768 at col I-II at bridging ¶), and does so by testing a variety of excipient formulations to identify an optimal formulation for protein “solubility and stability during formulation, freeze-drying, and storage” (see, e.g., Nuijen at 768 at col II at 1st full ¶). Nuijen exemplifies, evidences and establishes that optimization of stable protein formulations for use in clinical trials included making and screening multiple formulations “over the pH range of 2-10” to identify an optimal pH for solubility, was routine in the prior art (see, e.g., Nuijen at 771 at col II at 2nd full ¶). In addition, Nuijen exemplifies, evidences, and establishes that optimization of stable protein formulations for use in clinical trials included testing multiple amounts of citric acid in combination with their protein of interest to find and optimize the concentrations of such components for a protein of interest, at multiple pH values “over the pH range of 2-10” to identify an optimal pH for solubility (see, e.g., Nuijen at 770 at Table 1, 769 at col II at final ¶ to 770 at col I at 1st partial ¶, 771 at col II at 2nd full ¶). Accordingly, the use of citric acid in protein formulations over a range of pH values ranging from 2-10 was known in the prior art, and Nuijen establishes that such screening and developmental studies was routine in the pharmaceutical arts (compare id. with instant claims).
Obviousness analysis: Under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is noted that the scope and content of the patent claim relative to the application claims at issue have been discussed above (see, e.g., MPEP § 804(II)(B)(3)(A)). Here the differences are minimal because the methods of the issued claims necessarily require the existence of a pharmaceutical formulation having an unspecified pH, unspecified excipients, but comprising the exact same active agent polypeptide as the presently claimed compositions; therefore, the issued claims are understood to require and utilize any formulation or pH of pharmaceutical compositions comprising the same polypeptide. The only difference is that the instant claims are directed to the pharmaceutical composition, and further limit to a specific pH range and to comprise a specific, prior art excipient. However, as established by Nuijen, optimizing the pH of a pharmaceutical formulation over the range of 2-10 and utilizing the art-recognized excipient of citric acid is routine in the pharmaceutical arts, because artisans typically make and screen multiple pharmaceutical compositions to obtain optimal protein stability and solubility for use in clinical applications. Accordingly, the present claims are directed to obvious variants of the representative claims because it is well-within the ordinary skill in the art to make, use, and screen pharmaceutical compositions using routine optimization screens known in the prior art, such as the one disclosed by Nuijen, wherein performing such screening and optimization steps would desirably and beneficially result in a citric acid containing pharmaceutical composition having a pH of 2-10 that was useful in the practice of the claimed methods of the issued patent (see, e.g., MPEP § 804(II)(B)(3); see also MPEP §§ 2143(I)(A), (B), (C), (G), 2144.05(I)-(II)). Stated alternatively, the instant claims would be the obvious result of simply making and optimizing pharmaceutical compositions used in the issued claims, wherein such making and optimizing could be performed by simply substituting the composition of the issued claims into the prior art optimizing and screening methodology taught by Nuijen (see, e.g., MPEP § 804(II)(B)(3); see also MPEP §§ 2143(I)(A), (B), (C), (G), 2144.05(I)-(II)). In sum, the minor differences cannot be said to patentably distinguish the instant claims relative to the issued claims.
Accordingly, the pending claims are obvious in view of the issued claims in view of Nuijen.
Claim 17 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11298403 B2 in view of Nuijen et al15.
Claim Interpretation: The Applicable claim interpretation is set forth above. Additional claim interpretations are set forth below.
The applicable analysis for Nonstatutory Double Patenting is set forth at MPEP § 804(II), and specifically at MPEP § 804(II)(B). Per MPEP § 804(II)(B), “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.” Accordingly, a comparison of the teachings of the reference claims and the instant pending claims are set forth below:
The primary reference pertains to methods of using pharmaceutical compositions comprising instant SEQ ID NO: 1 as required by instant claim 1(a) and therefore claim 17 (compare instant claim 1(a), SEQ ID NO: 1 with US’403 at claims 1-5, SEQ ID NO: 1, showing 100% identity). Accordingly, in view of methods of using a pharmaceutical composition, an artisan would readily and necessarily appreciate that such methods required and necessitated the existence of a pharmaceutical composition comprising SEQ ID NO: 1.
The issued claims differ from the instantly pending claims as follows: Although the primary reference claims methods that necessarily use and require the existence of pharmaceutical compositions comprising the same exact polypeptide recited at instant claim 1(a), the issued claims do not (i) explicitly require a formulation that has a pH of 3.0 to 4.5 as required by the “wherein” clause at lines 2-3 of claim 1 and therefore instant claim 17 or (ii) require citric acid.
Accordingly, the relevant issue is whether or not a pH limitation and the presence of the pharmaceutical excipient of citric acid is sufficient to patentably distinguish the issued claims from the instantly pending claims.
Per MPEP § 804(II)(B)(1), it is permissible to consult the Specification of an issued patent to identify what constitutes an obvious variant (see, e.g., MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”). Here, the primary reference informs artisans that pharmaceutical compositions used in the claimed methods may comprise a broad dosage of the recited peptide (see, e.g., US’403 at col. 7 at lines 4-12), and that such pharmaceutical compositions may be “formulated according to conventional methods” and “may contain pharmaceutically acceptable carriers and additives”, including any excipients, preservatives, stabilizers, surfactants, binding agents, suspending agents, isotonizing agents, etc., without limit (see, e.g., US’403 at col. 7 at lines 15-30). Accordingly, the pharmaceutical compositions necessarily utilized by the claimed methods would necessarily and inherently comprise a pH value selected from an unspecified pH range, and would also comprise one or more excipients and/or carriers (see id.). Accordingly, the relevant issue is whether or not specifying a smaller pH range patentably distinguishes the issued claims relative to the instant claim 17, and whether or not specifying a particular prior art excipient patentably distinguishes the issued claims relative to instant claim.
Nuijen establishes the ordinary skill in the pharmaceutical arts circa 2001, and specifically pertains to routine screening and optimization steps performed to develop and obtain stable pharmaceutical formulations for use in clinical studies (see, e.g., Nuijen at title, abs). Nuijen identifies and discloses a basic study for developing a stable protein formulation for use in clinical trials (see, e.g., Nuijen at 768 at col I-II at bridging ¶), and does so by testing a variety of excipient formulations to identify an optimal formulation for protein “solubility and stability during formulation, freeze-drying, and storage” (see, e.g., Nuijen at 768 at col II at 1st full ¶). Nuijen exemplifies, evidences and establishes that optimization of stable protein formulations for use in clinical trials included making and screening multiple formulations “over the pH range of 2-10” to identify an optimal pH for solubility, was routine in the prior art (see, e.g., Nuijen at 771 at col II at 2nd full ¶). In addition, Nuijen exemplifies, evidences, and establishes that optimization of stable protein formulations for use in clinical trials included testing multiple amounts of citric acid in combination with their protein of interest to find and optimize the concentrations of such components for a protein of interest, at multiple pH values “over the pH range of 2-10” to identify an optimal pH for solubility (see, e.g., Nuijen at 770 at Table 1, 769 at col II at final ¶ to 770 at col I at 1st partial ¶, 771 at col II at 2nd full ¶). Accordingly, the use of citric acid in protein formulations over a range of pH values ranging from 2-10 was known in the prior art, and Nuijen establishes that such screening and developmental studies was routine in the pharmaceutical arts (compare id. with instant claims).
Obviousness analysis: Under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is noted that the scope and content of the patent claim relative to the application claims at issue have been discussed above (see, e.g., MPEP § 804(II)(B)(3)(A)). Here the differences are minimal because the methods of the issued claims necessarily require the existence of a pharmaceutical formulation having an unspecified pH, unspecified excipients, but comprising the exact same active agent polypeptide as the presently claimed compositions; therefore, the issued claims are understood to require and utilize any formulation or pH of pharmaceutical compositions comprising the same polypeptide. The only difference is that the instant claims are directed to the pharmaceutical composition, and further limit to a specific pH range and to comprise a specific, prior art excipient. However, as established by Nuijen, optimizing the pH of a pharmaceutical formulation over the range of 2-10 and utilizing the art-recognized excipient of citric acid is routine in the pharmaceutical arts, because artisans typically make and screen multiple pharmaceutical compositions to obtain optimal protein stability and solubility for use in clinical applications. Accordingly, the present claims are directed to obvious variants of the representative claims because it is well-within the ordinary skill in the art to make, use, and screen pharmaceutical compositions using routine optimization screens known in the prior art, such as the one disclosed by Nuijen, wherein performing such screening and optimization steps would desirably and beneficially result in a citric acid containing pharmaceutical composition having a pH of 2-10 that was useful in the practice of the claimed methods of the issued patent (see, e.g., MPEP § 804(II)(B)(3); see also MPEP §§ 2143(I)(A), (B), (C), (G), 2144.05(I)-(II)). Stated alternatively, the instant claims would be the obvious result of simply making and optimizing pharmaceutical compositions used in the issued claims, wherein such making and optimizing could be performed by simply substituting the composition of the issued claims into the prior art optimizing and screening methodology taught by Nuijen (see, e.g., MPEP § 804(II)(B)(3); see also MPEP §§ 2143(I)(A), (B), (C), (G), 2144.05(I)-(II)). In sum, the minor differences cannot be said to patentably distinguish the instant claims relative to the issued claims.
Accordingly, the pending claims are obvious in view of the issued claims in view of Nuijen.
Claim 17 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 9688733 B216 in view of Nuijen et al17.
Claim Interpretation: The Applicable claim interpretation is set forth above. Additional claim interpretations are set forth below.
The applicable analysis for Nonstatutory Double Patenting is set forth at MPEP § 804(II), and specifically at MPEP § 804(II)(B). Per MPEP § 804(II)(B), “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.” Accordingly, a comparison of the teachings of the reference claims and the instant pending claims are set forth below:
The primary reference pertains to methods of using pharmaceutical compositions comprising instant SEQ ID NO: 5 as required by instant claim 1(a) and claim 17 (compare instant claim 1(a), SEQ ID NO: 1 with US’733 at claims 1-2, SEQ ID NO: 5, showing 100% identity). Accordingly, in view of methods of using a pharmaceutical composition, an artisan would readily and necessarily appreciate that such methods required and necessitated the existence of a pharmaceutical composition comprising SEQ ID NO: 5.
The issued claims differ from the instantly pending claims as follows: Although the primary reference claims methods that necessarily use and require the existence of pharmaceutical compositions comprising the same exact polypeptide recited at instant claim 1(a), the issued claims do not (i) explicitly require a formulation that has a pH of 3.0 to 4.5 as required by the “wherein” clause at lines 2-3 of claim 1 and therefore claim 17 or (ii) require citric acid.
Accordingly, the relevant issue is whether or not a pH limitation and the presence of the pharmaceutical excipient of citric acid is sufficient to patentably distinguish the issued claims from the instantly pending claims.
Per MPEP § 804(II)(B)(1), it is permissible to consult the Specification of an issued patent to identify what constitutes an obvious variant (see, e.g., MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”). Here, the primary reference informs artisans that pharmaceutical compositions used in the claimed methods may comprise a broad dosage of the recited peptide (see, e.g., US’733 at col. 8 at line 63 to col. 9 at line 5), and that such pharmaceutical compositions may be “formulated according to conventional methods” and “may contain pharmaceutically acceptable carriers and additives”, including any excipients, preservatives, stabilizers, surfactants, binding agents, suspending agents, isotonizing agents, etc., without limit (see, e.g., US’733 at col. 9 at lines 10-25). Accordingly, the pharmaceutical compositions necessarily utilized by the claimed methods would necessarily and inherently comprise a pH value selected from an unspecified pH range, and would also comprise one or more excipients and/or carriers (see id.). Accordingly, the relevant issue is whether or not specifying a smaller pH range patentably distinguishes the issued claims relative to the instant claim 17, and whether or not specifying a particular prior art excipient patentably distinguishes the issued claims relative to instant claims.
Nuijen establishes the ordinary skill in the pharmaceutical arts circa 2001, and specifically pertains to routine screening and optimization steps performed to develop and obtain stable pharmaceutical formulations for use in clinical studies (see, e.g., Nuijen at title, abs). Nuijen identifies and discloses a basic study for developing a stable protein formulation for use in clinical trials (see, e.g., Nuijen at 768 at col I-II at bridging ¶), and does so by testing a variety of excipient formulations to identify an optimal formulation for protein “solubility and stability during formulation, freeze-drying, and storage” (see, e.g., Nuijen at 768 at col II at 1st full ¶). Nuijen exemplifies, evidences and establishes that optimization of stable protein formulations for use in clinical trials included making and screening multiple formulations “over the pH range of 2-10” to identify an optimal pH for solubility, was routine in the prior art (see, e.g., Nuijen at 771 at col II at 2nd full ¶). In addition, Nuijen exemplifies, evidences, and establishes that optimization of stable protein formulations for use in clinical trials included testing multiple amounts of citric acid in combination with their protein of interest to find and optimize the concentrations of such components for a protein of interest, at multiple pH values “over the pH range of 2-10” to identify an optimal pH for solubility (see, e.g., Nuijen at 770 at Table 1, 769 at col II at final ¶ to 770 at col I at 1st partial ¶, 771 at col II at 2nd full ¶). Accordingly, the use of citric acid in protein formulations over a range of pH values ranging from 2-10 was known in the prior art, and Nuijen establishes that such screening and developmental studies was routine in the pharmaceutical arts (compare id. with instant claims).
Obviousness analysis: Under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is noted that the scope and content of the patent claim relative to the application claims at issue have been discussed above (see, e.g., MPEP § 804(II)(B)(3)(A)). Here the differences are minimal because the methods of the issued claims necessarily require the existence of a pharmaceutical formulation having an unspecified pH, unspecified excipients, but comprising the exact same active agent polypeptide as the presently claimed compositions; therefore, the issued claims are understood to require and utilize any formulation or pH of pharmaceutical compositions comprising the same polypeptide. The only difference is that the instant claims are directed to the pharmaceutical composition, and further limit to a specific pH range and to comprise a specific, prior art excipient. However, as established by Nuijen, optimizing the pH of a pharmaceutical formulation over the range of 2-10 and utilizing the art-recognized excipient of citric acid is routine in the pharmaceutical arts, because artisans typically make and screen multiple pharmaceutical compositions to obtain optimal protein stability and solubility for use in clinical applications. Accordingly, the present claims are directed to obvious variants of the representative claims because it is well-within the ordinary skill in the art to make, use, and screen pharmaceutical compositions using routine optimization screens known in the prior art, such as the one disclosed by Nuijen, wherein performing such screening and optimization steps would desirably and beneficially result in a citric acid containing pharmaceutical composition having a pH of 2-10 that was useful in the practice of the claimed methods of the issued patent (see, e.g., MPEP § 804(II)(B)(3); see also MPEP §§ 2143(I)(A), (B), (C), (G), 2144.05(I)-(II)). Stated alternatively, the instant claims would be the obvious result of simply making and optimizing pharmaceutical compositions used in the issued claims, wherein such making and optimizing could be performed by simply substituting the composition of the issued claims into the prior art optimizing and screening methodology taught by Nuijen (see, e.g., MPEP § 804(II)(B)(3); see also MPEP §§ 2143(I)(A), (B), (C), (G), 2144.05(I)-(II)). In sum, the minor differences cannot be said to patentably distinguish the instant claims relative to the issued claims.
Accordingly, the pending claims are obvious in view of the issued claims in view of Nuijen.
Response to Arguments
Applicant's arguments filed 3/26/2026 have been fully considered but they are not persuasive. Examiner notes that multiple arguments have been rendered moot in view of withdrawn rejections. Applicable arguments are addressed below.
Claim Interpretation
It is undisputed that the originally elected species of Example 1 is an aqueous, injectable composition, comprising water and having a pH of 3.0 (see, e.g., Spec. filed 10/19/2022 at ¶[0111] at page 23 at Table 1).
It is the Examiner’s understanding that Applicant is now further clarifying18 that the originally elected species did not properly read upon all pending claims as originally indicated by Applicant (see, e.g., Reply to Requirement filed 10/27/2025 at 3 of 4, alleging that “All Group I claims read on the elected species”). Notably, the Examiner had previously identified on record that this assertion was incorrect at least with respect to claims 5-10 and 14-16 (see, e.g., Action mailed 1/02/2026 at 3-4 at bridging ¶). However, it is now the Examiner’s understanding that Applicant is identifying that additional pending claims within Group I do not read upon the originally elected species because such claims do not encompass aqueous compositions (see, e.g., Reply filed 3/26/2026 at 6-7 at § Claim Interpretation).
Specifically, it is the Examiner’s understanding that Applicant is alleging that the interpretation of instant claim 1 was “overly broad and should be reconsidered” because the limitation is not “satisfied by virtually any injectable aqueous composition capable of exhibiting a pH within that range”, and that by examining claims 1 and 17 as both reading upon the originally elected species, the Examiner has improperly “effectively read it out of the claim” (see, e.g., Reply filed 3/26/2026 at 6-7 at § Claim Interpretation19; referring to Action mailed 1/02/2026 at 6 at 3rd ¶, wherein the Examiner explained that the contingent language at claim 1 was deemed satisfied by “any aqueous pharmaceutical composition capable of being injected that has a pH between 3.0 to 4.5”). Examiner has reviewed the arguments and the record. Examiner concurs that Claim 1 clearly and unambiguously recites “when the pharmaceutical composition is dissolved in distilled water”, wherein the word “when” presupposes that the limitation is not yet met or present in the product being claimed. Therefore, the pharmaceutical composition recited at claim 1 has not yet been “dissolved in distilled water”, and therefore the product claimed at instant claim 1 is understood to excludes distilled water since distilled water is not yet added. This interpretation is reasonable because dependent claim 15 identifies and confirms that the product of claim 1 may be a freeze-dried product (i.e., a non-aqueous solid, powder, etc.). Furthermore, claim 17 is understood to satisfy 35 USC 112(d), and differs from claim 1 by the addition of water. Accordingly, claim 1 is understood to be directed to a non-aqueous powder, granules, or other solid that are “capable of” having a pH of 3.0 to 4.5 “when” dissolved in water; therefore, claim 1 does not read upon the originally elected species because the originally species is an aqueous composition. Therefore, Applicant’s arguments have been fully considered (see, e.g., Reply filed 3/26/2026 at 6-7 at § Claim Interpretation), and claim 1 is understood to not read upon the elected species and to not be an obvious variant of the originally elected species in view of the instant record. In view of the elected species and Applicant’s arguments, claim 17 is currently the only claim of record reciting and requiring the presence of water, as actually present in the originally elected species of Example 1 (note that the buffer utilized comprises water, and water is present as indicated by reference to a pH)20.
The rejections have been revised to clarify that (i) only the originally elected species has been examined, (ii) claim 17 is the only pending claim that appears to unambiguously read upon the originally elected species, and (iii) examination has not been extended to any other non-elected species or non-obvious variants of the originally elected species at this time. The originally elected species was therefore correctly and fully examined and deemed obvious in the prior action and rejections of record, and those rationales and citations are maintained.
Arguments Regarding Rejections under 35 USC 103
It is the Examiner’s understanding that Applicant traverses the rejections under 35 USC 103 at pages 9-13 (see, e.g., Reply filed 3/26/2026 at 9 at § “Rejections under 35 U.S.C. § 103” to page 13 at 4th full ¶).
Examiner acknowledges statements made in the absence of arguments: It is the Examiner’s understanding that Applicant recites the rejections (see, e.g., Reply filed 3/26/2026 at 9 at § “Rejections under 35 U.S.C. § 103”), alleges that they do not concede that prima facie obviousness has been established (see, e.g., Reply filed 3/26/2026 at 10 at 1st and 2nd ¶¶); and then recites applicable U.S. case law without applying the facts of the cited cases to the instant fact pattern (see, e.g., Reply filed 3/26/2026 at 10 at 2nd and 3rd full ¶¶). These statements do not address the merits of the rejections of record or otherwise identify how the claimed invention is patentably distinguishable over the prior art of record.
All claimed limitations were explicitly addressed: It is the Examiner’s understanding that Applicant is suggesting that the Examiner did not address all claimed limitations, and appears to refer to the pH range of 3.0 to 4.5 (see, e.g., Reply filed 3/26/2026 at 10-11 at bridging ¶ to page 11 at final ¶). This argument is not persuasive because the rejections of record explicitly address the pH range presently claimed. In brief, the rejection establishes that US2015/0274792A1 teaches and discloses pharmaceutical compositions comprising the exact same polypeptide as instantly claimed, wherein such pharmaceutical compositions would be understood to necessarily and inherently encompass all relevant pH values for pharmaceutical applications, but wherein US’792 is silent regarding pH values. However, typical pH values are identified in view of Nuijen et al21, and are understood to be routinely range from a pH of 2-10, wherein it is routine in the prior art to optimize pH values (see, e.g., Nuijen at title, abs, 768 at col I-II at bridging ¶, 768 at col II at 1st full ¶, 771 at col II at 2nd full ¶, 770 at Table 1, 769 at col II at final ¶ to 770 at col I at 1st partial ¶, 771 at col II at 2nd full ¶). Accordingly, the rejection unambiguously addresses all limitations recited in pending and examined claim 17, and Applicant fails to identify any limitation that was not fully considered in the rejections of record.
Rationales supporting a determination of obviousness were explicitly identified on record by the Examiner: It is the Examiner’s understanding that Applicant is suggesting that the Examiner did not identify a rationale supporting a determination of prima facie obviousness (see, e.g., Reply filed 3/26/2026 at 10-11 at bridging ¶ to page 11 at final ¶). In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, the Examiner expressly identified multiple rationales supporting a determination of obviousness, including rationales under MPEP § 2144.05(II), § 2143(I)(A), § 2143(I)(B), § 2144.05, § 2144.07. Notably, Applicant fails to acknowledge these rationales, address these rationales, or identify a single element of such rationales that is not satisfied. Accordingly, arguments alleging that the Examiner failed to identify rationale(s) supporting a determination of prima facie obviousness are factually incorrect and therefore not persuasive.
Examiner may rely upon a rationale that differs from the Applicant’s rationale for arriving at the claimed invention: It is the Examiner’s understanding that Applicant is suggesting that the Examiner did not establish obviousness using the same rationale relied upon by the Applicant to arrive at the claimed invention (see, e.g., Reply filed 3/26/2026 at 10-11 at bridging ¶ to page 11 at final ¶). Examiner notes that this is not persuasive because an examiner may support a determination of obviousness by relying upon a rationale that differs from the Applicant’s rationale (see, e.g., MPEP § 2144(IV)). Here, the Examiner’s rationales are explicitly identified in the rejection (e.g., MPEP § 2144.05(II), § 2143(I)(A), § 2143(I)(B), § 2144.05, § 2144.07), but Applicant fails to address or specifically dispute these rationales supporting a determination of obviousness. Accordingly, such arguments are not persuasive.
Although the primary reference is silent regarding pH values, the claims and disclosure necessarily encompasses all injectable pharmaceutical compositions having pharmaceutically relevant pH values, which the secondary reference establishes is a pH of 2-10: It is the Examiner’s understanding that Applicant does not appreciate that the primary reference discloses compositions that must necessarily and inherently possess pH values (see, e.g., US’792 at claims 1-2 and 4-5), and that the primary reference only differs from the instant claims because the primary reference is silent regarding the pH values encompassed by the claims (see, e.g., Reply filed 3/26/2026 at 10-11 at bridging ¶ to page 11 at final ¶, 12 at 1st full ¶). This is pertinent because US’792 clearly identifies that the claimed embodiments may comprise various excipients (see, e.g., US’792 at ¶[0063]), and that the claimed pharmaceutical compositions included injection formulations (see, e.g., US’792 at claims 1-2 and 4-5, ¶¶[0059]-[0060]). Accordingly, one of ordinary skill in the art would readily appreciate and know that US’792 at claims 1-2 and 4-5 encompassed all pharmaceutical compositions comprising the same peptide and having all pH ranges suitable for injection formulations, consistent with the disclosure of US’792, as explained in the rejection. The secondary reference evidences and establishes that this necessarily present pH range would be recognized by one of ordinary skill in the art to necessarily include pH values of at least 2 to 10, which overlaps with the pending claim scope (see, e.g., MPEP § 2144.05(I), noting that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists). Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses or reasonably suggests, including alternative and non-preferred embodiments (see, e.g., MPEP §§ 2123(I)-(II)), including all pharmaceutical compositions at all pH values suitable for use in injections as taught and disclosed by the primary reference. As explained at MPEP § 2144.05(II), generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Here, no criticality of range has been established commensurate in scope with the requirements of MPEP § 716.02, and the only difference between the claimed invention and the prior art is that the prior art encompasses any injectable pharmaceutical composition at any pharmaceutically relevant pH value (see, e.g., MPEP § 2121(I), §§ 2123(I)-(II)). This is pertinent because, per KSR, all that is needed to sustain a determination of obviousness is:
A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007).
"[W]hen a patent 'simply arranges old elements with each performing the same function it had been known to perform' and yields no more than one would expect from such an arrangement, the combination is obvious." KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 , 417 , 127 S. Ct. 1727 , 167 L. Ed. 2d 705 (2007) (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273 , 282 , 96 S. Ct. 1532 , 47 L. Ed. 2d 784 (1976)).
Accordingly, here all components were known in the prior art, the function of each component was known in the prior art, one of skill in the art could combine such known components, and such combination yields “no more than one would expect from such an arrangement”. Furthermore, the Court has stated that
"[W]hen a patent 'simply arranges old elements with each performing the same function it had been known to perform' and yields no more than one would expect from such an arrangement, the combination is obvious."
KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 , 417 , 127 S. Ct. 1727 , 167 L. Ed. 2d 705 (2007) (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273 , 282 , 96 S. Ct. 1532 , 47 L. Ed. 2d 784 (1976));
and has also emphasized that
“If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.”
KSR Int'l v. Teleflex Inc., 550 U.S. 398, 415 (2007), at 417.
Here, as explained in the rejection above, all elements of the invention are all prior art elements, all elements were routinely utilized in pharmaceutical compositions, and each component would merely serve its art-recognized purpose in combination as it does separately. Accordingly, in the absence of any unexpected results commensurate in scope with the requirements of MPEP § 716.02, such combinations are within the scope of the teachings of the primary reference, and would merely be expected to perform as claimed by the primary reference.
Applicant addresses the prior art individually, rather than in combination: It is the Examiner’s understanding that Applicant addresses US’792 alone (see, e.g., Reply filed 3/26/2026 at 12 at 1st ¶) and Nuijen alone (see, e.g., Reply filed 3/26/2026 at 12 at 2nd ¶ to 3rd full ¶). In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
It is the Examiner’s understanding that Applicant is alleging that “routine-optimization” of pH is improper: It is the Examiner’s understanding that Applicant is alleging that “routine-optimization” of pH is improper in view of Nuijen because Nuijen “does not disclose a continuous or systematic optimization across that entire range” (see, e.g., Reply filed 3/26/2026 at 12 at 2nd ¶). This is not persuasive because it does not reflect the ordinary level of skill in the art or the caselaw and explanations set forth at MPEP § 2144.05(II). Here, the primary reference teaches, claims, and/or discloses all pharmaceutical compositions comprising the same peptide instantly claimed and suitable for injection, wherein such compounds necessarily and inherently have an unbounded pH value (see, e.g., US’792 at claims 1-2 and 4-5, ¶¶[0059]-[0060]). The primary reference is presumed fully enabled for the entire unbounded and undisclosed range of pH values in the absence of evidence to the contrary (see, e.g., MPEP § 2121(I), §§ 2123(I)-(II)). However, US’792 is silent regarding what exact pH values are acceptable for injectable pharmaceutical compositions comprising a polypeptide; the secondary reference discloses and evidences that this range includes at least a pH value of 2-10. Notably, Nuijen need not disclose “a continuous or systematic optimization across that entire range” to sustain a rejection under MPEP § 2144.05(II)(see, e.g., Reply filed 3/26/2026 at 12 at 2nd ¶) because MPEP § 2144.05(II) explains that changes in a known result-effective variable within a known range are routine (see, e.g., MPEP § 2144.05(II)(A), noting that “differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”). Accordingly, a suggestion that one of ordinary skill in the art would not know how to adjust a pH value within a known range of 2-10 is not persuasive in the absence of supporting evidence, because adjusting pH values is understood to be routine in the art. Accordingly, an explicit teaching of “a continuous or systematic optimization across that entire range” is not required to sustain a rejection based upon routine optimization of a known parameter within a known range that overlaps the instantly claimed ranges (see also MPEP § 2144.05(I), explaining that “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”, and explaining that “A range can be disclosed in multiple prior art references instead of in a single prior art reference”). Furthermore, Rowe clearly establishes that adjusting pH values was well-within the ordinary skill in the art (see, e.g., rejections, above). Accordingly, such arguments are not persuasive because it is tantamount to alleging lack of enablement for adjusting pH, which is not credible in view of the instant record.
Nuijen does not “teach away” from the claimed invention: It is the Examiner’s understanding that Applicant is alleging that Nuijen teaches away from the claimed invention (see, e.g., Reply filed 3/26/2026 at 12 at 3rd to 4th ¶¶, alleging that “Nuijen’s results run counter to predictability”, and that “Nuijen is better understood as evidence against the Examiner’s position”). Examiner notes that this argument is not persuasive because none of prior art references at issue “teach away” from the claimed invention since they do not actually “criticize, discredit, or otherwise discourage the solution claimed” (see, e.g., MPEP § 2141.02(VI)). Applicant has not identified any disclosure that “criticizes, discredits, or otherwise discourages the solution claimed”, or otherwise identifies that an artisan in the injectable pharmaceutical peptide formulation arts would not conclude that such compositions could have pH values ranging from 2-10. The pH value corresponding to degradation of an unclaimed peptide occurred at a pH value of 2.6, which is not presently claimed; rather, the rejection relies upon the teachings of Nuijen that confirm that injectable peptide compositions are known to have pH values ranging from 2-10, and that artisans appreciate that pH values can be routinely optimized to find appropriate pH values within this range for peptides (see rejection, above). Regarding the alleged “trial-and-error nature” (see, e.g., Reply filed 3/26/2026 at 12 at 3rd ¶), “trial-and-error” is commonplace, routine, and expected in optimization experiments, and therefore routine testing over a known pH range is still routine, and predictably yields an optimized pH. Accordingly, no “teaching away” has been identified on record.
Applicant addresses Rowe and Shalaev individually, rather than in combination: It is the Examiner’s understanding that Applicant addresses Rowe and Shalaev alone (see, e.g., Reply filed 3/26/2026 at 12 at 5th ¶ to 13 at 1st partial ¶, 13 at 1st full ¶). In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Here, the teachings of Rowe have not been applied alone, and Applicant fails to consider the guidance provided by Nuijen regarding the selection of specific components such as polysorbate 80 and citric acid in combination with their protein of interest to find and optimize the concentrations of such components for a protein of interest, at multiple pH values “over the pH range of 2-10” (see, e.g., Nuijen at 770 at Table 1, 769 at col II at final ¶ to 770 at col I at 1st partial ¶, 771 at col II at 2nd full ¶). Accordingly, arguments addressing Rowe alone are not persuasive.
It is the Examiner’s understanding that Applicant may be suggesting that the full scope of their own pending claims are not fully enabled: It is the Examiner’s understanding that Applicant is alleging that the Applicant’s art suffers from “unpredictability” and has a “trial-and-error nature” (see, e.g., Reply filed 3/26/2026 at 12 at 3rd ¶), and that “excipient selection must be evaluated carefully on a case-by-case basis and cannot be assumed to be routine or predictable” (see, e.g., Reply filed 3/26/2026 at 13-14 at bridging ¶). Such statements suggest that enablement in this particular art requires explicit disclosures regarding specific excipient selections on a “case-by-case basis”; critically, such disclosures are lacking from Applicant’s own disclosure relative to the pending claim scope. Therefore, if Applicant is suggesting that a patent application in the instant art must satisfy a high bar to be fully enabled and operable, then Applicant should so clearly admit on record; however, such arguments and evidence would be considered in view of the limited disclosures provided in the instant disclosure. Notably, the instant claims are open-ended with respect to excipients of any kind (see, e.g., instant claim 17), and presumably read upon an infinite number of variations with numerous concentrations of numerous excipients. Accordingly, if enablement of such scope requires “case-by-case” guidance for each possible excipient, then in the absence of such guidance on the instant record, the instant claims would be rejected as not fully enabled for the same rationale Applicant is attempting to apply to the prior art. However, at this time, for purposes of the instant examination, Examiner assumes that both the instant disclosure and the prior art are fully enabled, absent objective evidence to the contrary.
Arguments alleging inoperability or lack of enabling disclosure: It is the Examiner’s understanding that Applicant is suggesting that the prior art is inoperable or otherwise not completely enabling (see, e.g., Reply filed 3/26/2026 at 12 at 3rd ¶, 13-14 at bridging ¶). Prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). The burden is on the Applicant to rebut the presumption of operability (see, e.g., MPEP § 2121(I); MPEP § 716.07). A showing sufficient to overcome the presumption of operability and enablement is discussed at MPEP § 716.07. All arguments premised upon the declaration have been addressed once in a separate section, below, which directly addresses the declaration. In brief, the declaration is insufficient to satisfy MPEP § 716.02 or § 716.07 for reasons discussed below, and those reasons are incorporated into the instant response.
Allegations suggesting “skepticism of experts”: It is the Examiner’s understanding that Applicant’s statements amount to a suggestion that the Examiner’s position would be met with skepticism of experts (see, e.g., Reply filed 3/26/2026 at 12 at 3rd ¶, 13-14 at bridging ¶, passim). If Applicant means to suggest the existence of skepticism of experts, such evidence should be filed per MPEP § 716.05 as evidence is required to establish skepticism of experts. In the absence of such evidence, such statements are understood to be unsupported conjecture of counsel. The prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)), and no objective evidence rebutting this presumption has been placed on record to date.
Allegations suggesting “lack of predictability” or “lack of reasonable expectation of success”: It is the Examiner’s understanding that Applicant is alleging a lack of predictability or otherwise a lack of reasonable expectation of success (see, e.g., Reply filed 3/26/2026 at 12 at 3rd ¶, 13-14 at bridging ¶, passim). This is not persuasive because the Applicant’s assertions do not reflect the proper legal standards for evaluating predictability. MPEP § 2143.02(II) explains that “[o]bviousness does not require absolute predictability”, but instead clarifies that only “at least some degree of predictability is required” (see, e.g., MPEP § 2143.02(II)). Here, the rejection explicitly addresses predictability and reasonable expectation of success, but Applicant fails to address the explicitly identified predicted and expected results set forth in the rejection. Here, the Examiner’s basis for “predictability” is merely based upon the presumption that the prior art is fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). As explained at MPEP § 2143.02, predictability and reasonable expectation of success are satisfied when “all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art”. Here zero evidence of unexpected results commensurate in scope with the requirements of MPEP 716.02 have been set forth on record, all elements of the claimed invention were known in the prior art, one of ordinary skill was fully enabled to combined each component using routine methods in the biochemical arts per the guidance of the primary reference, and the elements would have merely performed their art-recognized, respective functions (see Rejection, above). Accordingly, such arguments are not persuasive.
Allegations suggesting improper or impermissible hindsight: It is the Examiner’s understanding that Applicant is suggesting that the Examiner’s position fails to establish a prima facie case of obviousness because the prior art does not lead an artisan to the instant invention (see, e.g., Reply filed 3/26/2026 at 13 at 2nd full ¶). If Applicant means to suggest that the Examiner arrived at the instantly claimed invention via the use of improper hindsight, this is not persuasive because any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Here, Applicant fails to identify a single aspect of the claimed invention that was not explicitly taught, disclosed, or suggested by the prior art relied upon by the Examiner, and merely performs anything other than its art-recognized function.
No evidence of unexpected results or criticality of range has been placed on record: To date, zero evidence of unexpected results sufficient to rebut prima facie obviousness and commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 has been placed on record. No evidence showing criticality of range commensurate with the requirements of MPEP § 716.02(d) has been placed on record as not data of record is shown to be of statistical significance as required by MPEP § 716.02(b) and is also commensurate in scope with the open-ended claims (see, e.g., MPEP § 716.02(d)). Rather the instant claims achieve the predicted and expected result taught and suggested by the prior art (i.e., injectable pharmaceutical compositions of a known peptide), and therefore evidence confirming the expectations of the prior art actually weigh in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)).
Therefore, in view of the totality of all evidence of record, the claimed invention is understood to be obvious for reasons of record. Examination has not yet proceeded to any non-elected species.
Arguments Regarding Nonstatutory Double Patenting Rejections
It is the Examiner’s understanding that Applicant traverses the Nonstatutory Double Patenting Rejections at 13-14 (see, e.g., Reply filed 3/26/2026 at 13 at § “Obviousness-Type Double Patenting Rejection” to page 14 at 1st full ¶).
It is the Examiner’s understanding that Applicant reiterates arguments under 35 USC 103 and requests that the rejection be held in abeyance (see, e.g., Reply filed 3/26/2026 at 13 at final ¶, 14 at 1st full ¶). All arguments under 35 USC 103 have been fully considered, but not found persuasive for reasons set forth above, which are incorporated herein. Regarding abeyance, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02), and requires a proper response. A proper response includes a Terminal Disclaimer approved by the Office, amendment to distinguish from the reference patent, or persuasive arguments as to why the rejection is incorrect. Accordingly, the rejection is maintained.
Summary
All arguments raised by the Applicant have been fully considered but not found persuasive as explained above. Accordingly, the rejections are maintained as revised above. The revisions were necessitated by Applicant amendment or otherwise to correctly withdraw claims not directed to the originally elected species. The citations and rationales supporting a determination of allowability have not been altered.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
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, Lianko G. Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/RANDALL L BEANE/Primary Examiner, Art Unit 1654
1 This buffer is understood to comprise citric acid hydrate and sodium citrate hydrate, dissolved in water, and mixed to obtain a predetermined concentration.
2 As explained above, and understood in view of Applicant’s arguments regarding claim interpretation as filed 3/26/2026, claims 1-4 and 11-13 were improperly included in Examination in the previous action, and do not read upon the originally elected species of injectable, aqueous formulation set forth at Example 1. The instant action corrects this issue by withdrawing claims 1-4 and 11-13.
3 See, e.g., MPEP § 2113(I), noting that "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)
4 See, e.g., Spec. filed 10/19/2022 at ¶[0111] at page 23 at Table 1.
5 See, e.g., Reply filed 3/26/2026 at 6-7 at § Claim Interpretation.
6 See prior footnote.
7 This buffer is understood to comprise citric acid hydrate and sodium citrate hydrate, dissolved in water, and mixed to obtain a predetermined concentration.
8 Nuijen et al., Development of a lyophilized parenteral pharmaceutical formulation of the investigational polypeptide marine anticancer agent kahalalide F. Drug Dev Ind Pharm. 2001 Sep;27(8):767-80. doi: 10.1081/ddc-100107240. PMID: 11699828; hereafter “Nuijen”; cited in previous action.
9 Nuijen et al., Development of a lyophilized parenteral pharmaceutical formulation of the investigational polypeptide marine anticancer agent kahalalide F. Drug Dev Ind Pharm. 2001 Sep;27(8):767-80. doi: 10.1081/ddc-100107240. PMID: 11699828; hereafter “Nuijen”; cited in previous action.
10 Rowe et al., Handbook of Pharmaceutical Excipients, 6th Ed., 917 pages, Published by Pharmaceutical Press 2009, excerpt of title, table of contents at i-viii, and pages 181-183, 549-553, 640-642, 648-649; hereafter “Rowe”; cited in previous action.
11 Nuijen et al., Development of a lyophilized parenteral pharmaceutical formulation of the investigational polypeptide marine anticancer agent kahalalide F. Drug Dev Ind Pharm. 2001 Sep;27(8):767-80. doi: 10.1081/ddc-100107240. PMID: 11699828; hereafter “Nuijen”; cited in previous action.
12 Rowe et al., Handbook of Pharmaceutical Excipients, 6th Ed., 917 pages, Published by Pharmaceutical Press 2009, excerpt of title, table of contents at i-viii, and pages 181-183, 549-553, 640-642, 648-649; hereafter “Rowe”; cited in previous action.
13 Shalaev et al., Thermophysical properties of pharmaceutically compatible buffers at sub-zero temperatures: implications for freeze-drying. Pharm Res. 2002 Feb;19(2):195-201. doi: 10.1023/a:1014229001433. PMID: 11883647; hereafter “Shalaey”; cited in previous action.
14 Nuijen et al., Development of a lyophilized parenteral pharmaceutical formulation of the investigational polypeptide marine anticancer agent kahalalide F. Drug Dev Ind Pharm. 2001 Sep;27(8):767-80. doi: 10.1081/ddc-100107240. PMID: 11699828; hereafter “Nuijen”.
15 Nuijen et al., Development of a lyophilized parenteral pharmaceutical formulation of the investigational polypeptide marine anticancer agent kahalalide F. Drug Dev Ind Pharm. 2001 Sep;27(8):767-80. doi: 10.1081/ddc-100107240. PMID: 11699828; hereafter “Nuijen”.
16 This patent corresponds to US 2015/0274792A1 as applied under 35 USC 103, above.
17 Nuijen et al., Development of a lyophilized parenteral pharmaceutical formulation of the investigational polypeptide marine anticancer agent kahalalide F. Drug Dev Ind Pharm. 2001 Sep;27(8):767-80. doi: 10.1081/ddc-100107240. PMID: 11699828; hereafter “Nuijen”; cited in previous action.
18See, e.g., Reply filed 3/26/2026 at 6-7 at § Claim Interpretation.
19 The reply states that “The claim language does not recite a hypothetical, optional, or incidental condition…”
20 See, e.g., Spec. filed 10/19/2022 at ¶[0111] at page 23 at Table 1.
21 Nuijen et al., Development of a lyophilized parenteral pharmaceutical formulation of the investigational polypeptide marine anticancer agent kahalalide F. Drug Dev Ind Pharm. 2001 Sep;27(8):767-80. doi: 10.1081/ddc-100107240. PMID: 11699828; hereafter “Nuijen”; cited in previous action.
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